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.: PACTR202112597608463 Date of Approval: 14/12/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Phase I/II Study to Evaluate the Safety, Reactogenicity and Immunogenicity of RBD SARS-CoV-2 HBsAg VLP Vaccine in Healthy Adults.
Official scientific title A Phase I/II Study to Evaluate the Safety, Reactogenicity and Immunogenicity of RBD SARS-CoV-2 HBsAg VLP Vaccine in Healthy Adults.
Brief summary describing the background and objectives of the trial The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as global pandemic and public health emergency of international concern. As the Covid-19 pandemic evolves, a number of variants of concern and high significance have emerged. These include the B1.1.7 (UK variant), B.1.351 (South African (SA) variant), B.1.427 and B.1.429 (California variants) and P.1 (Brazil) variants. The most pertinent to southern Africa and Zimbabwe at the present moment is the B.1.351 variant that is circulating in Zimbabwe. Many of these variants include changes in the receptor binding (RBD) domain. Binding of the RBD to the Angiotensin Converting Enzyme (ACE)-2 receptor facilitates entry of the virus into human cells. Vaccine-induced antibodies can block binding of the virus RBD to the receptor and prevent viral entry and infection. Mutations in the RBD can alter neutralizing activity of these vaccine-induced antibodies, requiring that new vaccines be developed to respond to the variants. Developing vaccine platforms that are cost-effective and can neutralize emerging variants such as the South African variant will be important for achieving vaccine-mediated viral control. We intend to conduct a Phase I/II open-label, randomized, active-controlled clinical trial to primarily evaluate the safety, reactogenicity and immunogenicity of a bivalent (Wuhan and South African variants) RBD SARS-CoV-2 HBsAg VLP vaccines with either SWE or Aluminum adjuvant, in a dose escalation study in healthy adults aged at least 18 years. We will also assess their cellular immune response (CD4 + and CD8+ T-cell responses)
Type of trial RCT
Acronym (If the trial has an acronym then please provide) ZimCovax
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 07/12/2021
Actual trial start date
Anticipated date of last follow up 30/10/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 350
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
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
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Covishield Vaccine 0.5 mls administered via intramuscular injection ; Two doses, given on Day 0 (Visit 2) and Day 28 (Visit 5) COVISHIELD™ is a monovalent vaccine composed of a single recombinant, replication-deficient chimpanzee adenovirus (ChAdOx1) vector encoding the S glycoprotein of SARS-CoV-2. Following administration, the S glycoprotein of SARS-CoV-2 is expressed locally stimulating neutralizing antibody and cellular immune responses. 50 Active-Treatment of Control Group
Experimental Group RBD vaccine with SWE adjuvant 0.5mls, containing 1.25µg of the RBD vaccine with SWE adjuvant To be administered via intramuscular injection on Day 0 and a Booster dose at Day 180 (Schedule A) RBD SARS-CoV-2 Ag Spytag conjugated to HBsAg VLP Spycatcher 50
Experimental Group RBD vaccine with SWE adjuvant 0.5mls, containing 2.5µg of the RBD vaccine with SWE adjuvant To be administered via intramuscular injection on Day 0 and a Booster dose at Day 180 (Schedule A) RBD SARS-CoV-2 Ag Spytag conjugated to HBsAg VLP Spycatcher 50
Experimental Group RBD vaccine with SWE adjuvant 0.5mls, containing 1.25µg of the RBD vaccine with SWE adjuvant. To be administered via intramuscular injection on Day 0, Day 28 and a Booster dose at Day 180 (Schedule B) RBD SARS-CoV-2 Ag Spytag conjugated to HBsAg VLP Spycatcher 50
Experimental Group RBD vaccine with SWE adjuvant 0.5mls, containing 2.5µg of the RBD vaccine with SWE adjuvant To be administered via intramuscular injection on Day 0, Day 28 and a Booster dose at Day 180 (Schedule B) RBD SARS-CoV-2 Ag Spytag conjugated to HBsAg VLP Spycatcher 50
Experimental Group RBD vaccine with Aluminium hydroxide adjuvant 0.5mls, containing 10µg of the RBD vaccine with Aluminium hydroxide adjuvant To be administered via intramuscular injection on Day 0, Day 28 and Day 56 (Schedule C) RBD SARS-CoV-2 Ag Spytag conjugated to HBsAg VLP Spycatcher 50
Experimental Group RBD vaccine with Aluminium hydroxide adjuvant 0.5mls, containing 25µg of the RBD vaccine with Aluminium hydroxide adjuvant To be administered via intramuscular injection on Day 0, Day 28 and Day 56 (Schedule C) RBD SARS-CoV-2 Ag Spytag conjugated to HBsAg VLP Spycatcher 50
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Male or Female aged above 18 years (inclusive) Phase I: Participants aged 18 to 45 years (both inclusive) Phase II: Participants aged above 18 years (inclusive) (Strata 1: 18 to 59 years (both inclusive), Strata 2: above 60 years (inclusive). Healthy participants as determined by medical history, physical examination, vital signs and clinical and laboratory examination. Test negative for SARS-CoV-2 infection by RT-PCR test at screening Test negative for -SARS-CoV-2 IgG antibody by serology test at screening Capable and willing to provide written informed consent prior to the performance of any study-specific procedures. Receipt of medications or vaccines intended to prevent or treat COVID-19 infection in the past. Fever (non-axillary temperature > 37.5 ºC) or any other symptoms of infection that have not completely resolved including respiratory symptoms/illnesses within the past 3 days from randomization (Day 0) Participants with a BMI > 35 kg/m2. A major or clinically significant medical condition. Individuals currently working in occupations with high risk of exposure to SARS-CoV Pregnant or lactating women or willingness/intention to become pregnant during the study. History of allergy to any component of the RBD SARS-CoV-2 HBsAg VLP Vaccine, or serious adverse reactions to the vaccine A history of anaphylaxis to a vaccine, food, drug, toxin or other exposure Known hypersensitivity reactions to yeast. Positive test result at screening for HIV ½ antibody, HBsAg or HCV Ab Clinical laboratory tests of blood and urine not within the normal range and show clinically relevant deviations as judged by the Investigator. History of demyelinating disease or Guillain Barre syndrome Eczema or other significant skin lesion or infection at the site/s of vaccination Planned or actual receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination Positive screen for drugs of abuse or alcohol (breath test) at screening and randomization (Day 0). (Drugs of abuse include amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, and tetrahydrocannabinol). Participants who currently smoke at least 10 cigarettes or equivalent per day Receipt of blood/blood products/immunoglobulins or donation of blood/blood products 8 weeks prior to vaccination or planned receipt or donation during the study period Any other medical condition which in the opinion of the Investigator may affect the subject’s safety or study participation and conduct. 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 11/08/2021 Medical Research Council of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
Corner Josiah Tongogara and Mazowe Street Harare 00263 Zimbabwe
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 11/10/2021 Medicines Control Authority of Zimbabwe
Ethics Committee Address
Street address City Postal code Country
106 Baines Avenue Harare 00263 Zimbabwe
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety and reactogenicity Throughout the study
Secondary Outcome Immunogenicity Schedule A: Day 0, 28, 42, 56, 84, 180, 208 and 270/ Schedule B: Day 0, 28, 42, 56, 84, 180, 208 and 270/ Schedule C: Day 0, 28, 42, 56, 70, 84 and 180/ Active control: Day 0, 28, 42, 56, 84 and 180.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
St Annes Hospital 155, King George Road, Avondale, Harare. Harare Zimbabwe
Citimed Chitungwiza Hospital 14656, Hadzinanhanga Road, Zengeza 4 Chitungwiza Zimbabwe
Mbuya Dorcas Hospital 3639, Masotsha Ndhlovu Way Harare Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
Serum Institute of India 2122, Off Soli Poonawalla Road, Hadapsar Pune 411028 India
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Serum Institute of India 212/2, Off Soli Poonawalla Road, Hadapsar Pune 411028 India Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Tariro Azure Makadzange tariro.makadzange@crmgresearch.com +263772434166 155 King George Road, Avondale.
City Postal code Country Position/Affiliation
Harare Zimbabwe CEO and Founder of Charles River Medical Group
Role Name Email Phone Street address
Public Enquiries Tariro Makadzange tariro.makadzange@crmgresearch.com +263772434166 155 King George Road, Avondale
City Postal code Country Position/Affiliation
Harare Zimbabwe CEO and Founder of Charles River Medical Group
Role Name Email Phone Street address
Scientific Enquiries Tariro Makadzange tariro.makadzange@crmgresearch.com +263772434166 155 King George Road, Avondale
City Postal code Country Position/Affiliation
Harare Zimbabwe CEO and Founder of Charles River Medical Group
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary data will be shared. No individual participant data sharing is anticipated at this time. Statistical Analysis Plan Within 12 months of last participant last visit Controlled access.
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