Injection-site Adverse Events Research Articles

Safe and Effective Restoration of Jawline Definition With Hyaluronic Acid Injectable Gel VYC-25L: Results From a Randomized Controlled Study.

A well-defined jawline improves overall facial aesthetics, thus motivating patients to seek jawline augmentation. This study will evaluate the safety and effectiveness of the hyaluronic acid injectable gel VYC-25L for restoring jawline definition. A US multicenter, evaluator-blinded study randomized adults with grade 2 (moderate) or 3 (severe) Allergan Loss of Jawline Definition Scale (ALJDS) scores. Participants were randomized to VYC-25L treatment group or control group at study onset, with 12 months follow-up. The control group had the option to receive treatment after 6 months (primary endpoint completion). Effectiveness measures included month 6 ALJDS responders rate (proportion of participants with ≥1-grade improvement from baseline on both sides), FACE-Q Satisfaction With Lower Face and Jawline scores, and Global Aesthetic Improvement Scale (GAIS) responders (improved/much improved) as assessed by the investigator and participants. Injection site responses (ISRs) and adverse events (AEs) were monitored. At month 6, ALJDS responder rates were 69.0% versus 38.0% in the VYC-25L treatment (n = 157) and control (n = 49) groups, respectively (p = .0001). In the VYC-25L treatment group, FACE-Q scores improved by a mean of 45.9 points versus baseline at month 6 (p < .0001). Furthermore, 88.4% and 89.0% of participants in the VYC-25L treatment group were GAIS responders on month 6 by participant- and investigator-assessment, respectively. Most ISRs were mild or moderate and resolved within 2 weeks. Most treatment-related AEs were mild and resolved within a week. VYC-25L safely and effectively restores jawline definition through 1 year.

A 12-Month Analysis of the Dermatologic Effects and Durability of Midface Volume Correction With DEFCL Volumizing Filler in a Prospective, Single-Center Study.

Certain manufacturing processes confer distinctive rheologic features to hyaluronic acid (HA), ensuring long-lasting effects. Skin quality improvement and the volumizing effects of the DEFCL volumizer filler, a sterile, biodegradable, viscoelastic, transparent, isotonic, and homogenized injectable cross-linked high G' filler for the treatment of moderate-to-severe age-related midface changes, were initially documented at 6 months after the first injection. The authors aimed to objectively evaluate the effects of the DEFCL volumizer filler in improving skin density, thickness, and biomechanical properties and on tissue volume augmentation in women with midface volume loss after 12 months. Fifty women with midface volume loss were recruited in this prospective, noncomparative, single-center, postmarket study. The authors report changes in skin density, thickness, and quality and subjective and objective evaluation of facial and/or cheek volume augmentation using the Global Aesthetic Improvement Scale, as well as injection site reactions and adverse events. Improvements in skin quality and thickness and volumization were maintained 12 months after the first injection. Injector and patient satisfaction were highly rated with only mild adverse reactions observed. Skin improvement and volumizing effects persisted in patients treated with the DEFCL volumizer after 12 months.

Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study.

BackgroundNon-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.AimTo describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.MethodsParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021-November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.ResultsWe received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23-1.54).ConclusionsOur study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.

Cutaneous adverse events following COVID-19 vaccination: A case series of 30 Japanese patients and a review of 93 Japanese studies.

In Japan, cutaneous adverse events (AEs) following the coronavirus disease 2019 (COVID-19) vaccination have been frequently described; however, a larger case series and literature review are lacking. There is an urgent need for an extensive investigation of new cases and previous reports to provide a thorough body of information about post-COVID-19 immunization cutaneous AEs. We aimed to analyze patients with cutaneous AEs after COVID-19 vaccination in our hospital and review previous studies of cutaneous AEs. We analyzed post-COVID-19 vaccination cutaneous AEs in our department, the Japanese Registry, and previous literature. We enrolled 30 patients with cutaneous post-vaccination AEs in our department over 2 years (April 1, 2021, to March 31, 2023). We also confirmed cases registered in the Ministry of Health, Labor, and Welfare COVID-19 vaccine side effect reporting system (February 17, 2021-March 12, 2023). A total of 587 records were retrieved and 93 articles were included for data extraction. A total of 28 non-injection-site cutaneous AEs and two injection-site AEs were identified. Six (20.0%) patients developed new-onset erythematous eruptions, and five (16.7%) patients developed urticaria. Pruritic eruption, eczema, shingles, and sweating symptoms have also been reported. In previous studies on non-injection-site cutaneous AEs, individuals who received the BNT162b2 vaccine were older than those who received mRNA-1273 (P < 0.01). Cutaneous AEs were mostly nonsignificant and self-limiting reactions; however, rare, severe, or life-threatening AEs were also reported. Physicians should be aware of the various possible cutaneous AEs associated with the COVID-19 vaccination.

Listing and Comparing the Immunogenicity, Safety, and Effectiveness of 9vHPV Vaccinations for Different Age Groups: 9-15 Years Old, 16-26 Years Old, 27-45 Years Old

The effectiveness of the Human Papillomavirus (HPV) vaccination in preventing high-risk HPV infections and accompanying serious vaginal, cervical, and vulvar disorders was verified. The development of the 9-valent HPV(9vHPV) vaccine yields greater coverage versus the quadrivalent (qHPV) vaccine. This study aims to assess the 9vHPV from immunogenicity, safety, and effectiveness in three different age groups respectively: 9-15 years old, 16-26 years old, and 27-45 years old. This paper searched PubMed and Embase databases to include related clinical trials of these three age groups and ensure a large-scale study population. Immunogenicity analysis for different age groups reported that the geometric mean titers (GMTs) decreased with age but could still stimulate robust and effective immune responses. The antibody levels of the subjects significantly increased to reach protective levels and persisted for a long time after vaccination. Besides, the 9vHPV vaccine has a high protective effect against the infection of nine subtypes of HPV. Both HPV infection rates and rates of associated diseases significantly decreased versus those who did not receive the vaccine. Additionally, the outcomes also demonstrated that the safety of the 9vHPV vaccines was good across all age groups. The intensity of most reported injection-site adverse events (AEs) and vaccine-related systemic AEs were not serious. Serious adverse reactions are very rare. In total, immunogenicity, efficacy, and safety in different age groups of the 9vHPV vaccination are overall good. These findings provide scientific evidence for the immunization of the 9vHPV vaccine and recommend the optimal age for vaccination.

Safety, efficacy, and immunogenicity of a replication-defective human cytomegalovirus vaccine, V160, in cytomegalovirus-seronegative women: a double-blind, randomised, placebo-controlled, phase 2b trial

A vaccine that prevents cytomegalovirus (CMV) infection in women could reduce the incidence of congenital CMV infection, a major cause of neurodevelopmental disability. We aimed to assess the safety and efficacy of a replication-defective investigational CMV vaccine, V160, in CMV-seronegative women. This phase 2b, randomised, double-blind, placebo-controlled study was conducted at 90 sites in seven countries (USA, Finland, Canada, Israel, Spain, Russia, and Australia). Eligible participants were generally healthy, CMV-seronegative, non-pregnant, 16-35-year-old women of childbearing potential with exposure to children aged 5 years or younger. Participants were randomly assigned using central randomisation via an interactive response technology system 1:1:1 to one of three groups: V160 three-dose regimen (V160 at day 1, month 2, and month 6), V160 two-dose regimen (V160 on day 1, placebo at month 2, and V160 at month 6), or placebo (saline solution at day 1, month 2, and month 6). The primary outcomes were the efficacy of three doses of V160 in reducing the incidence of primary CMV infection during the follow-up period starting 30 days after the last dose of vaccine using a fixed event rate design, and the safety and tolerability of the two-dose and three-dose V160 regimens. We planned to test the efficacy of a two-dose regimen of V160 in reducing the incidence of primary CMV infection only if the primary efficacy hypothesis was met. Analyses for the primary efficacy endpoint were performed on the per-protocol efficacy population; safety analyses included all randomly assigned participants who received study vaccine. The primary efficacy hypothesis was tested at prespecified interim and final analyses. The study was ongoing and efficacy data continued to accrue at the time of final testing of the primary efficacy hypothesis. Vaccine efficacy was re-estimated after final testing of the primary efficacy hypothesis based on all available efficacy data at end of study. This trial is registered at ClinicalTrials.gov (NCT03486834) and EudraCT (2017-004233-86) and is complete. Between April 30, 2018, and Aug 30, 2019, 7458 participants were screened, of whom 2220 were randomly assigned to the V160 three-dose group (n=733), V160 two-dose group (n=733), or placebo group (n=734). A total of 523 participants in the V160 three-dose group and 519 in the placebo group were included in the final hypothesis testing. Of these, there were 11 cases of CMV infection in the V160 three-dose group and 20 cases in the placebo group. The vaccine efficacy for the V160 three-dose group was 44·6% (95% CI -15·2 to 74·8) at the final testing of the primary efficacy hypothesis, a result corresponding to failure to demonstrate the primary efficacy hypothesis. On the basis of this result, the study was terminated for futility. The re-estimate of vaccine efficacy for the V160 three-dose group based on all available efficacy data at end of study (556 participants in the V160 three-dose group and 543 in the placebo group) was 42·4% (95% CI -13·5 to 71·1). A total of 728 participants in the V160 three-dose group, 729 in the V160 two-dose group, and 732 in the placebo group were included in the safety analyses. The most common solicited injection-site adverse event was injection-site pain (680 [93%] in the V160 three-dose group, 659 [90%] in the V160 two-dose group, and 232 [32%] in the placebo group). The most common solicited systemic adverse event was fatigue (457 [63%] in the V160 three-dose group, 461 [63%] in the V160 two-dose group, and 357 [49%] in the placebo group). No vaccine-related serious adverse events or deaths were reported. V160 was generally well tolerated and immunogenic; however, three doses of the vaccine did not reduce the incidence of primary CMV infection in CMV-seronegative women compared with placebo. This study provides insights into the design of future CMV vaccine efficacy trials, particularly for the identification of CMV infection using molecular assays. Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial

Cabotegravir plus rilpivirine is the only approved complete long-acting regimen for the maintenance of HIV-1 virological suppression dosed every 2 months. The SOLAR study aimed to compare long-acting cabotegravir plus rilpivirine every 2 months with continued once-daily bictegravir, emtricitabine, and tenofovir alafenamide for the maintenance of HIV-1 virological suppression in adults living with HIV. SOLAR is a randomised, open-label, multicentre, phase 3b, non-inferiority study. The study was done in 118 centres across 14 countries. Participants with HIV-1 RNA less than 50 copies per mL were randomly assigned (2:1), stratified by sex at birth and BMI, to either long-acting cabotegravir (600 mg) plus rilpivirine (900 mg) dosed intramuscularly every 2 months or to continue daily oral bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants randomly assigned to long-acting therapy had a choice to receive cabotegravir (30 mg) plus rilpivirine (25 mg) once daily as an optional oral lead-in for approximately 1 month. The primary efficacy endpoint was the proportion of participants with virological non-response (HIV-1 RNA ≥50 copies per mL; the US Food and Drug Administration snapshot algorithm, 4% non-inferiority margin; modified intention-to-treat exposed population) at month 11 (long-acting start with injections group) and month 12 (long-acting with oral lead-in group and bictegravir, emtricitabine, and tenofovir alafenamide group). The study is registered with ClinicalTrials.gov, NCT04542070, and is ongoing. 837 participants were screened between Nov 9, 2020, and May 31, 2021, and 687 were randomly assigned to switch treatment or continue existing treatment. Of 670 participants (modified intention-to-treat exposed population), 447 (67%) switched to long-acting therapy (274 [61%] of 447 start with injections; 173 [39%] of 447 with oral lead-in) and 223 (33%) continued bictegravir, emtricitabine, and tenofovir alafenamide. Baseline characteristics were similar; median age was 37 years (range 18-74), 118 (18%) of 670 were female sex at birth, 207 (31%) of 670 were non-White, and median BMI was 25·9 kg/m2 (IQR 23·3-29·5). At month 11-12, long-acting cabotegravir plus rilpivirine showed non-inferior efficacy versus bictegravir, emtricitabine, and tenofovir alafenamide (HIV-1 RNA ≥50 copies per mL, five [1%] of 447 vs one [<1%] of 223), with an adjusted treatment difference of 0·7 (95% CI -0·7 to 2·0). Excluding injection site reactions, adverse events and serious adverse events were similar between groups. No treatment-related deaths occurred. More long-acting group participants had adverse events leading to withdrawal (25 [6%] of 454 vs two [1%] of 227). Injection site reactions were reported by 316 (70%) of 454 long-acting participants; most (98%) were grade 1 or 2. These data support the use of long-acting cabotegravir plus rilpivirine dosed every 2 months as a complete antiretroviral regimen that has similar efficacy to a commonly used integrase strand transfer inhibitor-based first-line regimen, while addressing unmet psychosocial issues associated with daily oral treatment. ViiV Healthcare.

An Interim 6-Month Analysis of the Dermatologic Effects and Midface Volume Correction With XTR CL Filler in a Prospective, Single-Center Study.

Hyaluronic acid-based filler injections with parenteral anesthetics have become the standard in treating midface volume deficits. There are currently limited data on the effects of these types of fillers on skin density, thickness, and firmness. This study aimed to assess the efficacy of XTR CL filler in improving skin quality and tissue volume in women with midface volume loss. In this prospective, noncomparative, single-center study, 50 women aged between 40 and 60 years with midface volume loss were recruited. The primary endpoint was the improvement in investigator-assessed Global Aesthetic Improvement Scores (GAIS) 1 month after treatment. Secondary endpoints include objective measurements of skin density, thickness, and quality measurements, facial and/or cheek volume augmentation, subjective GAIS, and device evaluation from after the first injection until 6 months, and the documentation of injection site reactions and adverse events. XTR CL use led to significant improvement in midface volume deficits, and skin quality and skin thickness. Injector and subject satisfaction with the treatment were documented and only mild-to-moderate adverse reactions were reported. XTR CL was shown to be effective in improving volume loss and skin quality at 6 months.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

ABSTRACT This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20–45 years: A randomized, blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial

BackgroundHuman papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent). Methods1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20–26, 27–35, or 36–45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > −10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5. ResultsAmong the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded −10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths. ConclusionsThis study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.

Immunogenicity, durability, and safety of an mRNA and three platform-based COVID-19 vaccines as a third dose following two doses of CoronaVac in China: A randomised, double-blinded, placebo-controlled, phase 2 trial.

BackgroundMore effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines.MethodsThis randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 μg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 μg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 μg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758.FindingsBetween January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines.InterpretationAlthough all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant.FundingYunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Double First-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial

Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial

Timing and Location of Injection-site Adverse Events With Fremanezumab in Patients With Migraine: A Pooled Analysis of Phase 3 Studies (P16-2.003)

Timing and Location of Injection-site Adverse Events With Fremanezumab in Patients With Migraine: A Pooled Analysis of Phase 3 Studies (P16-2.003)

A Prospective, Open-Label, Multicenter, Real-World Study of VYC-17.5L Hyaluronic Acid Dermal Filler in the Lips.

BackgroundHyaluronic acid (HA) injectable gels are used to define, enhance, and volumize facial regions, such as the lips, a common treatment area.ObjectivesTo evaluate the effectiveness and safety of the HA injectable gel Juvéderm Volift (Allergan, Aesthetics, an AbbVie Company Irvine, CA) with Lidocaine (VYC-17.5L) for lip augmentation in real-world clinical practice.MethodsThis prospective, open-label, multicenter study initially designed for 6 months, then extended to 12 months, enrolled adults with an overall grade of minimal to moderate on the Lip Fullness Scale 2 (LFS2). Optional touch-up and repeat treatments occurred at day 14 and month 12, respectively. The primary endpoint was a ≥1-point improvement on the LFS2 at day 30. Other endpoints included improvements on the FACE-Q Satisfaction with Lips questionnaire, Global Aesthetic Improvement Scale (GAIS), subject assessment of natural look/feel of lips, and investigator assessment of dynamic lip lines upon animation. Injection site reactions (ISRs) and adverse events (AEs) were recorded.ResultsOf 60 subjects enrolled (mean age, 36.8 years; 98.3% female), 59 were evaluable for efficacy at day 30; 13 (21.4%) received touch-up treatment. Thirty-six of 40 subjects completed the extension study (month 12). LFS2 responder rates were 93.2% at day 30 (primary endpoint) and 39.0% at month 12. Mean scores on the FACE-Q questionnaire improved from baseline by 45.2 points and 23.6 points at day 30 and month 12, respectively. Most subjects showed improvements on the GAIS. The majority of ISRs were mild/moderate; no serious AEs occurred.ConclusionsVYC-17.5L was effective and well tolerated for lip augmentation through 12 months posttreatment.Level of Evidence: 4

Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial

BackgroundThe Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial.MethodsThis double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990).FindingsStudy enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7–70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36–58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients.InterpretationOne dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older.FundingCanSino Biologics and the Beijing Institute of Biotechnology.

API generation program: Active immunotherapy CAD106 slows amyloid deposition in cognitively unimpaired APOE4 homozygotes

AbstractBackgroundThe Alzheimer’s Prevention Initiative (API) Generation Study 1 (NCT0256551) evaluated CAD106, an active immunotherapy against Aβ, in delaying the clinical onset of Alzheimer’s disease in a cohort of cognitively unimpaired APOE4 homozygotes. Effect of CAD106 on brain amyloid burden after 2 years was measured by amyloid PET. Previous studies in mild AD showed that doses up to 450μg CAD106 induced sustained Aβ‐antibody response with no major safety concerns (Vandenberghe, 2017).MethodCognitively unimpaired APOE4 homozygotes age 60‐75 were enrolled using a 5:3 randomization ratio (CAD106 450μg:placebo). Intramuscular injections were administered at 0, 6, 12 weeks and then quarterly with alum as adjuvant. PET scans were conducted at baseline and 2 years mainly with florbetapir. Standard uptake value ratios (SUVRs) were calculated using cortical composite region in reference to cerebellum and converted to centiloids.ResultOut of 65 randomized participants (42:23 CAD106:placebo) 59 were followed for 18 months or longer. Mean age at baseline was 65 years, 68% were female. Mean baseline RBANS total score was 106. Year 2 PET scans were acquired in 35 CAD106 and 16 placebo participants with centiloid mean baseline of 49.5 (38.7).CAD106 induced measurable Aβ‐specific IgG titers in all treated participants. Mean (SD) annualized centiloid change from baseline was +8.4 (6.7) on placebo without change with CAD106 ((‐0.9 (5.7), p&lt;0.0001). The effect was more pronounced in amyloid positives: +9.4 (7.7) on placebo and ‐1.8 (6.0) with CAD106, vs in amyloid negatives: +6.7 (4.7) on placebo and +2.2 (2.8) with CAD106. In the CAD106 arm, the effect on PET correlated with antibody titers, especially for amyloid positive subgroup.Higher incidences for psychiatric (21% vs 13%) and general disorders / injection site (64% vs 22%) adverse events were reported with CAD106 vs placebo. Three cases of ARIA (2 ARIA‐H and 1 ARIA‐E) occurred on CAD106 (none on placebo). Cognition scores remained stable for 18 months in both groups.ConclusionCAD106 is the first active immunotherapy shown to slow amyloid deposition in humans. Treatment with CAD106 might have a positive risk/benefit profile for prevention of amyloid deposition in high‐risk populations.

Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, administered concomitantly with influenza vaccine in healthy adults aged ≥50 years: a randomized phase 3 trial (PNEU-FLU)

ABSTRACT Streptococcus pneumoniae and influenza viruses are associated with significant morbidity and mortality in older adults. Concomitant vaccination against these agents reduces hospitalization and mortality rates. This phase 3 trial evaluated safety, tolerability, and immunogenicity of concomitant and non-concomitant administration of V114, a 15-valent pneumococcal conjugate vaccine containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, 33F, and quadrivalent inactivated influenza vaccine (QIV), in healthy adults aged ≥50 years. Participants (N = 1,200) were randomized 1:1 to receive either V114 administered concomitantly with QIV (concomitant group) or QIV plus placebo (non-concomitant group) on Day 1, followed by placebo (concomitant group) or V114 (non-concomitant group) 30 days later. Randomization was stratified by age and history of pneumococcal polysaccharide vaccine receipt. Overall, 426 (71.0%) and 438 (73.5%) participants in the concomitant and non-concomitant groups experienced solicited injection-site adverse events (AEs); 278 (46.3%) and 300 (50.3%) reported solicited systemic AEs. Most solicited AEs were mild or moderate in severity and of short duration. Non-inferiority for pneumococcal- and influenza-specific antibody responses (lower bound 95% confidence interval of opsonophagocytic activity [OPA] and hemagglutination inhibition geometric mean titers [GMTs] ratios ≥0.5) was demonstrated for concomitant versus non-concomitant administration for all 15 pneumococcal serotypes and all four influenza strains. Consistent with previous studies, a trend was observed toward lower pneumococcal OPA GMTs in the concomitant versus the non-concomitant group. V114 administered concomitantly with QIV is generally well tolerated and immunologically non-inferior to non-concomitant administration, supporting coadministration of both vaccines.

Safety and efficacy of a carboxymethyl chitosan dermal injection device for the treatment of skin defects: a first-in-man, pilot, comparative, split-body study.

Injectable soft-tissue devices are increasingly used for improving skin defects and deficiencies related to ageing. To assess the safety and efficacy of KIO015, a new injectable soft-tissue device formulated with carboxymethyl chitosan for the intradermal treatment of skin defects associated with ageing. Twenty-two subjects (40-65 years) were randomized to receive injections in the neckline of KIO015 and a non-cross-linked HA-based device, and were followed for up to 10 months. Injection site reactions (ISRs) and adverse events (AEs) were documented. Skin improvement was assessed instrumentally and clinically. Skin biopsies at injection zones in the lower back were taken at Day 28 for histopathology and immunohistochemistry analyses, to further assess product performance. Histomorphometric analyses on rabbits and in vitro assessment of KIO015 antioxidant capacity were also conducted. KIO015 was very well tolerated. Only expected and transient ISRs were observed; mainly erythema and hematoma. No adverse local effects or foreign body granuloma were observed histologically. Both clinical and instrumental evaluations confirmed the performance of KIO015. The skin was firmer and more elastic. Skin hydration showed significant improvement three days after injection. KIO015 exhibited superior overall maintenance of skin hydration after 10 months as compared to HA. These clinical results were supported by in vitro trials and implantation tests in the rabbit. The results from this pilot study support the use of KIO015 as an innovative alternative to HA-based devices for intradermal treatment of skin disorders.

Effect of inclisiran on haematological and immunological biomarkers: A Pooled analysis of ORION-9, -10 and -11 trial data

Background and Aims: Haematological and immunological adverse effects and significant injection-site adverse events (AEs) have been reported with some early generation anti-sense oligonucleotide (RNA-based) therapies, which required frequent dosing and had non-specific organ uptake. Inclisiran is a novel small interfering RNA (siRNA) therapy with twice-yearly dosing, and conjugated with trivalent N-Acetylgalactosamine (GalNAc) enabling targeted hepatic delivery. Here, we assessed the effects of inclisiran on haematological and immunological biomarkers.

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in Vietnamese males and females (9 to 26 years of age): an open-label, phase 3 trial

ABSTRACT This open-label, single-center, Phase 3 study (NCT03546842) assessed the immunogenicity and safety of the nine-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine in Vietnamese males and females, with the aim to support 9vHPV vaccine licensure in Vietnam. Participants aged 9–26 years received three 9vHPV vaccine doses (Day 1, Month 2, Month 6). Serum samples were obtained on Day 1 (pre-vaccination) and at Month 7 (one month post-Dose 3) for the measurement of anti-HPV antibodies. Geometric mean titers (GMTs) and seroconversion percentages were obtained using the HPV-9 competitive Luminex immunoassay. Injection-site adverse events (AEs), systemic AEs, serious AEs (SAEs), and study discontinuations due to AEs were recorded. Of 201 participants enrolled, 200 (99.5%) received ≥1 vaccine dose. All participants who received the three-dose regimen (198/200, 98.5%) seroconverted for all 9vHPV vaccine types by Month 7. Robust anti-HPV GMT responses were also observed. Half of participants (50.5%) reported ≥1 AE; the majority were injection-site-related (45.0%) and mild (43.0%). There were no deaths, vaccine-related SAEs, or discontinuations due to AEs. Administration of three 9vHPV vaccine doses was highly immunogenic and resulted in acceptable seropositivity percentages for all vaccine HPV types. The 9vHPV vaccine was generally well tolerated among this study population. Region of origin: Vietnam Trial registration: clinicaltrials.gov Identifier NCT03546842