Gorilla adenovirus (GRAdHIVNE1) vaccine for adults with and without HIV

A Phase 1 Randomized Double Blinded Placebo Controlled, Dose Ranging Trial, of a Gorilla Adenovirus Vectored Networked Epitopes Vaccine, Administered to Healthy Adults Living Without HIV and Living With HIV, in Southern Africa

This Phase 1 test checks if the GRAdHIVNE1 gorilla adenovirus vaccine is safe and can trigger T-cell immune responses in adults with and without HIV in Southern Africa.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: International AIDS Vaccine Initiative (Research network)
• Drugs / interventions: cART
• Locations: 3 sites (Mtubatuba, KwaZulu-Natal and 2 other locations)
• Trial ID: NCT06617091 on ClinicalTrials.gov

What this trial studies

This Phase 1, randomized, double-blind, placebo-controlled, dose-ranging trial enrolls healthy adults both living with HIV and without HIV at sites in Southern Africa. Participants receive one of several doses of the GRAdHIVNE1 vaccine or placebo and are followed for safety, tolerability, and immunogenicity, with a focus on broad, polyfunctional CD8+ T-cell responses. The design builds on prior T-cell vaccine trials and non-human primate data that identified robust CD8+ responses as important for viral control. Safety and immune data from both HIV-negative and HIV-positive cohorts will guide further preventive and therapeutic vaccine development.

Who should consider this trial

Good fit: Adults 18–50 years old who can comply with study procedures and attend visits at the Southern African sites, including both clinically stable people living with HIV and people without HIV, are eligible.

Not a fit: People outside the 18–50 age range, pregnant individuals, those with uncontrolled HIV or major medical conditions, or those unable to attend follow-up visits are unlikely to receive benefit from participation.

Why it matters

Potential benefit: If successful, the vaccine could induce broad CD8+ T-cell responses that help reduce risk of HIV infection or improve immune control of the virus in people living with HIV.

How similar studies have performed: Previous adenovirus‑vectored HIV vaccine trials have shown acceptable safety and induced immune responses but have not achieved durable viral suppression or clear prevention efficacy, so the approach has supporting signals but remains unproven.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age on the day of screening and has not reached his or her 51st birthday on the day of signing the Informed Consent Document.
2. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
3. In the opinion of the Principal Investigator or designee and based on Assessment of Informed Consent Understanding results, has understood the information provided and potential impact and/or risks linked to administration of the investigational product; written informed consent will be obtained from the participant before any study-related procedures are performed.
4. All sexually active female participants capable of becoming pregnant must commit to use an effective method of contraception from 21 days prior to receiving the IP until 4 months following the last IP administration, including:

   1. Intrauterine device, or contraceptive implant
   2. Hormonal contraception
   3. Successful vasectomy in the male partner (considered successful if a woman reports that a male partner has \[1\] documentation of azoospermia by microscopy (\< 1 year ago), or \[2\] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post-vasectomy)
5. Women who have undergone a hysterectomy, bilateral oophorectomy, or tubal ligation, as well as those who are postmenopausal (\> 45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone \[FSH\] level \> 40 IU/L) will not be required to use contraceptives.
6. Willing to forgo donations of blood, or any other tissues during the study.

   Additional Inclusion criteria for PLWH
7. Confirmed HIV infection (HIV Ab+ or HIV RNA+) by documentation in the medical records or in-clinic HIV testing on screening visit.
8. CD4 ≥ 500 cells/µl at screening.
9. Currently on ART, and documentation of continuous combination ART (cART) for at least 12 months with suppression of plasma HIV-1 viral load \< 50 copies / ml for greater than 6 months prior to trial entry, measured on at least 2 independent occasions that can include the screening viral load. cART is defined as a regimen including ≥ 2 compounds, e.g., 2 nucleoside reverse transcriptase inhibitors plus either non-nucleoside reverse transcriptase inhibitor or protease inhibitor or integrase inhibitor.
10. Viral load \< 50 copies / ml at time of screening (within 28 days prior to IP administration).
11. Must commit to adhering to a suppressive ART regimen for the duration of the study

Exclusion Criteria:

1. Any clinically significant acute or chronic medical condition, other than HIV infection (in Part B only), that is considered progressive or in the opinion of the investigator makes the participant unsuitable for participation in the study.
2. For the PLWH (Part B), history of AIDS-defining illness or CD4 \< 200 cells/µl.
3. If female, pregnant, lactating or planning a pregnancy during the period of screening through completion of the study.
4. In the past 6 months a history of alcohol or substance use, judged by the Investigator to potentially interfere with participant study compliance.

Bleeding disorder that was diagnosed by a physician (e.g., Factor deficiency, coagulopathy or platelet disorder that requires special precautions). Note: A participant who states that he or she has easy bruising or bleeding but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible.

6\. History of a splenectomy. 7. Previous receipt of an adenovirus vectored vaccine. 8. Receipt of live attenuated vaccine or other vaccine within the previous 60 days or planned receipt within 180 days after administration of IP. Receipt of blood transfusion or blood derived products within the previous 3 months.

9\. Participation in another clinical trial of an investigational product currently, within the previous 3 months or expected participation during this study.

10\. Prior receipt of an investigational HIV vaccine candidate, monoclonal antibody or polyclonal immunoglobulin (note: receipt of placebo in a previous HIV vaccine or monoclonal antibody trial will not exclude a participant from participation if documentation is available and the Medical Monitor gives approval).

11\. History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulties, angioedema).

12\. Psychiatric condition that compromises safety of the participant and precludes compliance with the protocol. Specifically excluded are persons with history of psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

13\. If, in the opinion of the Principal Investigator or designee, it is not in the best interest of the participant to participate in the trial.

14\. Seizure disorder: a participant who has had a seizure in the last 3 years is excluded. (Not excluded: a participant with a history of seizures who has neither required medications nor had a seizure for 3 years.) 15. Infectious disease: chronic hepatitis B infection (HbsAg positive), current hepatitis C infection (HCV Ab positive and/ or HCV RNA) or treatment for hepatitis C infection in the past year, or active syphilis (RPR confirmed by TPHA).

16\. A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy.

17\. Active, serious infections (other than HIV infection in PLWH) requiring parenteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrollment.

18\. Any abnormal laboratory parameters at screening per protocol. 19. Any clinically relevant abnormality on history or examination including history of immunodeficiency or autoimmune disease, other than HIV among the PLWH; use of systemic corticosteroids, immunosuppressive, anticancer, or other medications considered significant by the investigator within the previous 6 months.

Eligibility Criteria Specific to PLWoH (Part A) People living without HIV(PLWoH) at screening, must be deemed to be at low risk of HIV infection and willing to maintain low-risk behavior for the duration of the trial.

Where this trial is running

Mtubatuba, KwaZulu-Natal and 2 other locations

• Ahri — Mtubatuba, KwaZulu-Natal, South Africa (Recruiting)
• Dthf — Cape Town, Western Cape, South Africa (Recruiting)
• Mutala — Harare, Harare, Zimbabwe (Recruiting)

Study contacts

• Principal investigator: Theodorah Ndzhukule — Desmond Tutu Health Foundation
• Study coordinator: Vincent Muturi-Kioi, MBChB

Conditions HIV; GRAdHIVNE1 Vaccine