A two-and-a-half-day workshop on regulatory and ethical issues in first-in-human (FIH) clinical trials in India was held at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India, on 7–9 November 2024, under the aegis of the Indian Council of Medical Research (ICMR) Phase I Network. The workshop brought together regulators, academic investigators, and industry representatives to examine the evolving regulatory landscape of early phase trials in India and the operational challenges associated with it. Through interactive sessions, including preparation of investigational new drug (IND) application, mock pre-IND/IND and mock subject expert committee (SEC) meetings, on-site monitoring simulations, and structured hands-on exercises, the workshop navigated regulatory submission pathways, trial reporting, documentation standards, safety oversight, and informed consent processes. A panel discussion on the phase lag policy for FIH studies in India was held with expert personnel from regulatory agencies, ICMR headquarters, industry, and academia. The workshop discussions underscored the need for policy harmonization, enhanced site preparedness, and sustained capacity-building to position India as a leader for early phase clinical research. The present article summarizes the proceeding of the workshop and highlights the critical insights for developing a regulatory and ethical framework to support FIH trials in India.
Background: A novel nanosomal paclitaxel lipid suspension (NPLS), free from Cremophor EL (CrEL) and ethanol, was developed to address the solvent-related toxicities associated with conventional paclitaxel formulation. Objective: To evaluate the efficacy and safety of NPLS versus CrEL-based paclitaxel (conventional paclitaxel) in patients with metastatic breast cancer (MBC). Design: A prospective, open-label, randomized, multiple-dose, parallel, phase II/III study. Methods: Adult (18–65 years) female patients with MBC who had previously failed at least one line of chemotherapy were randomized (2:2:1) to NPLS 175 mg/m2 every 3 weeks (Q3W, n = 48, arm A), NPLS 80 mg/m2 every week (QW, n = 45, arm B) without premedication or conventional paclitaxel (Taxol®, manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m2 Q3W ( n = 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A ( n = 37) or arm C ( n = 17). Results: Pooled data from the primary study and its extension phase included 174 patients. The primary endpoint was the overall response rate (ORR). As per intent-to-treat analysis, ORR was significantly better in the NPLS QW arm as compared to conventional paclitaxel [44.4% (20/45) versus 22.7% (10/44), ( p = 0.04)]. An improvement in ORR with NPLS Q3W versus conventional paclitaxel arm [29.4% (25/85) versus 22.7% (10/44)] ( p = 0.53) was observed. Disease control rates observed were improved with NPLS Q3W versus conventional paclitaxel Q3W (77.7% versus 72.7%, p = 0.66) and with NPLS QW versus conventional paclitaxel Q3W (84.4% versus 72.7%, p = 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W versus conventional paclitaxel Q3W arms. Conclusion: NPLS demonstrated an improved tumor response rate and a favorable safety profile versus conventional paclitaxel. NPLS 80 mg/m2 QW demonstrated a significantly better response versus conventional paclitaxel 175 mg/m2 Q3W. Trial registration: Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062)
Background: To assess safety and tolerability of a diphtheria and tetanus toxoid, acellular pertussis, inactivated poliovirus and Haemophilus influenza type B conjugate adsorbed vaccine (DTaP-IPV + Hib), manufactured by Serum Institute of India Pvt. Ltd. (SIIPL)'s, the current first-in-human Phase 1 study was conducted in healthy adults. Methods: Vaccine was administered as a single 0.5 mL dose intramuscularly into deltoid muscle of 24 healthy adults aged 18-45 years, who were then followed prospectively for one month for safety outcomes.Results: All 24 participants completed the study in compliance with protocol. Four solicited adverse events were reported in three participants during the study; all adverse events were mild and recovered completely. No deaths, unsolicited adverse events, or serious adverse events were reported.Conclusion: SIIPL DTaP-IPV + Hib vaccine was well tolerated and safe in study subjects. Further clinical development will be conducted to assess safety and immunogenicity in young children, the target population. Clinical Trial Registration: CTRI/2017/07/009034. (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Vaginal yeast infection is one of the most common diseases caused by vulvovaginal candidiasis (VVC). Effective therapy for VVC is needed. A lipid-based amphotericin B gel 0.1% (LAB) was developed and evaluated for the treatment of VVC patients and those who failed to azole therapy. LAB was applied topically twice daily for 7 days to 64 moderate patients and 14 days to 55 severely infected VVC patients. Additionally, 66 patients who failed to azole therapy were treated twice daily with LAB for 14 days. A 91.5% clinical response and 93.16% mycological response was observed in VVC patients. The patients treated with LAB who failed to azole therapy showed a 75% clinical, 95.3% mycological response and 83% remission was observed. Overall, the LAB was found to be efficacious and safe for the treatment of VVC patients. Clinical Trial Registration All the trials were registered at Clinical Trial Registry of India (CTRI/2013/02/003378, CTRI/2014/02/004409).
