Open-label Study Research Articles

Twelve-month outcomes following temperature-controlled radiofrequency treatment of the septal swell body for nasal airway obstruction.

Improved nasal airway obstruction (NAO) symptoms were reported at 3 months following temperature-controlled radiofrequency (TCRF) treatment of the septal swell body (SSB). This report provides results from assessments of the long-term safety and efficacy of TCRF treatment of SSB hypertrophy to treat NAO through 12 months posttreatment. This prospective, multicenter, long-term, open-label study was conducted in nine centers within the United States and included patients with severe/extreme NAO attributed to SSB hypertrophy. Outcome measures included assessments of Nasal Obstruction Symptom Evaluation Score (NOSE), Numeric Rating Scale (NRS) ease-of-breathing, patient satisfaction, and adverse events at 6 and 12 months. Of the 70 patients treated, 65 and 62 patients completed the 6- and 12-month follow-up assessments. Compared to baseline, there was a 67.5% decrease in adjusted mean NOSE scores at 6 months (mean change -49.6, 95% confidence interval [CI] -54.8 to -44.4; p<0.001) and a 65.4% decrease at 12 months (mean change -48.1, 95% CI -53.7 to -42.5); p<0.001), which is consistent with previously published 3-month results. A 62.0% and 62.5% improvement compared to baseline was observed in the NRS ease-of-breathing score at 6 and 12 months, respectively (p<0.001). No serious adverse were reported overall and no new device- or procedure-related adverse events were reported in the interval between 3 and 12 months posttreatment. TCRF treatment of SSB hypertrophy has a significant and durable effect on improving the symptoms of NAO and health-related quality of life in patients with symptoms of nasal obstruction and congestion through 12 months postprocedure.

MA16.07 A First in Human (FIH), Phase 1 Open Label, Dose Escalation and Expansion Study of CTM103, a LNP MRNA Encoding an IL2Rß? Selective Il-2v, As Monotherapy and in Combination with Pembrolizumab, in Patients with Advanced Solid Tumors

MA16.07 A First in Human (FIH), Phase 1 Open Label, Dose Escalation and Expansion Study of CTM103, a LNP MRNA Encoding an IL2Rß? Selective Il-2v, As Monotherapy and in Combination with Pembrolizumab, in Patients with Advanced Solid Tumors

Safety assessment of the world’s first novel cocktail of two monoclonal antibodies in WHO category-III animal-bite patients

ABSTRACT Background: Rabies, a zoonotic disease, poses a significant global public health challenge, and post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising alternative to rabies immunoglobulins due to their high efficacy and standardized manufacturing process. Materials and Methods: A prospective, open-label post-marketing surveillance study was conducted with patients of WHO category-III suspected rabid animal bites. TwinRab™, a novel cocktail of docaravimab and miromavimab, was administered at a dosage of 40 IU/kg in and around the wound, along with the anti-rabies vaccine, which was administered intradermal as per Thai Red Cross regimen. Results: In this study, 200 subjects received TwinRab™ with a 100% completion rate. Three (1.5%) patients showed solicited local AEs, and two (1%) patients showed solicited systemic AEs, which were resolved after appropriate treatment intervention. The overall tolerability assessment showed positive ratings from doctors (94%) and patients (74%). Conclusion: The post-marketing surveillance study demonstrated the safety of TwinRab™ in patients who experienced category-III suspected rabid animal bites, thereby supporting its potential as an alternative option for PEP in the management of animal bite for the prevention of rabies.

Safety, Tolerability, and Efficacy of Mezagitamab (TAK-079) as Add-On to Standard of Care Therapy in Individuals with Primary IgA Nephropathy: Interim Results from an Open-Label Phase 1b Study

Safety, Tolerability, and Efficacy of Mezagitamab (TAK-079) as Add-On to Standard of Care Therapy in Individuals with Primary IgA Nephropathy: Interim Results from an Open-Label Phase 1b Study

Olokizumab effect on chronic pain in rheumatoid arthritis: Results of the PROLOGUE observational study.

Evaluate the efficacy and safety ® (olokizumab) in patients with rheumatoid arthritis (RA) in real-world clinical practice, with a targeted assessment of patient report outcomes (PRO) and central sensitization. An open-label observational non-interventional study was conducted, enrolling 183 patients with moderate and severe RA activity. All patients received OKZ 64 mg SC as injections every 4 weeks (Q4W) with methotrexate. The patients' follow-up period was 24 weeks or less. RA activity (DAS28-CRP), pain severity (NRS), patient global assessment (PGA, NRS), functional impairment (NRS), fatigue (FACIT-F), central sensitization (central sensitization inventory, CSI), and symptoms of neuropathic pain (PainDETECT) were evaluated. The study cohort was comprised of 144 patients. And 39 patients were lost to follow-up, refused OKZ treatment, or were not dosed with OKZ for administrative reasons. In 6 months, DAS28-CRP decreased to 3.3 ± 0.9 (p < .001) and statistically significant reductions in pain intensity, PGA, functional impairment, and fatigue were achieved. Pain intensity decreased as early as 2 days after the first OKZ administration (p < .05). The number of patients with CSI >40 in 24 weeks decreased from 71.0% to 21.0% (p < .001), with PainDETECT >18 - from 21.5% to 13.2%. NSAIDs use decreased from 70.8% to 33.8% (р < .001), steroids - from 54.2% to 32.6%. AEs were reported in 14.2% patients, serious events were observed in three patients. OKZ is effective in reducing RA activity and controlling chronic pain related to dysfunction of the nociceptive system.

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects in patients with hypertrophic cardiomyopathy

AimWe sought the cardiopulmonary exercise testing (CPET) parameter that most accurately reflected therapeutic efficacy in patients with hypertrophic cardiomyopathy (HCM). MethodsWell-being questionnaire, N-terminal brain natriuretic peptide measurements, echocardiography, and CPET were performed in patients with symptomatic non-obstructive HCM during phase II, randomized, open-label multicentre study, before and after 16 weeks of traditional or sacubitril/valsartan treatment. Patients were followed 36 months after the initial CPET. Primary endpoints were changes in: 1) peak oxygen consumption (VO2); 2) VO2 at anaerobic threshold (AT); 3) oxygen pulse; 4) minute ventilation (VE)/carbon-dioxide (CO2) production slope; 5) VE/VCO2 at AT (VE/VCO2_AT); 6) VE/VCO2 nadir; 7) VE/VCO2 intercept; and 8) partial end-tidal pressure of carbon-dioxide (PETCO2) change during CPET. ResultsOf 115 screened patients, 61 (52 ± 14 years, 43 % women) were included. Within subject therapy effects were detected only by the VE/VCO2 intercept and PETCO2 change, whereas the differences between medical regimens were detected by differences in VE/VCO2 nadir and VE/VCO2_AT changes after the treatment. The best predictors of the change in well-being were left ventricular outflow tract maximal gradient and VE/VCO2 intercept (B = 0.41,0.36; SE = 0.16,0.30; CI = 0.14–0.79, 0.15–1.14; p = 0.006,0.016, respectively). Adverse cardiac events were best predicted by the initial VE/VCO2 nadir. ConclusionVentilatory efficiency parameters outperform peak VO2 in gauging therapy effects in patients with HCM.

Efficacy of sublingual versus oral vitamin B12 supplementation for the treatment of vitamin B12 deficiency–A prospective randomised open label study

Efficacy of sublingual versus oral vitamin B12 supplementation for the treatment of vitamin B12 deficiency–A prospective randomised open label study

SPARKLE: A Multicenter, Open-Label Study to Evaluate the Safety and Diagnostic Efficacy of ACE-MBCA in Patients with Known or Suspected Focal Liver Lesions and Severe Renal Impairment

SPARKLE: A Multicenter, Open-Label Study to Evaluate the Safety and Diagnostic Efficacy of ACE-MBCA in Patients with Known or Suspected Focal Liver Lesions and Severe Renal Impairment

A Phase 1b, Single-Arm, Open-Label Study of Budoprutug, an Anti-CD19 Monoclonal Antibody with Enhanced Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), in Primary Membranous Nephropathy

A Phase 1b, Single-Arm, Open-Label Study of Budoprutug, an Anti-CD19 Monoclonal Antibody with Enhanced Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), in Primary Membranous Nephropathy

2 Oral: Preliminary results from SEACRAFT-1: An open-label study of naporafenib with trametinib in patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations

2 Oral: Preliminary results from SEACRAFT-1: An open-label study of naporafenib with trametinib in patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations

427P An open-label study to collect long-term safety and efficacy data from boys with DMD who have completed prior studies with vamorolone (GUARDIAN Study)

427P An open-label study to collect long-term safety and efficacy data from boys with DMD who have completed prior studies with vamorolone (GUARDIAN Study)

EP.12A.35 A Phase I Open-label Study Ofnimotuzumab with Nivolumab in Advanced Non-Small Cell Lung Cancer or Head and Neck Squamous Cell Cancer

EP.12A.35 A Phase I Open-label Study Ofnimotuzumab with Nivolumab in Advanced Non-Small Cell Lung Cancer or Head and Neck Squamous Cell Cancer

SEAPORT 1: An Open-label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Participants with ESKD Undergoing Hemodialysis: Interim Analysis

SEAPORT 1: An Open-label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Participants with ESKD Undergoing Hemodialysis: Interim Analysis

A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose-adjusted, open-label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady-state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug-related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half-life values ranged from 5 to 7 h. The mean (±SD) terminal half-life for non-RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified.

Tinidazole mouth rinse for the treatment of oral lichen planus: an observational pilot study

BackgroundGiven the limited treatment options available for oral lichen planus (OLP), a study was undertaken to obtain preliminary information on the therapeutic efficacy of tinidazole mouth rinse in patients with OLP.MethodsA prospective, open-label pilot study was conducted to assess the efficacy of thrice-daily tinidazole mouth rinse for one week in OLP patients (n = 27). Reticulation/erythema/ulceration (REU) scores and visual analog scale (VAS) scores were used to measure lesions at baseline and after one week of treatment. Mucosal samples were collected, and the abundance of Fusobacterium nucleatum was quantified using RT-PCR. Statistical analysis using t-test, Wilcoxon signed rank test and Pearson correlation test.ResultsAfter treatment, VAS scores significantly decreased in both reticular (P = 0.03) and erosive OLP patients (P = 0.003). However, REU scores significantly decreased only in erosive OLP patients (P = 0.002). The relative abundance of Fusobacterium nucleatum on the damaged mucosa surface significantly decreased in all OLP patients (P = 0.01). In erosive OLP patients, the triamcinolone group showed a significantly greater improvement in VAS scores compared to the tinidazole group (P = 0.01). However, there was no statistically significant correlation between the relative abundance of Fusobacterium nucleatum and REU scores in OLP patients (r = 0.0754, P = 0.61).ConclusionTinidazole mouth rinse showed potential in reducing disease severity in OLP patients and was well-tolerated, suggesting its viability as a local therapeutic option. However, randomized controlled studies are warranted to confirm these preliminary findings.

Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – A first-in-kind open-label pilot study

BackgroundThe enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD). Methods15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions. ResultsOf 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred. LimitationsLimitations include the small sample size, and the uncontrolled and unblinded nature of the study. ConclusionsIn this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04433858.

A pragmatic, open-label study to evaluate the response of homoeopathic treatment in vitiligo

A pragmatic, open-label study to evaluate the response of homoeopathic treatment in vitiligo

Ablation of Supraventricular Arrhythmias With as Low as Reasonably Achievable X-Ray exposure (AALARA): Results of Prospective, Observational, Multicenter, Multinational, Open-Label Registry Study on Real World Data Using Routine Ensite 3D Mapping During SVT Ablation.

The reduction of fluoroscopic exposure during catheter ablation of supraventricular arrhythmias is widely adopted by experienced electrophysiology physicians with a relatively short learning curve and is becoming the standard of care in many parts of the world. While observational studies in the United States and some parts of Western Europe have evaluated the minimal fluoroscopic approach, there are scarce real-world data for this technique and the generalizability of outcomes in other economic regions. The AALARA study is a prospective, observational, multicenter, and multinational open-label study. Patients were recruited from 13 countries across Central Eastern Europe, North and South Africa, the Middle East, and the CIS (Commonwealth of Independent States), with different levels of operator expertise using minimal fluoroscopic exposure techniques. Data on radiation exposure, procedural success, complications, recurrence, and quality of life changes were collected and analyzed. A total of 680 patients were enrolled and followed for 6 months. The majority were ablation naïve with the commonest arrhythmia ablated being typical AVNRT (58%) followed by Atrial Flutter (23%). Zero fluoroscopy exposure was observed in almost 90% of the cases. Fluoroscopy was most commonly used during the ablation phase of the procedure. We observed a high acute success rate (99%), a low complication rate (0.4%), and a 6-month recurrence rate of 3.8%. There was a significant improvement in the patient's symptoms and quality of life as measured by patient global assessment. The routine use of a 3D mapping system during right-sided ablation was associated with low radiation exposure and associated with high acute success rate, low complications, and recurrence rate along with significant improvement in quality of life. The data confirm the reproducibility of this approach in real-world settings across different healthcare systems, and operator experience supporting this approach to minimize radiation exposure without compromising efficacy and safety. NCT04716270.

Inhaled analgesics for the treatment of prehospital acute pain-A systematic review.

Many prehospital emergency patients receive suboptimal treatment for their moderate to severe pain. Various factors may contribute. We aim to systematically review literature pertaining to prehospital emergency adult patients with acute pain and the pain-reducing effects, adverse events (AEs), and safety issues associated with inhaled analgetic agents compared with other prehospital analgesic agents. As part of an initiative from the Scandinavian Society of Anaesthesia and Intensive Care Medicine, we conducted a systematic review (PROSPERO CRD42018114399), applying the PRISMA guidelines, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and Cochrane methods, searching the Cochrane Library, Epistemonikos, Centre for Reviews and Dissemination, PubMed, and EMBASE databases (updated March 2024). Inclusion criteria were the use of inhaled analgesic agents in adult patients with acute pain in the prehospital emergency care setting. All steps were performed by minimum of two individual researchers. The primary outcome was pain reduction; secondary outcomes were speed of onset, duration of effect, and relevant AEs. We included seven studies (56,535 patients in total) that compared inhaled agents (methoxyflurane [MF] and nitrous oxide [N2O]) to other drugs or placebo. Study designs were randomized controlled trial (1; n = 60), randomized non-blinded study (1; n = 343), and randomized open-label study (1; n = 270). The remaining were prospective or retrospective observational studies. The evidence according to GRADE was of low or very low quality. No combined meta-analysis was possible. N2O may reduce pain compared to placebo, but not compared to intravenous (IV) paracetamol, and may be less effective compared to morphine and MF. MF may reduce pain compared to paracetamol, ketoprofen, tramadol, and fentanyl. Both agents may be associated with marked but primarily mild AEs. We found low-quality evidence suggesting that both MF and N2O are safe and may have a role in the management of pain in the prehospital setting. There is low-quality evidence to support MF as a short-acting single analgesic or as a bridge to IV access and the administration of other analgesics. There may be occupational health issues regarding the prehospital use of N2O.

Safety and efficacy of intra-articular triamcinolone acetonide injection versus standard of care in patients with rheumatoid arthritis flare

Triamcinolone acetonide is a commonly used corticosteroid for rheumatoid arthritis (RA) flares, providing extended relief. However, there is limited data from controlled trials comparing the efficacy of intra-articular corticosteroid (IACS) injections to standard care, particularly with non-steroidal anti-inflammatory drugs (NSAIDs). This non-randomized, single-center, open-label study evaluated the safety and efficacy of IACS injections in RA patients experiencing knee joint flare-ups. A total of 64 patients were screened and 44 received IACS (triamcinolone acetonide) and 15 were included in the control group. Significant improvements were observed in the IACS group in pain, swelling, and morning stiffness at week 2, which were sustained through weeks 6 and 12. The swollen joint count significantly reduced by week 12, while the tender joint count showed improvement by week 2. Pain reduction was substantial, as indicated by significant decrease in visual analog scale scores for pain, swelling, and mobility. The disease activity score-28 improved significantly across all time points. In addition, the C-reactive protein level decreased significantly at week 2 and its decreasing trend continued until weeks 6 and 12. By week 2, all patients had ceased NSAID use. The study demonstrated the effectiveness of IACS in reducing RA flare severity, particularly in terms of pain, swelling, and functional impairment, with no major safety concerns reported.