Drug Controller General Of India Research Articles

Amidst Cytokine Storm in Metabolic Diseases: Can 2-deoxy-D-glucose (2-DG) Cure COVID-19?

Abstract: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pandemic disease COVID-19, which began in China in 2019, became the leading cause of fatalities globally. The transmission rate of the virus is directly proportional to the so-called ‘dance dynamic’ energy of the spike protein as this phenomenon favours the ligand-receptor binding. The clinical spectrum of the COVID-19 disease, which includes (inflammation, cytokine storm, and multi-organ dysfunction), puts Corona Warriors active in various aspects of the disease, such as the efficient management of critically ill COVID-19 patients, in danger of losing their lives. Due to its effects on an ancient oxygen-independent glycolytic pathway, anti-inflammatory properties, and competitive interaction with viral proteins, 2-deoxy-D-glucose (2-DG), which is being developed in India at the Defence Research and Development Organization (DRDO), has emerged as a ground-breaking agent for COVID-19 treatment. After a virus gains entry into host cells, it is found that metabolic reprogramming takes place to meet the nutritional and energy requirements for virus reproduction. The recent approval of 2-DG for adjunctive emergency usage by the Drug Controller General of India (DCGI) may mark a turning point in the management of mild to moderate COVID-19 infection.

Cervical Cancer and Human Papilloma Virus (HPV) Vaccines: A primer for General Physicians

India contributes close to 20% of the global cervical cancer burden. This article reviews the preventive strategies against cervical cancer and suggest a few way forward for the prevention of cervical cancer in India. A literature review of online databases (Embase, Google Scholar, PubMed, Scopus) and reports from government websites regarding cervical cancer and HPV vaccination in India was conducted. Currently, four different HPV vaccines are available in India: a bivalent vaccine, a nonavalent vaccine and two quadrivalent vaccines. To reduce India’s cervical cancer burden, the National Technical Advisory Group on Immunization (NTAGI) has advocated the widespread implementation of HPV vaccination. An indigenous HPV vaccine was given market authorisation by the Drugs Controller General of India (DCGI) in July 2022. There is a need to raise awareness regarding the benefits of HPV vaccines in India. The introduction of indigenous HPV vaccine might enhance the supply logistics and may increase the uptake of the vaccine.

Bilastine in Refractory Chronic Spontaneous Urticaria: Disease Control and Cytokine Modulation in an Open-label Prospective Study

Introduction: The treatment options for chronic spontaneous urticaria (CSU) primarily include second generation non-sedative antihistamine (SGAHs). Bilastine is a newer, nonsedating SGAH approved for urticaria in February 2019 by the Drugs Controller General of India. Its major advantages are in terms of superior efficacy, lack of drug interactions and adverse effects, including sedation, compared to conventional SGAHs. The role of cytokines in the pathogenesis of CSU is well known. However, there is a shortage of data regarding the change in serum levels of proinflammatory cytokines following H1 antihistamines. We conducted this trial to evaluate the role of bilastine in cytokine modulation and autoimmunity, thereby explaining its role in modifying the disease process in CSU. Materials and Methods: This prospective study was conducted in a tertiary institute in Kolkata on patients aged 12 years and above with a CSU >6 months. These patients had an unsatisfactory response, as per the Urticaria Activity Score 7 (UAS7), to previous antihistamine therapies in standard doses. Treatment effectiveness was determined by comparing the UAS7 at baseline with that at weeks 4, 8 and 12. Also, baseline serum interleukin-6 (IL-6) and IL-17 were compared with those at the end of the study, that is, 12 weeks. Results: Thirty patients who matched the inclusion criteria and signed informed consent were included in the study. At the end of 12 weeks, 10% of patients (n = 3) achieved a complete treatment response (UAS = 0), whereas 43.33% of patients (n = 13) were labelled as having well-controlled urticaria (UAS <6). At 12 weeks, the mean UAS7 score (6.47 ± 4.45) was statistically significant compared to the baseline score (25.47 ± 7.74). The mean values of serum IL-6 (pg/ml) and IL-17 (pg/ml) at baseline were 5.96 ± 5.24 pg/ml and 6.96 ± 5.97 pg/ml, respectively. At the end of treatment, that is, 3 months, the mean values were reduced to 4.61 ± 4.56 pg/ml and 5.08 ± 3.87 pg/ml. The reduction was statistically significant for both serum IL-6 (P < 0.001) and IL-17 (P < 0.0001). Conclusion: We conclude that bilastine at a once-daily continuous dose of 40 mg for 3 months is safe and effective in CSU patients who are refractory to treatment at the standard doses of SGAHs. Improved symptomatic control with bilastine was also associated with better control over the inflammatory process, as suggested by the lowering of mean cytokine levels in our study.

Academic Clinical Trials Submitted to an Institutional Ethics Committee at a Tertiary Care Center: A Retrospective Analysis.

Background The role of academia in clinical research has given rise to the concept of academic clinical trials (ACTs), which are vital in generating evidence. Through the implementation of the New Drugs and Clinical Trials Rules-2019 (NDCTR-2019) rules, the Institutional Ethics Committee (IEC) has obtained a quasi-regulatory role. The study aims to assess the challenges the IEC faced when processing, approving, and monitoring ACTs. The other objectives included the number of ACTs submitted to the IEC, as well as administrative, scientific, and ethical issues stated by the IEC and the Drug Controller General of India (DCGI) authorities. We also aimed to provide some insight into the type of decision made by IEC and DCGI - the delay or inconsistency between the queries. Methods This retrospective study was conducted in the IEC of a tertiary care hospital, Mumbai, Maharashtra, India. A comprehensive search of the IEC database was carried out by the study team, and only those protocols of ACTs submitted to IEC between January 2015 and December 2021 were included. The studies submitted between January 2015 and February 2019, i.e., before the release of NDCTR-2019, were classified as the "Before" category. All subsequently submitted protocols were grouped together as the "After" group. Descriptive statistics were used to represent the data, while comparison between the two timeframes were made using the Mann-Whitney U test with a level of significance at 5%. Results This six-year study showed that merely 1.4% (34/2400) trials fulfilled the criteria of an ACT. An increase in the ACT protocol submission was noted in the "After" group (20 vs. 14). Most ACTs were drug trials, with 67.6% (23/34) trials conducted majorly in the Department of Anesthesiology. There was a statistical increase in time query reply by the principal investigator to IEC and the time between submission and approval in the "After" group (p<0.05). IEC sent out 94 administrative, 565 scientific, and 216 ethical queries. On IEC monitoring, protocol deviations were noted; nonetheless, no ACTs reported protocol deviations or serious adverse events. Conclusions Since the implementation of NDCTR-2019, IEC has taken on a quasi-regulatory function, and there has been an increase in the caliber of IEC monitoring and adherence to ethical norms.

Emergency Approval Mechanisms for Human Vaccines in India.

The coronavirus disease 2019 (COVID-19) pandemic highlighted the world's level of preparedness in managing public health emergencies (PHEs). It revealed the critical need for timely medical therapeutics, especially vaccines. To expedite response, many nations, including India, adopted emergency approval mechanisms and offered new ways of review, such as the rolling review along with the accelerated review procedure. This response resulted in reallocating internal resources and adopting new policies and measures, such as integrating digital technology with regulatory submissions and flexibility in statistical approaches. The present review focuses on the utilization of the New Drugs and Clinical Trials Rules 2019 for granting emergency approval to COVID-19 vaccines by the Drug Controller General of India (DCGI) and explores the legislative basis for such authorization during the PHE. The review aims to elucidate key intricacies and challenges inherent in the existing 'emergency use' framework within the Indian regulatory landscape. It assesses three critical facets of the 'emergency use' paradigm: the definition of the term, establishment of a transparent decision-making process, and formulation of rules governing termination or expiration of the emergency status. It makes policy recommendations regarding the 'emergency use' framework to respond to new, emerging, or re-emerging public health threats of the future.

Evaluation of knowledge and awareness of clinical trials among undergraduate, interns, and postgraduate medical students

Background: Clinical trials aim to improve health care by reducing treatment costs, enhancing quality, and advancing the discovery of safe treatments. Notably, limited knowledge among resident doctors may impact research quality. Aims and Objectives: The study seeks to evaluate awareness and knowledge of clinical trials among undergraduate, intern, and postgraduate medical students. Materials and Methods: It was an observational, cross-sectional study conducted on 300 medical students over 3 months after approval from the Institutional Ethics Committee (IEC). The pre-validated questionnaire containing 24 items was administered through email, WhatsApp, or in person. Data were analyzed using descriptive statistics. Results: In the study, 96.7% of participants believe the necessity of clinical trials. Notably, 72% of undergraduates and 76% of postgraduates express willingness to participate in a clinical trial. Furthermore, 93% of participants view trials as vital for innovative therapies, and 74.3% believe that they enhance health-care services. Knowledge gaps in clinical trials were evident: 56.3% of participants knew good clinical practice guidelines, 46.7% of participants were aware of them, and only 12.3% of participants knew the IEC role. However, 66.7% of participants recognized the Drug Controller General of India (DCGI) and IEC approvals as crucial for trials, and 53.7% of participants identified DCGI as the regulatory authority. 68.3% of participants could not define a placebo-controlled trial. However, 75% of participants were aware of the consequences of informed consent form non-compliance. Most knew about post-marketing surveillance (80.33%), but awareness of healthy volunteer involvement in Phase 1 was lower (48%). In addition, 62.33% of participants knew about marketing access after Phase 3, and 60% of participants were aware of adverse effects reporting procedures. Conclusion: The study reveals a concerning lack of awareness regarding clinical trials among undergraduate, intern, and postgraduate medical students, emphasizing the need for targeted educational interventions in medical curricula.

A Review on Banned Drugs

India has become a hub for the availability and usage of banned or harmful medicines such as Nimesulide, D’cold, Novalgin, Lomofen, and Rofecoxib, among others. The decision to ban a drug is based on the risk versus benefit ratio evaluated through post-marketing surveillance and the Adverse Drug Reaction Reporting System. Pharmaceutical negligence among doctors can lead to hazardous effects on the general health of a patient. It is important for the government to spread information on drugsideeffects. The prescribing of drugs is an essential practice for medical professionals. In promoting a healthy lifestyle, the prevention of diseases is important, but equally important is treatment of such diseases with safe drugs. Every drug has some side effects, but with the correct dosage, it can be avoided. Banned drugs have more adverse/side effects. Drugs that are found unsafe in post-marketing surveillance are banned by regulatory authorities. The Drug Controller General of India (DCGI) is the highest authority in India to approve or ban a drug. Despite this, banned drugs are still available in developing countries such as India due to a lack of law enforcement, physician awareness, and drug control authorities failing to inform hospitals of the status of medicine. India is a major hub for banned drugs.

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.

Update on Treatment of Covid-19 in Children

Since its emergence in December 2019 in Wuhan, China, more than three years, and a half has passed, yet the world is still grappling with the far-reaching impacts of the COVID-19 pandemic. Many countries endured a devastating blow during the second wave of COVID-19, witnessing a significant rise in severe cases among children and instances of multisystem inflammatory syndrome in children, surpassing the numbers seen during the initial wave of the pandemic [1]. While numerous countries have successfully developed effective COVID-19 vaccines for adults, options for pediatric populations have only recently emerged. The Drugs Controller General of India (DCGI) granted emergency approval for the use of COVISHIELD and COVAXIN in pediatric patients aged 12 years and older [2]. However, despite considerable research efforts, a definitive cure or treatment for COVID-19 remains elusive. Several drugs, including remdesivir, casirivimab/imdesivimab, ivermectin, baricitinib, and tofacitinib, have garnered significant attention, but none can be hailed as a panacea [3].

Meridine and Xestosaprol M have Potential Anti-Virus Resembling Remdesivir

The rise and fall of the COVID-19 wave continue to be watched because the right antiviral drug has not yet been found. Remdesivir is an antiviral drug that is much sought after, especially when the number of COVID-19 cases is spreading worldwide. Until now, the US Food and Drug Administration (FDA) and the Drugs Controller General of India (DCGI) have confirmed the treatment for COVID-19 infection is remdesivir; because of that, remdesivir is very expensive and difficult to find, so that other similar or alternative drugs are needed. Even better ones with better potential too. Based on studies, insilico meridine and xestosaprol M have the same potential as remdesivir as an anti-COVID-19 virus.

Levodropropizine: A promising peripherally acting antitussive agent

Cough is one of the most frequent symptom for patients to seek medical attention. Cough can be associated with many disease processes and the ultimate treatment depends on determining the etiology and diagnosis. Antitussive agents with different mechanisms of action have been developed in the past, but there are still very few medications that seem to be effective without any side effects especially related to central nervous system (CNS). Levodropropizine is an antitussive agent which acts peripherally and is a non-opioid cough medication that is in use since many years as a symptomatic therapy for cough. Levodropropizine has potent antitussive activity mainly due to peripheral effects by inhibiting the activation of vagal C-fibers. In fact, levodropropizine has been proven effective in controlling cough and is devoid of the central depressant effect. Levodropropizine oral suspension (30mg/5ml) is approved by drug approval body of India, Drug Controller General of India (DCGI) for the management non-productive cough in adults. Levodropropizine is approved in some of the European countries and in Asian countries. It is widely used in Republic of Korea for the symptomatic treatment of cough in both adults and children above 2 years of age. Levodropropizine has the utmost level of benefit in comparison with central antitussive agents namely codeine and dextromethorphan for the patients with cough due to acute and chronic bronchitis.

Knowledge and perception of health-care professionals on clinical trials in India: A pan-Indian cross-sectional survey.

The purpose of the study was to evaluate the knowledge and perception of health-care professionals (HCPs), such as doctors/surgeons, pharmacists, nurses, optometrists, and lab technicians, on clinical trials (CTs) in India. The study was a pan-Indian cross-sectional survey initiated by the Indian Ophthalmology Clinical Trial Network (IOCTN) by using a previously validated questionnaire for three months of data collection. An online survey was used to record information regarding demographics, CT knowledge, and CT perception among HCPs. A total of 630 responses were recorded from HCPs: 207 doctors and surgeons, 159 pharmacists, and 264 laboratory technicians, nurses, and optometrists across India. Over 90% of HCPs had a clear knowledge on the purpose of CTs, the informed consent (IC) process, ethical approval by the Drugs Controller General of India (DCGI). About 80% and 90% were aware of confidentiality of patients, voluntariness of participation, and good clinical practice. Surprisingly, less than 50% had lesser knowledge regarding monetary incentives of CT participants (CTPs). A slightly positive perception was observed regarding the potential benefits of CTPs, compensation related to injury, and importance of obtaining IC. Less than 50% had a negative perception that monetary compensation to CTPs led to bias and deprivation of standard treatments. However, no significant difference was observed between other aspects of demographics and perception regarding CTs. We observed doctors and surgeons to be having the highest regarding CTs, followed by pharmacists. The survey highlighted the necessity of scheduling awareness programs among the HCPs, which would improve their misconceptions and perception of CTs while interacting with patients for CT enrollment.

Effect of circulating tumor cells distribution in treatment naive and treated patients with advance stage breast cancer on disease burden.

e12517 Background: Breast malignancies is a leading cause of cancer-related mortalities and show ascending incidence rate. Despite advancements in our understanding of the disease, its clinical outcome is often dismal. This largely remains owing to the characteristic wide window of relapse, spanning months to decades after primary treatment. Therefore, continuous monitoring of the disease is an offered choice to detect metastatic progression and recurrence. Circulating tumor cells (CTCs) have emerged as a powerful prognostic tool to predict the disease outcome in many epithelial cancers. CTCs are a real-time surrogate biomarker accounting for minimal residual disease (MRD) which is often missed in CT PET scanning. This leads to a progression of metastasis when the patient is often considered as ‘clinically disease free’. Here, we analyzed the presence of CTCs in treatment-naïve and chemo-recipient breast cancer patients. Methods: In this retrospective study on 417 breast cancer patients, CTCs were isolated from 1.5 ml of blood using the Drug Controller General of India (DCGI) approved OncoDiscover CTC test. This platform contains affinity-based magnetic nanoparticles to mediate EpCAM-based CTC isolation. CTCs were detected as CK18+, DAPI+ and CD45- cells based on automated digital imaging platform. Results: 42.6 % (n=178) of patients were clinically at progressive stage (stage II and III) and treatment naïve. On the other hand, 47.4 % of patients received treatment including surgery and chemotherapy. CTCs were not observed in 5.6 % (n=10) of the treatment naïve population while 32% (n=75) of patients who received therapy did not show CTCs. The mean CTC number in treatment naïve patients was 15, while the mean CTC count in patients receiving therapy was drastically reduced to 2. This implied that therapy effectively countered the tumor progression and reduced the shedding of tumor cells in circulation. The distribution of CTC in treatment naïve patients exhibited a bimodal trend centered at values of 10 and 50, suggesting two distinct populations of patients with respect to CTC count. CTC count did not show any correlation with the age in both population groups. Surprisingly CTC count in younger patients (20-50 years) was 50% higher compared to the older population (50-75 years). Conclusions: The presence of CTCs in treatment naïve, progressive breast cancer patients indicated the biologically aggravated disease. Although therapeutic intervention drastically reduced the CTC burden, their presence in a large population was suggestive of an MRD and the likelihood of recurrence after discontinuation of therapy. A distinct pattern of CTC occurrences in Tx naïve and Tx recipient patient suggested that CTCs can be an important clinical indicator to monitor the therapy response, progression and residual disease.

704/DNA vaccines leverage cytoplasmic DNA stimulation to promote anti-HIV neutralizing antibody production in mice and strong immune response against alpha-fetoprotein in non-human primates

Genetic immunization is an attractive approach for prophylactic and therapeutic vaccination using synthetic vectors to deliver antigen-encoding nucleic acids. Recently, DNA delivered by a physical means or RNA by liposomes consisting of four different lipids demonstrated good protection in human phase III clinical trials and received Drugs Controller General of India and US FDA approval to protect against COVID-19, respectively. However, the development of a system allowing for efficient and simple delivery of nucleic acids while improving immune response priming has the potential to unleash the full therapeutic potential of genetic immunization. DNA-based gene therapies and vaccines have the potential for rapid development, as exemplified by the recent approval of Collategene, a gene therapy to treat human critical limb ischemia, and ZyCoV, a DNA vaccine delivered by spring-powered jet injector to protect against SARS-CoV2 infection. Recently, we reported amphiphilic block copolymer 704 as a promising synthetic vector for DNA vaccination in various models of human diseases. This vector allows dose sparing of antigen-encoding plasmid DNA. Here, we report the capacity of 704-mediated HIV and anti-hepatocellular carcinoma DNA vaccines to induce the production of specific antibodies against gp120 HIV envelope proteins in mice and against alpha-fetoprotein antigen in non-human primates, respectively. An investigation of the underlying mechanisms showed that 704-mediated vaccination did trigger a strong immune response by (1) allowing a direct DNA delivery into the cytosol, (2) promoting an intracytoplasmic DNA sensing leading to both interferon and NF-κB cascade stimulation, and (3) inducing antigen expression by muscle cells and presentation by antigen-presenting cells, leading to the induction of a robust adaptive response. Overall, our findings suggest that the 704-mediated DNA vaccination platform is an attractive method to develop both prophylactic and therapeutic vaccines.

Naftifine: A Topical Allylamine for Superficial Dermatophytosis.

Dermatophytosis is a very common public health problem with high prevalence. Dermatophytes are a highly specialized set of filamentous fungi, which are adapted to keratinized tissues of humans and animals. Dermatophytosis is the most common fungal infection worldwide, affecting approximately 20-25% of the world's population. The etiological agents of dermatophytosis, called dermatophytes, change with geography and socioeconomic status. Trichophyton rubrum (T. rubrum) is the prime species for skin and nail infections followed by T. mentagrophytes/ T. interdigital complex. There is a shift from T. rubrum to T. mentagrophytes in India for superficial fungal infections. In order to deal with fungal infections, treatment strategies involve the use of systemic antifungals and/or topical antifungal agents. Naftifine is a synthetic allylamine antifungal first reported in 1974 and in 1985 became the first commercially available allylamine. The highly lipophilic nature of allylamine allows efficient penetration and reasonably high concentrations in the stratum corneum (SC) and hair follicles. Naftifine is fungicidal as well as fungistatic. The higher efficacy rates of allylamines over imidazoles for the treatment of fungal infections, even for months after cessation of treatment, is thought to be due to their fungicidal effect, as well as to potentially greater keratin binding and slower release from the SC. The effectiveness of naftifine is also demonstrated against various bacteria belonging to both gram-negative and gram-positive classes. The antiinflammatory property of naftifine has been reported in various preclinical studies where it has been shown to target the prostaglandin pathway. Naftifine 1 and 2% gel and cream is approved by The United States Food and Drug Administration (USFDA), recently naftifine has been approved in India by the Indian regulatory authority Drug Controller General of India (DCGI) for the treatment of dermatophytosis. Naftifine 2% also appears to be a promising treatment, requiring fewer applications than the 1% formulation. Naftifine appears to be effective in a single dose and has a shorter treatment duration than azoles. Naftifine demonstrated its efficacy and safety in various clinical studies of tinea infections. Naftifine offers a very useful and promising option for treating dermatophytosis.

Detection of neutralizing antibody towards spike protein of SARS-Cov-2 in vaccinated subjects

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in December 2019 in Wuhan, China causing a severe acute respiratory disease (COVID-19). The virus has rapidly spread into a pandemic affecting over more than 40 million &amp; mortality more than 5 million as per recent data.Due to lack of specific treatment vaccination was considered as main measures to control the pandemic. India’s drugs regulator, Drugs Controller General of India (DCGI) authorized emergency use for AZD1222/Covishield (ChAdOx1-Recombinant) and BBV152/Covaxin in January 2021 and vaccination was started beginning with healthcare and frontline workers and to all aged above 18 years. The present study aimed to know the presence of neutralizing antibodies in vaccinated subjects with or without history of infection by SARSCov-2. Materials &amp; Methods: After obtaining Institutional Ethical Clearance 260 Vaccinated subjects who consented to participate were included for the study. Details were recorded in the proforma. After sterile precaution about 2 ml blood sample was collected in plain vacutainer tube &amp; Serum sample was separated and stored at -20 0C. The neutralizing antibody towards spike protein was detected by performing commercial ELISA (MICROLISA, J MITRA) according to the manufacturer’s guidelines. The results were interpreted by calculating Inhibition rate which is above 30% was considered as positive. Result: Among 260 vaccinated subjects 197(75.6%) positive for neutralizing antibody. Among them 178(76.2%) were Covishield and 82(74.07%) Covaxin vaccinees. Age &amp; sex distribution were recorded the highest in 18-40 years 35 106(53.8%) &amp; female 61(54.4%). Vaccinated and infected 151(86.2%) &amp; only vaccinated 46(54.1%). Good antibody titre was observed in 78.5% upto 4 months of vaccination. Conclusion: The vaccinated subjects with history of SARS-cov-2 infection showed better neutralizing antibody titre with good percentage of persistence Nab till 4th months of post vaccination period.

A SYSTEMIC REVIEW COVID-19 VACCINE

One of the biggest issues facing the world now is the COVID-19 epidemic. Since there was neither a specific treatment nor a specific vaccine at the time, various pharmaceutical companies—particularly Indian pharmaceutical companies—started developing an effective COVID-19 vaccine. There are many different types of vaccines, including those based on DNA, mRNA, R-DNA technology, proteins, and inactivated viruses-based vaccines. These vaccines are all made by an Indian pharmaceutical business. Following the development, the Indian Council of Medical Research (ICMR), the Drug Controller General of India (DCGI), the Food and Drug Administration, and the WHO approved the use of the vaccine for clinical trials and emergencies. After three trials, an Indian-made vaccine shows high efficacy. The fundamental function of the vaccine is to activate CD8+ cytotoxic T-cells and trigger B-cell clone growth. Lead cytogeneses IL-5 and IL-4 promote IgG antibodies, which strengthen our protection against COVID-19 and its variations.

Public disclosure of clinical trial results at Clinical Trial Registry of India- Need for transparency in research!

Since June 15, 2009, clinical trial registration in the Clinical Trial Registry-India (CTRI) has been made mandatory by the Drugs Controller General of India to improve transparency, accountability, conform to accepted ethical standards and reporting of all relevant results of registered trials. In this study, we planned to evaluate the compliance of Indian and global sponsors with clinical trials conducted in India in terms of reporting of clinical trial results at the CTRI. We included trials registered in the CTRI between January 2018 and January 2020. The CTRI and ClinicalTrials.gov registry was thoroughly searched for all completed interventional studies. A year-wise comparative analysis was performed to evaluate the number of clinical trials reporting results in both the registry. The reporting of completed interventional clinical trial results was 25/112 (22.32%) in year 2018, y, 8/105 (7.6%) in year 2019 and 17/140 (12.14%) in year 2020. There was significantly less reporting of results of Pharmaceutical company sponsored Interventional Studies-Indian at CTRI when compared with ClinicalTrials.gov registry for the year 2019 (odds ratio [OR]-0.17 (95% confidence interval [CI]: 0.08-0.36) and P < 0.0001) and year 2020 (OR-0.45 [95% CI: 0.24-0.82] and P < 0.01). The difference in results reported at CTRI was significantly low for Pharmaceutical company sponsored Interventional Studies-Global only for year 2019 (OR-0.09 [95% CI: 0.005-1.45] and P = 0.04) compared with ClinicalTrials.gov. There is a need to develop the culture of reporting clinical trial results in CTRI to strengthen the transparency in the research for overall benefit of public, health care professionals, and research community.

Preclinical evaluation of safety and immunogenicity of a primary series intranasal COVID-19 vaccine candidate (BBV154) and humoral immunogenicity evaluation of a heterologous prime-boost strategy with COVAXIN (BBV152).

Most if not all vaccine candidates developed to combat COVID-19 due to SARS-CoV-2 infection are administered parenterally. As SARS-CoV-2 is transmitted through infectious respiratory fluids, vaccine-induced mucosal immunity could provide an important contribution to control this pandemic. ChAd-SARS-CoV-2-S (BBV154), a replication-defective chimpanzee adenovirus (ChAd)-vectored intranasal (IN) COVID-19 vaccine candidate, encodes a prefusion-stabilized version of the SARS-CoV-2 spike protein containing two proline substitutions in the S2 subunit. We performed preclinical evaluations of BBV154 in mice, rats, hamsters and rabbits. Repeated dose toxicity studies presented excellent safety profiles in terms of pathology and biochemical analysis. IN administration of BBV154 elicited robust mucosal and systemic humoral immune responses coupled with Th1 cell-mediated immune responses. BBV154 IN vaccination also elicited potent variant (omicron) cross neutralization antibodies. Assessment of anti-vector (ChAd36) neutralizing antibodies following repeated doses of BBV154 IN administration showed insignificant titers of ChAd36 neutralizing antibodies. However, the immune sera derived from the same animals displayed significantly higher levels of SARS-CoV-2 virus neutralization (p<0.003). We also evaluated the safety and immunogenicity of heterologous prime-boost vaccination with intramuscular (IM) COVAXIN-prime followed by BBV154 IN administration. COVAXIN priming followed by BBV154 IN-booster showed an acceptable reactogenicity profile comparable to the homologous COVAXIN/COVAXIN or BBV154/BBV154 vaccination model. Heterologous vaccination of COVAXIN-prime and BBV154 booster also elicited superior (p<0.005) and cross variant (omicron) protective immune responses (p<0.013) compared with the homologous COVAXIN/COVAXIN schedule. BBV154 has successfully completed both homologous and heterologous combination schedules of human phase 3 clinical trials and received the restricted emergency use approval (in those aged above 18 years) from the Drugs Controller General of India (DCGI).

Immunogenicity, reactogenicity and safety of an inactivated quadrivalent influenza vaccine in children and adolescents 6 months through 17 years of age in India

ABSTRACT Efficacy and safety data on quadrivalent influenza vaccines (QIVs) for immunization of Indian children are scarce. This phase 3, registration study evaluated the immunogenicity, safety, and tolerability of a QIV in Indian children aged 6–35 months (Group 1) and 3–17 y (Group 2). Subjects received one or two doses (0.5 mL each) of the study vaccine based on their priming status. Immunogenicity (post-vaccination geometric mean fold increase in hemagglutination inhibition [HI] titers and proportion of patients with seroprotection and seroconversion against the four influenza strains), unsolicited adverse events (AEs), and tolerability were analyzed. Among 118 subjects enrolled in each group, the geometric mean(standard deviation) fold increase in HI titers against A(H3N2), A(H1N1), B(Victoria), and B(Yamagata) strains were 31.7(5.33), 10.5(6.06), 4.1(5.70), and 8.6(5.34) in Group 1 and 14.0(4.37), 9.2(4.26), 14.3(6.73), and 14.4(5.41) in Group 2, respectively. Seroprotection was achieved by 91.2%, 83.3%, 41.2%, and 68.4% subjects in Group 1 and 100%, 95.8%, 73.7%, and 89.8% subjects in Group 2, respectively. Seroconversion was achieved by 87.7%, 66.7%, 41.2%, and 64.9% subjects in Group 1 and 89.0%, 78.8%, 69.5%, and 75.4% subjects in Group 2, respectively. Vaccination site pain and fever were the most common local and systemic reactions, respectively. Systemic reactions were more frequent in Group 1 (16.9% vs 7.6%). Most subjects (>90%) did not experience inconvenience within 7 d of vaccination; <10% in both groups reported unsolicited AEs. Thus, the QIV had a positive benefit/risk profile in Indian children/adolescents aged 6 months to 17 y. CTRI Registry No: CTRI/2018/05/014191 Registry Name: Clinical Trials Registry – India Date of Trial Registration: May 29, 2018 Study Dates: August 03, 2018 (first subject first visit) to January 31, 2019 (last subject last visit) Drugs Controller General of India [DCGI] permission letter number: CT-03/2018