PMID- 38076719 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231211 IS - 2772-3682 (Electronic) IS - 2772-3682 (Linking) VI - 19 DP - 2023 Dec TI - Comparison of the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children: an open-label, randomised, multicentre, non-inferiority, parallel-group, phase 3 trial. PG - 100256 LID - 10.1016/j.lansea.2023.100256 [doi] LID - 100256 AB - BACKGROUND: Considering the cholera menace in India and to seek licensure of the oral cholera vaccine (OCV), Euvichol-Plus, we conducted a clinical trial to compare the immunogenicity and safety of Euvichol-Plus with Shanchol in healthy Indian adults and children. METHODS: This phase 3, open-label, multicentre, randomised, non-inferiority, parallel-group, comparative study was conducted at seven sites across India involving 416 healthy adults (aged >/=18-60 years) and children (aged >/=1 to <18 years). Healthy individuals who agreed to participate through a voluntary written informed consent form along with oral or written assent (for children aged 7-18 years) were included. No assent was required for those <7 years, as consent was given by the legally acceptable representatives (LAR). Participants were randomised 1:1 to receive two doses of either Euvichol-Plus or Shanchol orally, 14 days apart. The first dose (1.5 ml) was administered on visit 1, and the second dose at 2 weeks after the first dose during visit 2. Participants were followed up telephonically for 3 consecutive days after each visit and returned for final assessment at 2 weeks after the second dose (visit 3). Blood samples were collected for immunogenicity assessment, and safety analyses were done during all the visits. The primary immunogenicity endpoint was the percentage of participants with >/=4-fold increase in anti-Vibrio cholerae (V. cholerae) O1 Ogawa and O1 Inaba (vibriocidal) antibody titres at 2 weeks after the second dose as compared to baseline titres prior to dosing. The secondary immunogenicity endpoints included the percentage of participants with >/=4-fold increase in anti-V. cholerae O139 antibody titres at 2 weeks after the second dose as compared to baseline titres, and geometric mean titres (GMT) and geometric mean ratios (GMR) as measured by anti-V. cholerae O1 Ogawa, O1 Inaba, and O139 antibody titres at 2 weeks after the second dose as compared to baseline titres. The safety endpoints included assessment of solicited, unsolicited adverse events (AEs), and serious adverse events (SAEs). The clinical trial was registered with the Clinical Trials Registry of India (CTRI/2021/08/035344). FINDINGS: The study was performed in two age cohorts: cohort 1 (aged >/=18-60 years, 208 participants [104 in Euvichol-Plus group and 104 in Shanchol group]), and cohort 2 (aged >/=1 to <18 years, 208 participants [104 in Euvichol-Plus group and 104 in Shanchol group]). A total of 414 participants (Euvichol-Plus: 206 and Shanchol: 208) who completed the study (intention-to-treat and per-protocol set) were analysed to compare the vibriocidal titre as an index for immunogenicity. At 2 weeks after the second dose, the percentage of participants in the Euvichol-Plus group who reported a >/=4-fold increase in anti-V. cholerae antibody titres were 68.93% (O1 Ogawa) [95% CI 62.13%-75.18%], 66.02% (O1 Inaba) [95% CI 59.11%-72.46%], and 59.71% (O139) [95% CI 52.67%-66.47%] as compared to 63.94% (O1 Ogawa) [95% CI 57.01%-70.47%], 65.87% (O1 Inaba) [95% CI 58.99%-72.28%], and 56.25% (O139) [95% CI 49.22%-63.10%] in the Shanchol group. The lower limit of 95% CI for treatment difference for all the antibody titres was >/=10% (non-inferiority margin), demonstrating that Euvichol-Plus was non-inferior to Shanchol. The post-vaccination GMT (Day 14 and 28) were more than the pre-vaccination GMT for all three serotypes in both groups. The GMR obtained for Euvichol-Plus over Shanchol for O1 Ogawa, O1 Inaba, and O139 serotypes was >1, indicating non-inferiority of Euvichol-Plus to Shanchol. The safety cohort included 416 participants. Headache was the most common solicited AE, whereas cold and cough were the most common unsolicited AEs in both groups. INTERPRETATION: Euvichol-Plus appears to be non-inferior to Shanchol in terms of immunogenicity and safety in healthy Indian adults and children. FUNDING: Techinvention Lifecare Private Limited, Mumbai, India. CI - (c) 2023 The Author(s). FAU - Shah, Sanket AU - Shah S AD - Techinvention Lifecare Private Limited, Mumbai, India. FAU - Nandy, Ranjan Kumar AU - Nandy RK AD - Indian Council of Medical Research - National Institute of Cholera and Enteric Diseases, Kolkata, India. FAU - Sethi, Shaily S AU - Sethi SS AD - Techinvention Lifecare Private Limited, Mumbai, India. FAU - Chavan, Bhakti AU - Chavan B AD - Techinvention Lifecare Private Limited, Mumbai, India. FAU - Pathak, Sarang AU - Pathak S AD - Techinvention Lifecare Private Limited, Mumbai, India. FAU - Dutta, Shanta AU - Dutta S AD - Indian Council of Medical Research - National Institute of Cholera and Enteric Diseases, Kolkata, India. FAU - Rai, Sanjay AU - Rai S AD - All India Institute of Medical Sciences, New Delhi, India. FAU - Singh, Chandramani AU - Singh C AD - All India Institute of Medical Sciences, Patna, India. FAU - Chayal, Vinod AU - Chayal V AD - Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India. FAU - Patel, Chintan AU - Patel C AD - Aatman Hospital, Ahmedabad, India. FAU - Kumar, N Ravi AU - Kumar NR AD - Niloufer Hospital, Hyderabad, India. FAU - Chavan, Abhishek T AU - Chavan AT AD - Jeevan Rekha Hospital, Belagavi, India. FAU - Chawla, Amit AU - Chawla A AD - Prakhar Hospital, Kanpur, India. FAU - Singh, Anit AU - Singh A AD - Clinical Research Network India, Noida, India. FAU - Roy, Anupriya Khare AU - Roy AK AD - Clinical Research Network India, Noida, India. FAU - Singh, Nidhi AU - Singh N AD - Clinical Research Network India, Noida, India. FAU - Baik, Yeong Ok AU - Baik YO AD - EuBiologics Co., Ltd., Seoul, South Korea. FAU - Lee, Youngjin AU - Lee Y AD - EuBiologics Co., Ltd., Seoul, South Korea. FAU - Park, Youngran AU - Park Y AD - EuBiologics Co., Ltd., Seoul, South Korea. FAU - Jeong, Kyung Ho AU - Jeong KH AD - EuBiologics Co., Ltd., Seoul, South Korea. FAU - Ahmed, Syed AU - Ahmed S AD - Techinvention Lifecare Private Limited, Mumbai, India. LA - eng PT - Journal Article DEP - 20230824 PL - England TA - Lancet Reg Health Southeast Asia JT - The Lancet regional health. Southeast Asia JID - 9918419282806676 PMC - PMC10709676 OTO - NOTNLM OT - Cholera OT - Euvichol-Plus OT - Immunogenicity OT - India OT - Non-inferiority OT - Oral cholera vaccines OT - Phase 3 OT - Safety OT - Shanchol COIS- SD and RKN are affiliated with ICMR-NICED, Kolkata. A memorandum of agreement was signed between Techinvention Lifecare Private Limited and ICMR-NICED. Laboratory analysis was carried under collaborative project between ICMR-NICED, Kolkata, and Techinvention Lifecare Private Limited, Mumbai. Fund provided by Techinvention Lifecare Private Limited was received by ICMR-NICED for carrying out bioanalytic testing at ICMR-NICED. All other authors have no competing interests. EDAT- 2023/12/11 12:43 MHDA- 2023/12/11 12:44 PMCR- 2023/08/24 CRDT- 2023/12/11 06:15 PHST- 2023/01/24 00:00 [received] PHST- 2023/05/08 00:00 [revised] PHST- 2023/07/19 00:00 [accepted] PHST- 2023/12/11 12:44 [medline] PHST- 2023/12/11 12:43 [pubmed] PHST- 2023/12/11 06:15 [entrez] PHST- 2023/08/24 00:00 [pmc-release] AID - S2772-3682(23)00116-6 [pii] AID - 100256 [pii] AID - 10.1016/j.lansea.2023.100256 [doi] PST - epublish SO - Lancet Reg Health Southeast Asia. 2023 Aug 24;19:100256. doi: 10.1016/j.lansea.2023.100256. eCollection 2023 Dec.