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

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Biological: AAHI-SC2 Vaccine; Biological: AAHI-SC3 Vaccine; Biological: EUA or approved vaccine

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Africa
  • Johannesburg, South Africa
    • Wits Vida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy adults ≥ 18 years of age at time of enrollment.
2. 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.
3. Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
4. Agrees to the collection of biospecimens (eg, nasopharyngeal [NP] swabs) and venous blood per protocol.
5. Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
6. Temperature < 38°C.
7. 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.
8. 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:

1. 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.
2. Confirmed current COVID-19, previous SARS-CoV-2 infection in the last < 3 months, or PCR positive for SARS-CoV-2 at screening.
3. Vaccinated with an EAU-approved vaccine against COVID-19 in the last < 3 months.
4. Pregnant or breastfeeding women.
5. 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.
6. Bone marrow or organ transplant recipient
7. Extreme obesity (defined as BMI of 40 kg/m2 or higher).
8. Chronic kidney disease requiring dialysis.
9. History of liver disease.
10. Any disease associated with acute fever, or any infection.
11. Participants with acquired or hereditary immunodeficiencies other than well-controlled HIV are excluded from enrollment.
12. Current diagnosis of active tuberculosis.
13. History of hereditary, idiopathic or acquired angioedema.
14. No spleen or functional asplenia.
15. 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.
16. 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.
17. Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

10

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Safety - Incidence of MAAEs Through 1 Week	Incidence of medically-attended adverse events (MAAEs)	through 1 week post final vaccine administration
Phase 1 Safety - Incidence of MAAEs Through 30 Days	Incidence of MAAEs	through 30 days post final vaccine administration
Phase 1 Safety - Incidence of MAAEs Through 6 Months	Incidence of MAAEs	through 6 months post final vaccine administration
Phase 1 Safety - Incidence of Solicited 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 SAEs Through 1 Week	Incidence of serious adverse events (SAEs)	through 1 week post final vaccine administration
Phase 1 Safety - Incidence of SAEs Through 30 Days	Incidence of SAEs	through 30 days post final vaccine administration
Phase 1 Safety - Incidence of SAEs Through 6 Months	Incidence of SAEs	through 6 months post final vaccine administration

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

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2022
• Primary Completion (Actual): March 11, 2024
• Study Completion (Actual): March 11, 2024

Study Registration Dates

• First Submitted: May 9, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: COVID-4.015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes