The Lancet Regional Health - Southeast Asia (Mar 2023)
Safety and immunogenicity of SII-NVX-CoV2373 (COVID-19 vaccine) in adults in a phase 2/3, observer-blind, randomised, controlled studyResearch in context
- Prasad S. Kulkarni,
- Abhijit Kadam,
- Sheela Godbole,
- Varsha Bhatt,
- Abhishek Raut,
- Sunil Kohli,
- Santanu Tripathi,
- Praveen Kulkarni,
- Rakhi Ludam,
- Madhav Prabhu,
- Ashish Bavdekar,
- Nithya J. Gogtay,
- Sushant Meshram,
- Tamilarasu Kadhiravan,
- Sonali Kar,
- D.H. Ashwath Narayana,
- Clarence Samuel,
- Govind Kulkarni,
- Abhay Gaidhane,
- Dipu Sathyapalan,
- Sidram Raut,
- Vijay Hadda,
- Hira Lal Bhalla,
- Chetanraj Bhamare,
- Abhijeet Dharmadhikari,
- Joyce S. Plested,
- Shane Cloney-Clarke,
- Mingzhu Zhu,
- Melinda Pryor,
- Stephanie Hamilton,
- Madhuri Thakar,
- Ashwini Shete,
- Manish Gautam,
- Nivedita Gupta,
- Samiran Panda,
- Umesh Shaligram,
- Cyrus S. Poonawalla,
- Balram Bhargava,
- Bhagwat Gunale,
- Dhananjay Kapse,
- Shubhangi A. Kanitkar,
- Arjun L. Kakrani,
- Srikanth P. Tripathy,
- Abhijit V. Tilak,
- Akshay A. Dhamne,
- Shahzad Beg Mirza,
- Prachi V. Athavale,
- Mandakini Bhowmik,
- Parag J. Ratnakar,
- Subodh Gupta,
- Vijayshri Deotale,
- Jyoti Jain,
- Ashwini Kalantri,
- Vineet Jain,
- Nidhi Goyal,
- Alok Arya,
- Temsunaro Rongsen-Chandola,
- Shreyasi Dasgupta,
- Pratibha Periera,
- Vanmathi A,
- Anand Kawade,
- Arunkumar Gondhali,
- Palvi Kudyar,
- Abhishek Singh,
- Ravi Yadav,
- Alina Alexander,
- Venugopalan Gunasekaran,
- Sekar Dineshbabu,
- P.C. Samantaray,
- H.S. Ravish,
- Deepshikha Kamra,
- Shilpa Gaidhane,
- Quazi Syed Zahiruddin,
- Merlin Moni,
- Anil Kumar,
- Ameet Dravid,
- Anant Mohan,
- Tejas Suri,
- Tejas K. Patel,
- Surekha Kishore,
- Rahul Choche,
- Deepak Ghatage,
- Sugam Salvi
Affiliations
- Prasad S. Kulkarni
- Serum Institute of India Pvt Ltd, Pune, India; Corresponding author: Serum Institute of India Pvt Ltd, Poonawalla Biotechnology Park SEZ, Manjari (Bk), Pune, 412307, India.
- Abhijit Kadam
- Indian Council of Medical Research-National AIDS Research Institute, Pune, India
- Sheela Godbole
- Indian Council of Medical Research-National AIDS Research Institute, Pune, India
- Varsha Bhatt
- Dr. D. Y. Patil Medical College Hospital and Research Centre, Pune, India
- Abhishek Raut
- Mahatma Gandhi Institute of Medical Sciences, Sewagram, Wardha, India
- Sunil Kohli
- Hamdard Institute of Medical Sciences and Research, New Delhi, India
- Santanu Tripathi
- Calcutta Medical College, Kolkata, India
- Praveen Kulkarni
- JSS Academy of Higher Education and Research, Mysore, India
- Rakhi Ludam
- Institution of Medical Science and SUM Hospital, Bhubaneswar, India
- Madhav Prabhu
- KLES Dr. Prabhakar Kore Hospital and Medical Research Center, Belgavi, India
- Ashish Bavdekar
- KEM Hospital Research Centre, Vadu Budruk, Pune, India
- Nithya J. Gogtay
- Seth G S Medical College and KEM Hospital, Mumbai, India
- Sushant Meshram
- Government Medical College, Nagpur, India
- Tamilarasu Kadhiravan
- Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
- Sonali Kar
- Kalinga Institute of Medical Sciences, Bhubaneswar, India
- D.H. Ashwath Narayana
- KIMS Hospital and Research Centre, Bengaluru, India
- Clarence Samuel
- Christian Medical College and Hospital, Ludhiana, India
- Govind Kulkarni
- Sahyadri Super Speciality Hospital, Pune, India
- Abhay Gaidhane
- Acharya Vinoba Bhave Rural Hospital and Datta Meghe Institute of Medical Sciences, Sawangi (M), Wardha, India
- Dipu Sathyapalan
- Amrita Institute of Medical Sciences, Kochi, India
- Sidram Raut
- Noble Hospital, Pune, India
- Vijay Hadda
- All India Institute of Medical Sciences, New Delhi, India
- Hira Lal Bhalla
- All India Institute of Medical Sciences, Gorakhpur, India
- Chetanraj Bhamare
- Serum Institute of India Pvt Ltd, Pune, India
- Abhijeet Dharmadhikari
- Serum Institute of India Pvt Ltd, Pune, India
- Joyce S. Plested
- Clinical Immunology Laboratory, Novavax, Gaithersburg, MD, USA
- Shane Cloney-Clarke
- Clinical Immunology Laboratory, Novavax, Gaithersburg, MD, USA
- Mingzhu Zhu
- Clinical Immunology Laboratory, Novavax, Gaithersburg, MD, USA
- Melinda Pryor
- 360biolabs, 85 Commercial Road, Melbourne, Victoria, Australia
- Stephanie Hamilton
- 360biolabs, 85 Commercial Road, Melbourne, Victoria, Australia
- Madhuri Thakar
- Indian Council of Medical Research-National AIDS Research Institute, Pune, India
- Ashwini Shete
- Indian Council of Medical Research-National AIDS Research Institute, Pune, India
- Manish Gautam
- Serum Institute of India Pvt Ltd, Pune, India
- Nivedita Gupta
- Indian Council of Medical Research, New Delhi, India
- Samiran Panda
- Indian Council of Medical Research, New Delhi, India
- Umesh Shaligram
- Serum Institute of India Pvt Ltd, Pune, India
- Cyrus S. Poonawalla
- Serum Institute of India Pvt Ltd, Pune, India
- Balram Bhargava
- Indian Council of Medical Research, New Delhi, India
- Bhagwat Gunale
- Serum Institute of India Pvt Ltd, Pune, India
- Dhananjay Kapse
- Serum Institute of India Pvt Ltd, Pune, India
- Shubhangi A. Kanitkar
- Arjun L. Kakrani
- Srikanth P. Tripathy
- Abhijit V. Tilak
- Akshay A. Dhamne
- Shahzad Beg Mirza
- Prachi V. Athavale
- Mandakini Bhowmik
- Parag J. Ratnakar
- Subodh Gupta
- Vijayshri Deotale
- Jyoti Jain
- Ashwini Kalantri
- Vineet Jain
- Nidhi Goyal
- Alok Arya
- Temsunaro Rongsen-Chandola
- Shreyasi Dasgupta
- Pratibha Periera
- Vanmathi A
- Anand Kawade
- Arunkumar Gondhali
- Palvi Kudyar
- Abhishek Singh
- Ravi Yadav
- Alina Alexander
- Venugopalan Gunasekaran
- Sekar Dineshbabu
- P.C. Samantaray
- H.S. Ravish
- Deepshikha Kamra
- Shilpa Gaidhane
- Quazi Syed Zahiruddin
- Merlin Moni
- Anil Kumar
- Ameet Dravid
- Anant Mohan
- Tejas Suri
- Tejas K. Patel
- Surekha Kishore
- Rahul Choche
- Deepak Ghatage
- Sugam Salvi
- Journal volume & issue
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Vol. 10
p. 100139
Abstract
Summary: Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13–22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.
