Evaluation of Safety, Immunogenicity and Efficacy of a Triple Immune Regimen in Adults Initiated on ART During Acute HIV-1
A Phase I/IIa Randomized, Placebo-Controlled Trial of Conserved-Mosaic T-cell Vaccine in a Regimen With Vesatolimod and Broadly Neutralizing Antibodies in Adults Initiated on Suppressive Antiretroviral Therapy During Acute HIV-1
National Institute of Allergy and Infectious Diseases (NIAID)
36 participants
Apr 1, 2024
INTERVENTIONAL
Conditions
Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of therapeutic vaccination with chimpanzee adenovirus ChAdOx1- and poxvirus modified vaccinia Ankara (MVA)-vectored conserved mosaic T-cell vaccines in a sequential regimen with the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) and two broadly neutralizing antibodies (bNAbs) compared to placebo, to induce HIV-1 control during analytic treatment interruption (ATI).
Eligibility
Inclusion Criteria14
- Provision of written informed consent.
- History of Initiation of combination ART within 90 days of acute HIV diagnosis
- On ART for at least 12 months with no known ART interruption \>28 consecutive days within 12 months prior to Step 1 Study Entry
- ART with an integrase inhibitor-based regimen with two NRTIs or dolutegravir/lamivudine regimen for at least 6 weeks prior to Study Entry.
- Willingness to participate in the ATI and willingness to restart ART according to study guidelines.
- Willingness to adhere to protocol therapy and complete all study visits.
- Weight ≥50 kg and ≤150 kg at Screening.
- CD4 cell count ≥500 cells/mm3 obtained within 60 days prior to Study Entry.
- HIV-1 RNA \<50 copies/mL (or below the assay limit of quantification if local assay lower limit of quantification is \>50 copies/mL) for at least 1 year and within 60 days prior to Study Entry.
- Select laboratory results within 60 days of study entry
- For cisgender women and transgender men of reproductive potential, negative urine or serum pregnancy test within 48 hours prior to or at study Entry.
- Participants who are able to become pregnant and who are engaging in sexual activity that could lead to pregnancy must agree to use two methods of contraception, one of which must be a highly effective methods for contraception. Barrier methods of contraception are required for the second method of contraception.
- Availability of results of HLA typing (required for randomization).
- Completion of pre-entry leukapheresis or LVBD.
Exclusion Criteria27
- Currently pregnant or breastfeeding or planning to become pregnant during study participation.
- Prior receipt of anti-HIV broadly neutralizing antibody therapy.
- Receipt of any non-HIV monoclonal antibody therapy within 1 year prior to study entry.
- Prior receipt of a latency-reversing agent (LRA).
- Receipt of HIV-1 or other investigational vaccines within 6 months prior to Study Entry.
- Receipt of a live-virus vaccine within 60 days or any vaccination within 14 days prior to Study Entry.
- Receipt of any simian adenovirus-vectored vaccine (e.g., anti-COVID-19 AZD1222) within 12 months prior to Step 1 Study Entry.
- Known allergy/sensitivity or any hypersensitivity to components of study treatments or their formulations.
- Known severe chicken egg allergy.
- Known history of a severe reaction or anaphylaxis to prior vaccinations or antibody preparations (e.g., intravenous immunoglobulin).
- Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity).
- Any history of anaphylaxis and related symptoms such as hives, respiratory difficulty, or angioedema.
- Previous or current history of bleeding factor deficiency, coagulopathy or platelet disorder or on chronic anticoagulation.
- History of inflammatory neurologic diseases.
- History of pregnancy, head trauma or major surgery within 90 days prior to Step 1 Study Entry.
- History of use of any immunomodulatory medications within the 6 months prior to Step 1 Study Entry.
- Significant serious skin disease, such as but not limited to active rash, eczema, psoriasis, or urticaria.
- Autoimmune disease (e.g., lupus, multiple sclerosis, and others) requiring ongoing immunosuppression.
- Known history of CDC Stage 3 opportunistic infection (OI).
- Any history of an HIV-associated malignancy.
- Known or suspected active or untreated latent Mycobacterium tuberculosis infection.
- Active or recent non-HIV-associated malignancy.
- Serious illness requiring systemic treatment and/or hospitalization within 90 days prior to study entry.
- Known resistance to one or more drugs in two or more ARV drug classes.
- History of or current clinical atherosclerotic cardiovascular disease
- Current advanced liver disease.
- Use of complementary or alternative medicines within 14 days prior study entry.
Interventions
Administered as 0.4 mL intramuscularly (IM) at Week 0
Administered as 0.3 mL IM at Week 0
Administered as 0.3 mL IM at Week 4
Administered as 0.5 mL IM at week 4
VES 6 mg administered orally once every 2 weeks for two doses, then VES 8 mg once every 2 weeks for 8 doses. Dose escalation may be held or the 8 mg dose may be reduced for intolerability for weeks 6 through 24.
Administered via intravenous (IV) infusion at week 7
Administered via IV infusion at week 7
Administered 0.5 mL IM at week 60
Placebos for vaccines, VES, and bnAbs
Locations(12)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06071767