COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral Platform in Healthy South African Adults

Study Overview
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Brief Summary
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This is a phase 1b, open-label study in adult healthy participants. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of the hAd5-S-Fusion+N-ETSD vaccine and select a dose for future studies.

Official Title
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Phase 1b Open-Label Study of the Safety, Reactogenicity, and Immunogenicity of a Prophylactic COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral Platform in Healthy South African Adults (ProVIVA-SA-1)

Conditions
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Covid19

Intervention / Treatment
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* Biological: hAd5-S-Fusion+N-ETSD vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Adults, age 18 - 50 years, inclusive, at time of first study vaccination. Able to understand and provide a signed informed consent that fulfils the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. Agrees to the collection of biospecimens (e.g. nasopharyngeal [NP] swabs) and venous blood per protocol. Ability to attend required study visits and return for adequate follow-up, as required by this protocol. Body mass index (BMI) < 30.00 kg/m2 Temperature < 38.0°C on day of first study vaccination. Good general health as shown by medical history, physical exam, and screening laboratory tests Screen negative for Tuberculosis per local screening guidelines Male participants should all be at low risk of HIV acquisition based on pre-specified, validated criteria(Laher 2014) i.e. answering YES to any of the following questions: 1. Are you sexually abstinent? 2. Are you in a mutually monogamous relationship with a known HIV-uninfected partner? 3. Have you had only one partner in the preceding 12 months who is believed to be HIV-uninfected and with whom condoms were used regularly? Laboratory Inclusion Values/ Results: 10. Alanine aminotransferase (ALT) <1.1 times the upper limit of normal 11. Serum Creatinine <80 umol/L in females and <106 umol/L in males 12. Haemoglobin >12.0g/dL in females and >13.5g/dL in males 13. Platelets >150 x 109/L in all participants 14. No serological evidence of chronic infection with Hepatitis B (hepatitis B surface antigen (HepBSAg) negative by a locally approved assay) done during the screening period 15. No serological evidence of chronic infection with Hepatitis C (hepatitis C antibody(anti-HCV) negative by a locally approved assay) done during the screening period 16. Negative for SARS-CoV-2 (qPCR test) on NP swab(or other appropriate respiratory specimen) within 3 days prior to the first study vaccination 17. No serological evidence of prior infection with SARS-CoV-2 (by a locally approved assay) done during the screening period 18. A negative serum or urine pregnancy test during screening and on the day of and prior to each dose must be documented before the vaccine is administered to a female participant. 19. Negative for HIV-1 and -2 on blood test(by either 2 rapid tests or an ELISA, both must be locally approved assays) done during the screening period. Reproductive Status: 20. Female participants of childbearing potential must agree to use effective contraception for sexual activity that may lead to pregnancy while on study until at least 30 days after the last dose of the study vaccine. Effective contraception for female participants includes: Intrauterine device (IUD), or Hormonal contraception (oral/ injectable/ implant/ transdermal etc.) Or; 21. Non-sterile male participants must agree to use a condom while on study until at least 30 days after the last dose of the study vaccine. Or; 22. Participant must not be of reproductive potential or sterile(as verified by medical records), such as: Having been diagnosed with menopause(with no menses for 1 year) Having undergone hysterectomy, bilateral oophorectomy or orchidectomy Having undergone surgical sterilization (e.g., vasectomy, tubal ligation) Exclusion Criteria: A history of illness compatible with COVID-19 disease since March 2020. Serious adverse reaction to any vaccine, any unrelated medication or any component of the investigational vaccine, including a history of anaphylaxis and symptoms of a severe allergic reaction and history of allergies in the past. Pregnant or breastfeeding women. Live in a nursing home or long-term care facility. Chronic lung disease or moderate to severe asthma. Bone marrow or organ transplantation recipients. Diabetes. Chronic kidney disease undergoing dialysis. Liver disease. Any disease associated with acute fever, or any infection. Self-reported history of severe acute respiratory syndrome (SARS). Chronic hepatitis B or hepatitis C infection. HIV positive or other acquired or hereditary immunodeficiency. Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension without controllable drugs, etc. History of hereditary, idiopathic or acquired angioedema. Urticaria in the last 12 months prior to screening. No spleen or functional asplenia. Platelet disorder or other bleeding disorder that may cause injection contraindication. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness. (Including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators. The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted.) Prior administration of blood products within 120 days before first study vaccination. Prior administration of other research medicines or investigational product within 30 days before first study vaccination. Prior administration of attenuated vaccine within 30 days before first study vaccination.. Prior administration of inactivated vaccine within 14 days before first study vaccination. Current treatment with investigational agents for prophylaxis of COVID-19. Have a household contact that has been diagnosed with COVID-19 within 14 days before fist study vaccine. Current anti-tuberculosis prophylaxis or therapy. Currently receiving treatment for cancer or history of cancer in the last five years (except basal cell carcinoma of the skin and cervical carcinoma in situ). According to the judgement of investigator any medical, psychiatric, psychological, social, occupational or other conditions that could affect the participants ability to sign informed consent, provide safety assessment data or comply with the requirements of the study protocol. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (n = 10): hAd5-S-Fusion+N-ETSD at 5 × 10e10 Viral Particles (VP) per dose<br>hAd5-S-Fusion+N-ETSD at 5 × 10e10 Viral Particles (VP) per dose on Days 1 and 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* The hAd5-S-Fusion+N-ETSD vaccine is a hAd5 [E1-, E2b-, E3-] vector-based targeting vaccine encoding the SARS-CoV-2 S and N proteins. The hAd5-S-Fusion+N-ETSD vaccine is designed to induce both humoral and cellular responses even in individuals with pre-existing adenoviral immunity.<br>|
| Experimental: Cohort 2 (n = 10): hAd5-S-Fusion+N-ETSD at 1 × 10e11 VP per dose<br>hAd5-S-Fusion+N-ETSD at 1 × 10e11 VP per dose on Days 1 and 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* The hAd5-S-Fusion+N-ETSD vaccine is a hAd5 [E1-, E2b-, E3-] vector-based targeting vaccine encoding the SARS-CoV-2 S and N proteins. The hAd5-S-Fusion+N-ETSD vaccine is designed to induce both humoral and cellular responses even in individuals with pre-existing adenoviral immunity.<br>|
| Experimental: Cohort 3 (n = 15): hAd5-S-Fusion+N-ETSD at 1 × 10e11 VP per dose<br>hAd5-S-Fusion+N-ETSD at 1 × 10e11 VP per dose (or 5 × 10e10 VP per dose if safety concerns identified at higher dose) on Days 1 and 22 | Biological: hAd5-S-Fusion+N-ETSD vaccine<br>* The hAd5-S-Fusion+N-ETSD vaccine is a hAd5 [E1-, E2b-, E3-] vector-based targeting vaccine encoding the SARS-CoV-2 S and N proteins. The hAd5-S-Fusion+N-ETSD vaccine is designed to induce both humoral and cellular responses even in individuals with pre-existing adenoviral immunity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 1 week post final vaccine administration | 1 week post final vaccine administration | 
| Incidence and severity of solicited local reactogenicity AEs | Incidence and severity of solicited local reactogenicity AEs through 1 week post final vaccine administration | 1 week post final vaccine administration | 
| Incidence and severity of solicited systemic reactogenicity AEs | Incidence and severity of solicited systemic reactogenicity AEs through 1 week post final vaccine administration | 1 week post final vaccine administration | 
| Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 1 week post final vaccine administration | 1 week post final vaccine administration | 
| Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs through 30 days and 6 months post final vaccine administration | 30 days and 6 months post final vaccine administration | 
| Incidence and severity of unsolicited AEs | Incidence and severity of unsolicited AEs through 30 days and 6 months post final vaccine administration | 30 days and 6 months post final vaccine administration | 
| Incidence of changes of laboratory safety examinations | Incidence of abnormal changes of laboratory safety examinations | Day 387 | 
| Vital Sign - Temperature | Changes in vital signs from Grades 1-4: Temperature - measured in (°C) or (°F) | Day 387 | 
| Vital Sign - Heart rate | Changes in vital signs from Grades 1-4: Heart rate - measured by how many heart beats per minute | Day 387 | 
| Vital Sign - Blood Pressure | Changes in vital signs from Grades 1-4: Systolic/Diastolic - measured in mm Hg | Day 387 | 
| Vital Sign - Respiratory Rate | Changes in vital signs from Grades 1-4: Respiratory Rate - measured in how many breaths per minute | Day 387 | 
| GMFR in IgG titer | GMFR in IgG titer to S, RBD and N , in the absence of evidence of incident natural infection | Day 387 | 
| GMT of S-specific, RBD-specific, and N-specific antibodies | GMT of S-specific, RBD-specific, and N-specific antibodies against 2019 novel coronavirus tested by ELISA in serum , in the absence of evidence of incident natural infection | Day 387 | 
| Percentage of participants who seroconverted | Percentage of participants who seroconverted (as defined as 4-fold change in antibody titer relative to baseline) , in the absence of evidence of incident natural infection | Day 387 | 
| GMFR in neutralizing antibody | GMFR in neutralizing antibody, in the absence of evidence of incident natural infection | Day 387 | 
| GMT of neutralizing antibody | GMT of neutralizing antibody, in the absence of evidence of incident natural infection | Day 387 | 
| Seroconversion rate of neutralizing antibody | Seroconversion rate of neutralizing antibody (as defined as 4-fold change in antibody titer relative to baseline) , in the absence of evidence of incident natural infection | Day 387 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New HIV infections in vaccine recipients | New HIV infections in vaccine recipients by either two, different locally approved rapid antibody tests or by ELISA | 12 months post final vaccine administration |