THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines

Study Overview
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Brief Summary
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This is a phase 1/2 open-label study assessing the safety, reactogenicity, and immunogenicity of saRNA COVID-19 boost vaccines in participants that have been previously vaccinated against or previously infected with COVID-19.

Official Title
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THEMBA II T-CELL Vaccine: A Phase 1/2 Study of the Safety, Reactogenicity, and Immunogenicity of Vaccination With saRNA COVID-19 Vaccines

Conditions
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COVID-19

Intervention / Treatment
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* Biological: AAHI-SC2 Vaccine
* Biological: AAHI-SC3 Vaccine
* Biological: EUA or approved vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults ≥ 18 years of age at time of enrollment. Vaccinated with an EUA or approved vaccine against COVID-19 ≥ 3 months prior to enrollment on study or infection with COVID-19 ≥ 3 months prior to enrollment on study. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines. Agrees to the collection of biospecimens (eg, 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. Temperature < 38°C. Agreement to practice effective contraception for female participants of childbearing potential and non-sterile males. Female participants of childbearing potential must agree to use effective contraception while on study until at least 1 month after the last dose of vaccine. Non-sterile male participants must agree to use a condom while on study until at least 1 month after the last dose of vaccine. Effective contraception includes surgical sterilization (eg, vasectomy, tubal ligation), two forms of barrier methods (eg, condom, diaphragm), intrauterine devices (IUDs), oral contraceptives, injectable contraceptives, patches, implants and abstinence. HIV-positive participants must have been on anti-retroviral therapy for ≥ 4 weeks and have HIV-1 viral load < 1,000 copies/mL at the time of enrollment. Exclusion Criteria: 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. Confirmed current COVID-19, previous SARS-CoV-2 infection in the last < 3 months, or PCR positive for SARS-CoV-2 at screening. Vaccinated with an EAU-approved vaccine against COVID-19 in the last < 3 months. Pregnant or breastfeeding women. Chronic lung disease (included COPD) as evidenced by one or more exacerbations requiring a course of steroids in the last year, or the requiring chronic low dose oral steroids to prevent exacerbations. Uncontrolled asthma, defined as requiring reliever inhaler (short-acting beta agonist or ipratromium bromide) more than twice a week is also excluded. Bone marrow or organ transplant recipient Extreme obesity (defined as BMI of 40 kg/m2 or higher). Chronic kidney disease requiring dialysis. History of liver disease. Any disease associated with acute fever, or any infection. Participants with acquired or hereditary immunodeficiencies other than well-controlled HIV are excluded from enrollment. Current diagnosis of active tuberculosis. History of hereditary, idiopathic or acquired angioedema. No spleen or functional asplenia. 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, or immunomodulators. The use of low dose topical, ophthalmic, inhaled and intranasal steroid preparations will be permitted. According to the judgement of the 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: 55 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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Open label 6 Cohort Phase 1 Study leading to Randomized 4 Cohort Phase 2 Study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Cohort 1A<br>AAHI-SC2 on Day 1 at dosage 25 μg IM | Biological: AAHI-SC2 Vaccine<br>* AAHI -SC2 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 1 Cohort 1B<br>AAHI-SC2 on Day 1 at dosage 50 μg IM | Biological: AAHI-SC2 Vaccine<br>* AAHI -SC2 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 1 Cohort 1C<br>AAHI-SC2 on Day 1 at dosage 70 μg IM | Biological: AAHI-SC2 Vaccine<br>* AAHI -SC2 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 1 Cohort 2A<br>AAHI-SC3 on Day 1 at dosage 25 μg IM | Biological: AAHI-SC3 Vaccine<br>* AAHI-SC3 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike and nucleocapsid protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 1 Cohort 2B<br>AAHI-SC3 on Day 1 at dosage 50 μg IM | Biological: AAHI-SC3 Vaccine<br>* AAHI-SC3 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike and nucleocapsid protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 1 Cohort 2C<br>AAHI-SC3 on Day 1 at dosage 85 μg IM | Biological: AAHI-SC3 Vaccine<br>* AAHI-SC3 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike and nucleocapsid protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Placebo Comparator: Phase 2 Control arm<br>EUA or approved vaccine on Day 1 | Biological: EUA or approved vaccine<br>* Janssen or Pfizer vaccines (control arm)<br>|
| Experimental: Phase 2 Experimental arm 1<br>AAHI-SC2 on Day 1 Dose TBD as determined in phase 1 study | Biological: AAHI-SC2 Vaccine<br>* AAHI -SC2 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 2 Experimental arm 2<br>AAHI-SC3 on Day 1 Dose TBD as determined in phase 1 study | Biological: AAHI-SC3 Vaccine<br>* AAHI-SC3 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike and nucleocapsid protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|
| Experimental: Phase 2 Experimental arm 3<br>AAHI-SC3 on Day 1 and 29 Dose TBD as determined in phase 1 study | Biological: AAHI-SC3 Vaccine<br>* AAHI-SC3 self-amplifying RNA (saRNA) against SARS-CoV-2 Spike and nucleocapsid protein delivered by nanostructured lipid carrier (NLC) Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Safety - Incidence of medically-attended MAAEs and SAEs | Incidence of medically-attended adverse events (MAAEs) and serious adverse events (SAEs) | through 1 week post final vaccine administration | 
| Phase 1 Safety - Incidence of MAAEs and SAEs through 30 days | Incidence of MAAEs and SAEs | through 30 days post final vaccine administration | 
| Phase 1 Safety - Incidence of MAAEs and SAEs through 6 months | Incidence of MAAEs and SAEs | through 6 months post final vaccine administration | 
| Phase 1 Safety - Incidence of local reactogenicity AEs | Incidence and severity of solicited local reactogenicity AEs | through 1 week after each vaccine dose | 
| Phase 1 Safety - Incidence of solicited systemic reactogenicity AEs | Incidence and severity of solicited systemic reactogenicity AEs | through 1 week after each vaccine dose | 
| Phase 1 Safety - Incidence of unsolicited AEs through 1 week | Incidence and severity of unsolicited AEs | through 1 week post final vaccine administration | 
| Phase 1 Safety - Incidence of unsolicited AEs through 30 days | Incidence and severity of unsolicited AEs | through 30 days post final vaccine administration | 
| Phase 1 Safety - Incidence of abnormal changes of laboratory safety examinations | Incidence of abnormal changes of laboratory safety examinations | Day 365 | 
| Phase 1 Safety - Vital Sign - Temperature | Changes in vital signs from Grades 1-4: measured in (°C) or (°F) | Day 365 | 
| Phase 1 Safety - Vital Sign - Heart Rate | Changes in vital signs from Grades 1-4: measured by how many heart beats per minute | Day 365 | 
| Phase 1 Safety - Vital Sign - Blood Pressure | Changes in vital signs from Grades 1-4: systolic/diastolic - measured in mm Hg | Day 365 | 
| Phase 1 Safety - Vital Sign - Respiratory Rate | Changes in vital signs from Grades 1-4: measured in how many breaths per minute | Day 365 | 
| Phase 2 Humoral Immunogenicity - GMT of S-specific and N-specific IgG antibodies | GMT of S-specific and N-specific IgG antibodies against 2019 novel coronavirus tested by ELISA in serum | Day 365 | 
| Phase 2 Humoral Immunogenicity - GMT of neutralizing antibody | GMT of neutralizing antibody | Day 365 | 
| Phase 2 Cellular Immunogenicity - T cell activity | T cell activity against SARS-CoV-2 S protein and N protein as assayed by the ELISpot assay | Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Humoral Immunogenicity - GMT of S-specific and N-specific IgG antibodies | Geometric mean titer (GMT) of S-specific and N-specific IgG antibodies against 2019 novel coronavirus tested by ELISA in serum | Day 365 | 
| Phase 1 Humoral Immunogenicity - GMT of neutralizing antibody | GMT of neutralizing antibody | Day 365 | 
| Phase 1 Cellular Immunogenicity - T cell activity | T cell activity against SARS-CoV-2 S protein and N protein as assayed by ELISpot | Day 365 | 
| Phase 2 Safety - Incidence of MAAEs and SAEs | Incidence of MAAEs and SAEs | through 30 days post final vaccine administration | 
| Phase 2 Safety - Incidence of Incidence of MAAEs and SAEs through 6 months | Incidence of MAAEs and SAEs | through 6 months post final vaccine administration | 
| Phase 2 Safety - Incidence of solicited local reactogenicity AEs | Incidence and severity of solicited local reactogenicity AEs | through 1 week after each vaccine dose | 
| Phase 2 Safety - Incidence of solicited systemic reactogenicity AEs | Incidence and severity of solicited systemic reactogenicity AEs | through 1 week after each vaccine dose | 
| Phase 2 Safety - Incidence of unsolicited AEs | Incidence and severity of unsolicited AEs | through 30 days post final vaccine administration |