Harmonization Good Clinical Practice Research Articles

A phase 1/2 study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ.

TPS4626 Background: High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with adjuvant intravesical Bacille Calmette-Guérin (BCG). However, approximately 50% of patients experience recurrence and/or progression after BCG treatment and are considered unresponsive. EG-70 (detalimogene voraplasmid) is an investigational drug product that was specifically engineered for intravesical administration to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in patients with BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The phase 1 (dose-escalation) part of the first-in-human LEGEND (NCT04752722) phase 1/2, open-label, multicenter study of EG-70 in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) is complete: intravesical instillation of EG-70 was well tolerated with an overall complete response (CR) rate of 73%; and the recommended phase 2 dose (RP2D) was identified. Here we describe the ongoing phase 2 part of the study, which opened to enrollment in May 2023. Methods: Patient eligibility criteria: age ≥18 years; ECOG PS 0−2; BCG-unresponsive NMIBC with CIS, with or without resected coexisting papillary tumors, ineligible for, or have elected not to undergo, cystectomy; satisfactory bladder function with ability to retain study drug for ≥60 minutes. Prior checkpoint inhibitor treatment is allowed if completed within 30 days before study entry. Patients are treated with EG-70 at the RP2D (800 µg in 50 mL) by intravesical administration on weeks 1, 2, 5, and 6 of a 12-week cycle, for 4 cycles in one of two cohorts: BCG-unresponsive (Cohort 1); BCG-naïve or BCG-incompletely treated (Cohort 2). Patients in either cohort who exhibit stable disease (SD) or CR at week 12 will continue treatment until week 24; patients with progressive disease (PD) will discontinue treatment. Patients who experience or maintain CR at week 24 will receive additional cycles every 12 weeks until week 48; patients with SD or PD at week 24 will discontinue treatment. Patients with PD at any time after week 24 will discontinue treatment. Phase 2 primary objective: evaluate efficacy (CR rate at week 48) and safety of EG-70. Secondary objectives: evaluate progression-free survival, CR rate at 12, 24, 36 and 48 weeks, and duration of response. The study is being conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and with the principles of the Declaration of Helsinki. All patients provide written informed consent. The ongoing, registration-enabling phase 2 portion of the LEGEND study is anticipated to recruit approximately 100 patients from sites in North America, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .

Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial

IntroductionTotal knee arthroplasty (TKA) is a common surgical intervention to treat joint diseases. However, TKA is associated with significant blood loss. Tranexamic acid (TXA) has been used to reduce perioperative...

Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome — a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

BackgroundDespite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants.Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult.This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE.Methods/designThe ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE.Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years.ResultsThe primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and .”will be stratified for the two treatment groups.DiscussionThe statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.Trial registrationClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Oncology Early-Phase Clinical Trials in the Middle East and North Africa: A Review of the Current Status, Challenges, Opportunities, and Future Directions.

Clinical trials, the empirical discipline of medical experimentation conducted on human subjects, have engendered a paradigm shift in medical research. The need for new clinical studies is paramount in the Middle East and North Africa (MENA) region, with its rising cancer incidence and demand for efficient oncology treatments. This paper comprehensively reviews the challenges, opportunities, and future directions of phase I oncology clinical trials in the MENA region. Early-phase trials are vital in determining drug dosage and assessing toxicity, bridging the gap between preclinical research and clinical practice. Considering the unique landscape of MENA, this review explores regulatory aspects, specific hurdles faced, potential advantages, and areas for improvement in conducting these trials. Various future directions can be pursued to maximize the potential of phase I oncology trials in MENA. While regulatory bodies like the Ministry of Health adhere to the International Conference on Harmonization-Good Clinical Practice guidelines, a unified system meeting high standards would yield better results. Strengthening research infrastructure, establishing research centers, incorporating clinical trial education into the curriculum, and improving access to medical facilities are crucial. Enhancing consumer understanding of research would facilitate increased participation and promote sustainability in trial recruitment. Navigating various funding sources would open the door for more funding opportunities. Collaborations between academia, industry, and regulatory bodies, both international and local, should be fostered to promote knowledge sharing, resource pooling, and harmonization of standards. Such collaborations would contribute to the sustainability of clinical trial activities by leveraging collective expertise, sharing research infrastructure, and distributing the burden of regulatory compliance. By adopting these strategies, the MENA region can advance its capacity to conduct early phases of oncology trials and contribute significantly to the global medical research landscape.

A Review on CDSCO: Central Drug Standard Control Organisation

India has been a hub for managing various multi centre trials the central drug standard control organisation (CDSCO), headed by the drug controller general of India (DCGI), drowsing the regulation for the manage of clinical trials in India the conduct of trails, regulations in India and quality of data generated may be the source for this evolution it is crucial that now all clinical trials conducted in India should as per the international conference of harmonization good clinical practice guidelines ( ICH- GCP) for clinical trials and follow the newly amended schedule Y of the drugs and cosmetic Act.

Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit.

Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit.

Obstructive sleep apnea improves with non-invasive hypoglossal nerve stimulation using temporal interference

BackgroundPeripheral nerve stimulation is used in both clinical and fundamental research for therapy and exploration. At present, non-invasive peripheral nerve stimulation still lacks the penetration depth to reach deep nerve targets and the stimulation focality to offer selectivity. It is therefore rarely employed as the primary selected nerve stimulation method. We have previously demonstrated that a new stimulation technique, temporal interference stimulation, can overcome depth and focality issues.MethodsHere, we implement a novel form of temporal interference, bilateral temporal interference stimulation, for bilateral hypoglossal nerve stimulation in rodents and humans. Pairs of electrodes are placed alongside both hypoglossal nerves to stimulate them synchronously and thus decrease the stimulation amplitude required to activate hypoglossal-nerve-controlled tongue movement.ResultsComparing bilateral temporal interference stimulation with unilateral temporal interference stimulation, we show that it can elicit the same behavioral and electrophysiological responses at a reduced stimulation amplitude. Traditional transcutaneous stimulation evokes no response with equivalent amplitudes of stimulation.ConclusionsDuring first-in-man studies, temporal interference stimulation was found to be well-tolerated, and to clinically reduce apnea-hypopnea events in a subgroup of female patients with obstructive sleep apnea. These results suggest a high clinical potential for the use of temporal interference in the treatment of obstructive sleep apnea and other diseases as a safe, effective, and patient-friendly approach. Trial registrationThe protocol was conducted with the agreement of the International Conference on Harmonisation Good Clinical Practice (ICH GCP), applicable United States Code of Federal Regulations (CFR) and followed the approved BRANY IRB File # 22-02-636-1279.

Atorvastatin and the influence on postoperative atrial fibrillation after surgical aortic valve replacement (STARC) in adults at Odense University Hospital, Denmark: study protocol for a randomised controlled trial

IntroductionAtrial fibrillation (AF) is the most common postoperative complication after surgical aortic valve replacement (SAVR) and occurs in up to 50% of the patients. Development of postoperative AF (POAF) is...

Artificial intelligence-based mining of electronic health record data to accelerate the digital transformation of the national cardiovascular ecosystem: design protocol of the CardioMining study

IntroductionMining of electronic health record (EHRs) data is increasingly being implemented all over the world but mainly focuses on structured data. The capabilities of artificial intelligence (AI) could reverse the...

SUCCESSFUL AYURVEDIC MANAGEMENT OF VICHARCHIKA (ECZEMA) - A CASE STUDY

Vicharchika is skin lesions of varying size with inflammation, severe itching sensation, with bleeding in some cases, and this condition is as distressing as it causes disfigurement by affecting cosmetic look of an individual. In the present case study a 60 years old female consulted in Out-patient Department of Kayachikitsa Rama Ayurvedic Hospital, Rama University Mandhana Kanpur Uttar Pradesh Complain of the patient was recurrent skin rashes with redness, skin edema, intense itching, with crusting of skin flaking, blistering, cracking, oozing and bleeding of upper layer of skin over both hands. By examining the signs and symptoms of complaints of patient was diagnosed with vicharchika. In the present case report patient was intended to treat with some ayurvedic formulations under the treatment of Vicharchika.Vicharchika according to Ayurveda is Rakta Pradoshaja Vikara being involved of three Dosha with dominance of Kapha. The management available in current mainstream medicine is unsatisfactory. Various Ayurvedic treatments have been in use for these manifestations. The patient was considered suffering from Vicharchika and was treated with ayurvedic medicines. Patients condition was assessed for signs and symptoms of eczema which were cured after the treatment. This study is carried out as per International conference of Harmonization-Good Clinical Practices Guidelines (ICH-GCP) as per Declaration of Helsinki guidelines. This study shows that the cases of eczema can be successfully managed with Ayurvedic treatment only without any complications and side effects.

Second-generation antipsychotics and seizures – a systematic review and meta-analysis of serious adverse events in randomized controlled trials

Seizures are suspected to be side effects of antipsychotics. To examine a possible causal relationship, we compared the risk of seizures on second-generation antipsychotics to the risk on placebo in randomized controlled clinical trials (RCTs) across diagnostic groups. The primary outcome was any seizure reported as International Conference on Harmonisation-Good Clinical Practice (ICH-GCP)-defined serious adverse event (SAEs). The risk ratio (RR) with antipsychotics versus placebo was synthesized in a pairwise common effects Mantel-Haenszel meta-analysis. For 314 of 597 idenitified placebo-controlled RCTs information about all SAEs could be retrieved from publications, original investigators, pharmaceutical companies and the European Medical Agency. In those, 37 seizures occurred in 42,600 participants on antipsychotics (0.09%) and 28 in 25,042 participants on placebo (0.11%). The meta-analytic results (RR 0,68; 95% Confidence Interval 0.41-1.12) indicated a reduced risk on antipsychotics with a confidence interval including no difference (i.e. RR=1). Neither in sensitivity analyses (excluding events in the safety-follow-up of trials or first-generation antipsychotics; using odds ratios) nor in subgroup analyses (on specific antipsychotics, drug combinations, diagnostic categories, age groups, and study duration) there was evidence for an increased risk on antipsychotics, except for some weak indications of an increased risk on antipsychotics in older and/or demented participants (RRs 1.11 and 1.48, respectively, but with 95% CIs of 0.35-3.49 and 0.41-5.26 including no difference and subgroup tests with p=0.54 and p=0.66 not indicating differences between age groups or diagnostic categories). Consequently, there are no indications that second-generation antipsychotics cause seizures in middle-aged adults and children in most diagnostic groups; rather our results provide some weak evidence for a protective effect. However, there was no data on SAEs available for clozapine, for which observational studies provide the strongest associations with increased seizure rates, and for older and/or demented patients a small additional risk on antipsychotics cannot be excluded.

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry)

IntroductionClozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited...

Randomized Trials Fit for the 21st Century: A Joint Opinion From the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation.

Randomized Trials Fit for the 21st Century: A Joint Opinion From the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation.

Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study

IntroductionSmall molecule inhibitors of the terminal step in intrahepatic triglyceride synthesis (diacylglycerol acyltransferase 2 inhibitor (DGAT2i, PF-06865571, ervogastat)) and upstream blockade of de novo lipogenesis via acetyl-coenzyme A carboxylase inhibitor...

Fraud and Deceit in Medical Research

Fraud and Deceit in Medical Research

Risk of Unmasking on Schizophrenia Double Blind Clinical Trials Using Risperidone versus Comparator As A Result of Laboratory Analysis

Background: Randomized double blind clinical trial is the most used and accepted method of clinical research involving human subjects. Clinical researches are performed under strict regulatory regulations including Helsinki Declaration and International Conference for Harmonization Good Clinical Practice (ICH – GCP) recommendations. As per ICH GCP principles safety and well being of clinical trials patients should prevail over research objectives and their health status should be monitored throughout the trial using objective and concise indicators such as but not limited to laboratory analysis. This study aims to identify factors that might unblind risperidone treatment arms for patients enrolled in randomized double blind schizophrenia clinical trials using risperidone versus comparator, as a result of reviewing safety laboratory analysis. Methods: This study included 134 controlled schizophrenia patients who received treatment with risperidone versus antipsychotic agents with lower dopamine antagonist potency. Prolactine values were determined using imunoenzimatic and colorimetric method (ELISA) for cantitative determination of prolactine from serum or plasma. Results: 84% percent of the patients treated with risperidone showed elevated levels for prolactine above laboratory reference ranges defined as: Men ( 1.8 – 17.0 ng/ml) ; Women ( fertile 1.2 – 19.5 ng/ml, menopause 1.5 – 18.5 ng/ml) Conclusions: High elevated values of prolactin were determined for risperidone treated patients which might disclose the patient treatment arm to blinded investigator and jeopardize the research. As lab results are an essential safety factor of clinical trial those cannot be overruled and establishing Independent Data Monitoring Committee to oversee patients’ data and warn the investigator is recommended.

Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies.

Background:Achondroplasia is the most common short-limbed skeletal dysplasia resulting from gain-of-function pathogenic variants in fibroblast growth factor receptor 3 (FGFR3) gene, a negative regulator of endochondral bone formation. Most treatment options are symptomatic, targeting medical complications. Infigratinib is an orally bioavailable, FGFR1–3 selective tyrosine kinase inhibitor being investigated as a direct therapeutic strategy to counteract FGFR3 overactivity in achondroplasia.Objectives:The main objective of PROPEL is to collect baseline data of children with achondroplasia being considered for future enrollment in interventional studies sponsored by QED Therapeutics. The objectives of PROPEL 2 are to obtain preliminary evidence of safety and efficacy of oral infigratinib in children with achondroplasia, to identify the infigratinib dose to be explored in future studies, and to characterize the pharmacokinetic (PK) profile of infigratinib and major metabolites.Design:PROPEL (NCT04035811) is a prospective, noninterventional clinical study designed to characterize the natural history and collect baseline data of children with achondroplasia over 6−24 months. PROPEL 2 (NCT04265651), a prospective, phase II, open-label study of infigratinib in children with achondroplasia, consists of a dose-escalation, dose-finding, and dose-expansion phase to confirm the selected dose, and a PK substudy.Methods and analysis:Children aged 3−11 years with achondroplasia who completed ⩾6 months in PROPEL are eligible for PROPEL 2. Primary endpoints include treatment-emergent adverse events and change from baseline in annualized height velocity. Four cohorts at ascending dose levels are planned for dose escalation. The selected dose will be confirmed in the dose-expansion phase.Ethics:PROPEL and PROPEL 2 are being conducted in accordance with the International Conference on Harmonization Good Clinical Practice guidelines, principles of the Declaration of Helsinki, and relevant human clinical research and data privacy regulations. Protocols have been approved by local health authorities, ethics committees, and institutions as applicable. Parents/legally authorized representatives are required to provide signed informed consent; signed informed assent by the child is also required, where applicable.Discussion:PROPEL and PROPEL 2 will provide preliminary evidence of the safety and efficacy of infigratinib as precision treatment of children with achondroplasia and will inform the design of future studies of FGFR-targeted agents in achondroplasia.Registration:ClinicalTrials.gov: NCT04035811; NCT04265651.

293 Distinct tumor infiltrating treg lineages are associated with response to anti-PD1 checkpoint blockade in non-small cell lung cancer

BackgroundImmune-checkpoint blockade (ICB) has proved a major success, especially in highly mutated tumors such as lung cancer. Nevertheless, not all patients respond to ICB.1 It is possible that regulatory T cells (Tregs) play a role in this lack of response by suppressing tumor-reactive cytotoxic T cells,2 however the specific mechanisms that lead to this suppression remain elusive. Additionally, Tregs are necessary for protection against autoimmune disease3 and broadly depleting them could induce severe immune adverse events. It is therefore necessary to understand the functional programming and suppressive nature of Treg subsets in the tumor microenvironment to define targetable molecules for future biomarker-driven therapeutics.MethodsIn this study we performed single cell RNA-sequencing on T cells isolated from resected tissue and peripheral blood from 15 neoadjuvant nivolumab (anti-PD1)-treated and 10 untreated non-small cell lung cancer (NSCLC) patients. We identified and analyzed 71,251 CD4+ FoxP3+ Tregs. Refined clustering was performed, and we used pseudotime and differential gene analyses to understand the transcriptional relationship between clusters and patient groups. We plan to relate our Treg subcluster compositions and enriched gene sets with previously defined mouse models of ICB response as well as human head and neck squamous cell carcinoma (HNSCC).ResultsWith our highly refined clustering approach, we identified 7 distinct Treg clusters that could reflect differing functionalities within the tumor microenvironment. We demonstrate two separate Treg subsets that diverge towards either an activated state, expressing members of the tumor necrosis factor receptor (TNFR) superfamily: OX40, 41BB, GITR, or a resting state. These lineages separate ICB responders from non-responders, whose tumors are enriched in activated Tregs. We plan to stimulate receptors associated with non-response using agonist ligands or antibodies and hypothesize that their induced signaling will result in transcriptional program changes leading to highly suppressive Tregs.ConclusionsTogether, this study provides an in-depth look at the Treg-derived suppressive mechanisms governing their function in the TME of anti-PD-1-treated vs. untreated tumors. Using biospecimens obtained from the neoadjuvant setting, we were also able to study the impact of PD-1 blockade on Treg intra-tumoral function. This in-depth analysis of tumor Tregs has identified specific targetable biomarkers which could be used to improve ICB response while mitigating off-target immune adverse events by specifically inhibiting a small subset of Tregs without disturbing systemic immune homeostasis.ReferencesForde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. Neoadjuvant PD-1 blockade in resectable lung cancer. N Engl J Med [Internet] 2018 April 16;378(21):1976–86. Available from: https://doi.org/10.1056/NEJMoa1716078Bonertz A, Weitz J, Pietsch DK, Rahbari NN, Schlude C, Ge Y, et al. Antigen-specific tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J Clin Investig 2009;119(11).Montane J, Bischoff L, Soukhatcheva G, Dai DL, Hardenberg G, Levings MK, et al. Prevention of murine autoimmune diabetes by CCL22-mediated treg recruitment to the pancreatic islets. J Clin Invest [Internet] 2011/07/01. 2011 August 1;121(8):3024–8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21737880Ethics ApprovalThis study was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center (NA_00092076; NCT02259621) and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The patients described in this study provided written informed consent.

CLINICAL EVALUATION OF THE ROLE OF SARIVA PHANTA (HEMIDESMUS INDICUS R. BR.) IN THE TREATMENT OF MADHUMEHA (DIABETES MELLITUS OR TYPE II DIABETES) WITH SPECIAL REFERENCE TO ITS HYPOGLYCAEMIC EFFECT

Diabetes is a complex endocrine disease that affects more than 100 million of people worldwide (6% of the total population). The prevalence of Diabetes mellitus is increasing, despite multiple treatment options. Along with allopathic medications, several formulations or single forms of plant origin are employed in its treatment, especially in non-insulin dependent diabetic mellitus (NIDDM). Herbal medications are effective, broad range of action, fewer adverse effects, and are relatively inexpensive, making them a suitable alternative. The aim of this study is to investigate hypoglycaemic effect of Sariva (Hemidesmus indicus R.Br.) root phanta (teabag) in Madhumehi. The current trial is a randomised, parallel group interventional trial. After initial screening for inclusion criteria, 60 patients were enrolled and separated into 3 groups (20 patients each), which was conducted according to the International Conference on Harmonization-Good Clinical Practices Principles (ICH-GCP) or the Declaration of Helsinki guidelines and statistically analysed using the chi square test. Madhumeha had a better clinical outcome with the medication. The majority of vata-kaphaja prakriti had side effects such as constipation and nausea. Patients in the 40–50-year age group with Vataja-dosha derangement were found to be more prone to DM-2. In married mostly in males, there is a greater preponderance. Madhura, snigdha guṇa relieves vata, Tikta rasa relieves kapha, meda duṣya, sheeta virya relieves pitta; Hence it has tridoṣatmaka activity, which is beneficial in the treatment of Madhumeha. Sariva in the form of teabag has kaphaghna, vataghna, kandhughna (curing pruritus), meha durgandhi nashan, sarvamehahara properties. Thus, it collectively acts in Madhumeha.

An Open, Non-Randomised, 1/2 Phase Study on the Safety, Tolerability, and Immunogenicity of Single Dose 'Sputnik Light' Vaccine for Prevention of Coronavirus Infection in Healthy Adults

Background: While the world is experiencing another wave of COVID-19 pandemic, global vaccination program is hampered by obvious shortage in supply of licensed vaccines. Development of new vaccines that are easy to manufacture and administer is highly desirable to overcome hurdles in vaccine scaling up and distribution, especially in developing countries. In the effort to satisfy vaccine demands we developed a new single dose vaccine based on recombinant adenovirus type 26 (rAd26) vector carrying the gene for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein – “Sputnik Light”.Methods: We conducted an open label, two-stage, prospective, non-randomized phase I-II trial aimed to assess safety, tolerability and immunogenicity of “Sputnik Light” vaccine in a single center in Russia. Primary outcome measures were antigen-specific humoral immunity (Anti-RBD-SARS-Cov2 antibodies measured by ELISA on days 1, 10, 28, and 42) and safety (number of participants with adverse events monitored throughout the study). Secondary outcome measures were antigen-specific cellular immunity (measured by antigen-dependent CD4+ and CD8+ T-cell proliferation, number of antigen-specific interferon-γ-producing cells as well as interferon-γ concentration upon antigen restimulation) and change in neutralizing antibodies (measured in SARS-CoV-2 neutralization assay). The trial is registered at ClinicalTrials.gov (NCT04713488).Findings: Between January 14 and 27, 2021, 150 participants were screened, of whom 110 were enrolled. Most of solicited adverse reactions were mild (66.4% from all vaccinees), few were moderate (5.5%). No serious adverse events were detected. Assessment of Anti-RBD-SARS-Cov2 antibodies revealed group with pre-existing immunity to SARS-CoV-2. Upon this finding we separated all safety and immunogenicity data according to pre-existing immunity to SARS-Cov2. There were notable differences in the vaccine effects on immunogenicity by the groups. Vaccination of seropositive (N=14) volunteers rapidly boosted RBD-specific IgGs from reciprocal geometric mean titer (​GMT) 594.4 at a baseline up to 26899 comparing to 29.09 in seronegative group (N=96) by day 10. By day 42 seroconversion rate reached 100% (93/93) in seronegative group with GMT 1648. At the same time in seropositive group seroconversion rate by day 42 was 92.9% (13/14) with GMT 19986. Analysis of neutralizing antibodies to SARS-CoV-2 showed 81.7% (76/93) and 92.9% (13/14) seroconversion rates by day 42 with median reciprocal GMT 15.18 and 579.7 in the seronegative and seropositive groups, respectively. Each test to assess cell-mediated immune reactions was carried out on a separate group of 30 volunteers on day 10 upon vaccination. Antigen-specific T cell proliferation, formation of IFNy-producing cells, as well as IFNy secretion were detected in 96.7% (26/27), 96% (24/25) and 96% (24/25) seronegative and in 100% (3/3) 100% (5/5) and 100% (5/5) seropositive vaccinees, correspondingly.Interpretation: The single dose rAd26 vector-based COVID-19 vaccine “Sputnik Light” has a good safety profile and induced strong humoral and cellular immune responses both in seronegative and seropositive participants. Further investigation is needed to assess the effectiveness of this vaccine against COVID-19 used for primary and secondary vaccination.Clinical Trial Registration Details: The trial is registered at ClinicalTrials.gov (NCT04713488).Funding Information: Russian Direct Investment Fund.Declaration of Interests: OVZ, TAO, IVD, OP, DVS, DMG, ASD, AIT, DNS, IBE, EAT, AGB, ASE, FMI, NAN, NLL, ASS, SVB, BSN, DYL, ALG report patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19. All other authors declare no competing interests.Ethics Approval Statement: The trial was approved by the local ethic committee and was conducted with the approval of the Ministry of Health of Russian Federation in compliance with International Conference on Harmonization and National Good Clinical Practice guidelines and Declaration of Helsinki.