Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202205492711803 Date of Approval: 04/05/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Global Multi-center, Randomized, Blinded, Placebo-controlled Phase 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 Older
Official scientific title A Global Multi-center, Randomized, Blinded, Placebo-controlled Phase 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 Older
Brief summary describing the background and objectives of the trial The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in December 2019 has rapidly become a global epidemic, causing heavy economic stress, medical burden and a serious threat to human survival and health for people worldwide. It is widely believed that effective vaccination plays a crucial role in preventing and controlling the spread of COVID-19. Thus more potent and thermostable vaccine with excellent safety profile is highly-demanded. The investigational vaccine is a linear mRNA molecule obtained by using recombinant gene technology, the safety and immunogenicity of which have been preliminarily evaluated in a phase 1 study in China. In this phase 3 study, we will further confirm its protective efficacy against COVID-19 in some African and Asian countries where the disease is still in pandemic.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 06/11/2022
Actual trial start date 26/01/2023
Anticipated date of last follow up 06/11/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 34000
Actual target sample size (number of participants)
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Crossover: all participants receive all interventions in different sequence during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group placebo placebo 15 months Placebo is 0.9% normal saline purchased from commercial source. 17000 Placebo
Experimental Group LVRNA009 mRNA vaccine 100μg 15 months Investigational vaccine: LVRNA009 is a PBS aqueous end product consisting of mRNA molecule API combined with lipid excipients to form lipid nanoparticles. mRNA molecule has a sequence design length of 4099 bases and a theoretical molecular weight of 1327 kDa. 17000
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
(1) Adults aged 18 years and older. (2) Understand the content of the ICF and the clinical study, and voluntarily sign the ICF (If the participant is unable to sign the ICF on his/her own due to limited literacy, an impartial witness is needed). (3) Participants who are willing and able to comply with study requirements, including all scheduled visits, vaccinations, laboratory tests, and other study procedures. (4) Female participants of childbearing potential or partners of male participants: voluntarily agree to use effective contraception with their partners prior to the first vaccination and must agree to continue such precautions during the study until 3 months after full vaccination(including the initial set of vaccination and crossover set of vaccination). [Effective contraception includes oral contraceptives, injectable or implantable contraception, extended-release topical contraceptives, hormonal patches, intrauterine devices (IUDs), sterilization, abstinence, condoms (for male), diaphragms, cervical caps, etc.]. (5) For female participants: without childbearing potential (amenorrhea for at least 1 year or documented surgical sterilization) or have used effective contraception with a negative pregnancy test before each vaccination in this study (6) During the screening period and within 72 hours prior to the 1st dose, axillary temperatures <37.3°C/99.1°F. (7) Healthy participants or participants with mild underlying disease [in a stable state without exacerbation (no admission to hospital or no major adjustment to treatment regimen, etc.) for at least 3 months prior to enrollment in this study]. 1. History of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), or other coronavirus infections 2. Individuals using prescription medications for prophylaxis or treatment of SARS-CoV-2(including vaccination of licensed COVID-19 vaccines) 3.Previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19 4.History of allergy to any component of the study vaccine or history of severe allergic reaction to vaccine or drug (including but not limited to anaphylaxis, allergic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, or localized allergic necrosis (Arthus reaction)) 5.Positive nucleic acid for SARS-CoV-2 in nasopharyngeal/oropharyngeal swab specimens 6.Positive HIV test results 7.A history or family history of convulsions, epilepsy, encephalopathy and psychosis 8.Malignant tumors in the active phase, not receiving adequate treatment, at potential risk of recurrence during the study 9.Asplenia or functional asplenia, complete or partial splenectomy from any cause. 10.Prolonged (defined as >14 days) use of immunosuppressive or other immunomodulatory drugs (e.g., corticosteroids, ≥20mg/d prednisone or equivalent; however, inhaled and topical steroids are permitted) within 6 months prior to the 1st dose of study vaccine 11.Any other licensed vaccines given within 28 days prior to the study vaccination, or planned administration of vaccine(s) within 28 days after the 2nd dose in the blinded crossover vaccination 12.Have received blood products within 3 months prior to enrollment or plan to receive them during the study. 13.Blood donation or blood loss ≥ 450 mL within 1 month prior to enrollment or planned to donate blood during the study 14.Have received any other investigational product within 1 month prior to enrollment or intent to participate in another clinical study at any time during the study 15.Pregnant or breastfeeding women 16.Deemed unsuitable to participate in this study as assessed by investigator 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/11/2022 The KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
Nairobi Nairobi 254 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 15/11/2022 National Agency for Food and Drug Administration and Control Office of The Director Drug Evaluation and Research Directorate
Ethics Committee Address
Street address City Postal code Country
Plot 1, Isolo Industrial Scheme, Oshodi-Apapa Expressway, Isolo, Lagos Lagos 234 Nigeria
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/09/2022 Uganda National Council for Science and Technology
Ethics Committee Address
Street address City Postal code Country
Plot 6 Kimera Road, Ntinda P.O. Box6884 Kampala, Uganda Kampala 256 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity meeting the case definition for the primary efficacy analysis occurring from 14 days after the 2nd dose in the initial set of vaccination in SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 1. The person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after the 2nd dose of the initial set of vaccination meeting the case definition for the primary efficacy analysis for SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 2. The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2nd dose of the initial set of vaccination meeting the case definition for the primary efficacy analysis for SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 3. The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after the 2nd dose of the initial set of vaccination meeting the case definition for the primary efficacy analysis for SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 4. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2nd dose in the initial set of vaccination for SARS-CoV-2 naive participants at different age strata (18-59 years, ≥ 60 years) in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 5. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2nd dose in the initial set of vaccination for SARS-CoV-2 non-naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 6. The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2nd dose in the initial set of vaccination for SARS-CoV-2 non-naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 7. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2nd dose in the initial set of vaccination regardless prior SARS-CoV-2 infection in the LVRNA009 (50 μg) dose group. 6-12 months
Secondary Outcome 8. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from the 1st dose in the initial set of vaccination in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 9. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 7 days after the 2nd dose in the initial set of vaccination in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 10. The person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after the 2nd dose in the crossover set of vaccination for SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 11. The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after the 2nd dose in the crossover set of vaccination for SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 12. The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after the 2nd dose in the crossover set of vaccination regardless prior SARS-CoV-2 infection in the LVRNA009 (100 μg) dose group 6-12 months
Secondary Outcome 1. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2nd dose in the crossover set of vaccination for SARS-CoV-2 naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 2. The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after the 2nd dose in the crossover set of vaccination for SARS-CoV-2 non-naive participants in the LVRNA009 (100 μg) dose group. 6-12 months
Secondary Outcome 3. The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 of any severity from 14 days after the the 2nd dose caused by individual VOCs in the initial set of vaccination in the LVRNA009 (100 μg) dose group 6-12 months
Secondary Outcome 1. Incidence, intensity and duration of each solicited (local and systemic) AE within 14 days post each dose in reactogenicity subgroup in the initial set of vaccination. (13,600 participants will be assigned into the reactogenicity subgroup (including 13,300 participants in “phase 3” portion of this study)) 14 days post each dose in the initial set of vaccination
Secondary Outcome 2. Incidence, intensity, and causality of AEs occurring 0-28 days post each dose in all participants of each set of vaccinations (initial and crossover). 0-28 days post each dose in the initial and crossover set of vaccination
Secondary Outcome 3. Incidence, intensity, and causality of SAEs, AESIs, and pregnancy events from the day of 1st dose in the initial set of vaccination to 12 months after the 2nd dose in crossover set of vaccination in all participants. from the day of 1st dose in the initial set of vaccination to 12 months after the 2nd dose in crossover set of vaccination
Secondary Outcome 1. Geometric mean titer (GMT) and Geometric mean Increase (GMI) of SARS-CoV-2 virus neutralizing antibody responses and S-protein IgG antibody responses 14 days, 28 days, 3 months and 6 months after the 2nd dose of the 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 2nd dose in the crossover set of vaccination. Baseline,14 days,28 days,3 months and 6 months after the 2nd dose of the initial set of vaccination or the day of crossover vaccination and 28 days,3 months,6 months and 12 months after the 2nd dose
Secondary Outcome 2. The seroconversion rate (SCR) 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 2nd dose of the 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 2nd dose in the crossover set of vaccination. Baseline, 14 days, 28 days, 3 months and 6 months after the 2nd dose of the initial set of vaccination or the day of crossover vaccination and 28 days, 3 months, 6 months 12 months after the 2nd dose
Secondary Outcome 3. The seroconversion rate (SCR) 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 the 2nd dose of the 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 2nd dose in the crossover set of vaccination. Baseline,14days,28 days,3 months and 6 months after the 2nd dose of the initial set of vaccination or the day of crossover vaccination and 28 days,3 months,6 months and 12 months after the 2nd dose
Secondary Outcome 1. The specific cellular immune response (IL-2, IL-4, IL-13, IFN-γ) to SARS-CoV-2 (ELISpot) 7 days, 14 days, 28 days after the 2nd dose of the initial set of vaccination in the cellular immune subgroup. Baseline, 7 days, 14 days, 28 days after the 2nd dose of the initial set of vaccination
Secondary Outcome 2. The cross-neutralizing ability of serum neutralizing antibodies collected 14 days and 28 days after the 2nd dose of the initial set of vaccination in the cross-neutralization subgroup. Baseline, 14 days and 28 days after the 2nd dose of the initial set of vaccination
Secondary Outcome 3. The immunological correlation of risk and protection against symptomatic COVID-19 and SARS-CoV-2 infection after initial set of vaccination. TBD
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI CRDR Research Annex Siaya Site P.O. Box 54840 00200 Off Raila Odinga Way. Nairobi, Kenya. Nairobi Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
AIM Vaccine Co. Ltd Room 218, Xinghai Building,Yingshun Road No.16, Yinghai Township, Daxing District Beijing 100000 China
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor AIM Vaccine Co. Ltd Room 218, Xinghai Building,Yingshun Road No.16, Yinghai Township, Daxing District Beijing 100000 China Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Fan Zhang fan.zhang@aimbio.com 008613671828804 Building 7, 1288 Zhongchun Road, Minhang District
City Postal code Country Position/Affiliation
Shanghai 201100 China Chief Research Officer AIM Vaccine Co. Ltd
Role Name Email Phone Street address
Scientific Enquiries Xi Shao xi.shao@aimbio.com 008618011444241 Building 7, 1288 Zhongchun Road, Minhang District
City Postal code Country Position/Affiliation
Shanghai 201100 China Medical Manager of AIM Vaccine Co. Ltd
Role Name Email Phone Street address
Principal Investigator Videlis Nduba vnduba@gmail.com 25472452247 Behind Posta Offices, Off Posta Road, Kwale, Kenya
City Postal code Country Position/Affiliation
Siaya 144-40600 Kenya Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in journal publication, after deidentification Study Protocol Immediately following publication, No end date Anyone who wishes to access the data with any purpose
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information