| Protocol No: | ECCT/22/08/02 | Date of Protocol: | 02-04-2022 |
| Study Title: | A Global Multi-center, Randomized, Blinded, Placebo-controlled Phase 2/3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (LVRNA009) for the Prevention of COVID-19 in Participants Aged 18 Years and Olde |
| Study Objectives: | Primary efficacy objective: To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participant Secondary efficacy objectives: 1. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. 2. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. 3. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. 4. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 naive participants in different age strata (18-59 years old and ≥ 60 years old). 5. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 non-naive participants. 6. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after 2 nd dose in the initial set of vaccination in SARS-CoV-2 non-naive participants. 7. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases COVID-19 of any severity occurring from 14 days after 2 nd dose in the initial set of vaccination regardless of evidence of prior SARS-CoV-2 infection. 8. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from the day of the 1 st dose in the initial set of vaccination. 9. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 7 days after the 2 nd dose in the initial set of vaccination. 10. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 naive participants. 11. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 naive participants. 12. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after the 2 nd dose in the crossover set of vaccination regardless of evidence of prior SARS-CoV-2 infection Secondary safety objectives: 1. To assess the solicited AEs (local and systemic) occurring 0-14 days post each dose in the reactogenicity subgroup in the initial set of vaccination. 2. To assess the AEs occurring 0-28 days post each dose in all participants of each set of vaccinations (initial and crossover). 3. To assess SAE, AESI, pregnancy events from 1 st dose in the initial set of vaccination to 12 months after the the 2 nd dose in the crossover set of vaccination Secondary immunogenicity objectives (for immunogenicity subgroup): 1. To assess the SARS-CoV-2 virus neutralizing antibody responses and S-protein IgG antibodies responses 14 days, 28 days, 3 months and 6 months after the 2nddose of initial set of vaccination or the day of crossover vaccination (whichever come earlier), 28 days, 3 months, 6 months and 12 months after the the 2 nd dose in the crossover set of vaccination. 2. To assess the seroconversion of SARS-CoV-2 virus neutralizing antibody and S-protein IgG antibodies in seronegative participants at baseline, 14 days, 28 days, 3 months and 6 months after 2 nd dose of initial set of vaccination or the day of crossover vaccination (whichever comes earlier), and 28 days, 3 months, 6 months and 12 months after the the 2 nd dose in the crossover set of vaccination. 3. To assess the 4-fold rise response of SARS-CoV-2 virus neutralizing antibody and S-protein IgG antibodies in seropositive participants at baseline, 14 days, 28 days, 3 months and 6 months after 2 nd dose of initial set of vaccination or the day of crossover vaccination (whichever comes earlier), and 28 days, 3 months, 6 months and 12 months after the 2 nd dose in the crossover set of vaccination Exploratory efficacy objectives: 1. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 naive participants. 2. To evaluate the protective efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2 nd dose in the crossover set of vaccination in SARS-CoV-2 non-naive participants. 3. To demonstrate the efficacy of LVRNA009 (50 μg) in the prevention of first episodes of virologically-confirmed cases of COVID-19 of any severity from 14 days after the 2 nd dose caused by individual VOCs in the initial set of vaccination Exploratory immunogenicity objectives (for immunogenicity subgroup): 1. To assess the specific cellular immune response 7 days, 14 days, 28 days after the 2 nd dose of initial set of vaccination in the cellular immune subgroup. 2. To assess the cross-neutralizing ability of serum neutralizing antibodies collected 14 days and 28 days after the the 2 nd dose of initial set of vaccination.in cross-neutralization subgroup. 3. To evaluate the immunological correlation of risk and protection against symptomatic COVID-19 and SARS-CoV-2 infection after the initial set of vaccination. |
| Laymans Summary: | The existence of a severe respiratory illness in Wuhan City, Hubei Province, China in December 2019 led to the discovery of a unique type of germs called coronavirus. This type of germs is a virus which causes a flu-like illness called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) or COVID-19 in the human population. The outbreak led to its announcement on 30 January 2020 by the World Health Organization (WHO) as a Public Health Emergency of International Concern and later declared on 11 March 2020 as a pandemic. It presents as a mild illness in most cases and some individuals may be asymptomatic. The symptoms include cough and shortness of breath, diarrhoea and nausea, loss of smell and taste. More severe symptoms include sudden onset and severe difficulty in breathing` requiring assisted breathing while in some cases it causes death. Most symptoms resolve on their own, such as fatigue and difficulty breathing but may appear to persist for up to 2 months after illness onset despite clearance of the virus. Research shows that adults over 50 years of age and individuals with chronic medical conditions are at a higher risk of bad outcomes and even death. As of July 19th 2022, The Ministry of Health, Kenya reported that a total of 19,148,223 vaccines had been administered across the country. Of these, 16,944,531 were doses administered to the adult population (18 years and above). Another 1,575,736 were doses administered to those between 15 to 17 years, 48,415 were below 15 years but above 12 years while 579,541 were booster doses. Proportion of adults fully vaccinated was 32.3%. The Government was working towards vaccinating a targeted population of 27,246,033.Despite measures of isolation, quarantine, social distancing, community containment, mask wearing, hand washing and sanitization, and the rapid development and global deployment of multiple authorized COVID-19 vaccines, the worldwide burden of COVID-19 infections and associated disease remains large. |
| Abstract of Study: | Background The outbreak of SARS-CoV-2 infection has rapidly become a global epidemic, causing heavy economic stress, medical burden and a serious threat to human survival and health for people worldwide. SARS-CoV2 is transmitted primarily by respiratory droplets and close contact. Based on current epidemiological investigations, the incubation period for the onset of SARS-CoV-2 infection is 1-14 days, mostly 3-7 days. Fever, dry cough and malaise are the main manifestations. In the current absence of effective treatments, effective vaccination plays a crucial role in preventing and controlling the spread of COVID-19. LVRNA009 is a SARS-CoV-2 mRNA vaccine obtained by using recombinant gene technology to construct and produce linearized vectors, synthesizing mRNA molecules through in vitro enzyme-catalyzed technology, purification, and formulation process. Objective To evaluate the protective efficacy of LVRNA009 (50μg) in the prevention of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after 2nd dose in the initial set of vaccination in SARS-CoV-2 naive participants. Methodology This is a global Phase2/3, multi-center, randomized, blinded, placebo-controlled study followed by blinded crossover vaccination, to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 mRNA vaccine (LVRNA009) against COVID-19 in participants aged 18 years and older. Participants will be randomized in a 1:1 ratio to receive 1 dose of the study vaccine or placebo on Day 0 and Day 28. Site Activities will be conducted in Siaya at the Siaya Referral Hospital grounds; Siaya Clinical Research Annex.. This is a global study that plans to enroll 300 participants for Phase 2 and about 33,700 participants aged 18 years and older will be included in “Phase 3” portion, and about 10%-20% of participants aged 60 years and older will be included. The Siaya Clinical Research Annex is targeting to recruit at least 1000 Participants. Expected Application of Results The study vaccine will provide protection against symptomatic COVID-19 in healthy adults aged 18 years and older. |