A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of Budigalimab and/or ABBV-382 in People Living with HIV on Stable Antiretroviral Therapy Undergoing Analytical Treatment Interruption
Background and Rationale
HIV infection is a chronic condition that remains a major global health problem, with an estimated 38 million people world-wide living with the disease in 2021. Although ART can suppress HIV replication, significantly decreasing AIDS-related mortality and improving the lives of PLWH, these regimens cannot eliminate the HIV DNA integrated in the genome of CD4+ lymphoid and myeloid cells. A high adherence rate to lifelong chronic ART (which is very stigmatizing) is required to maintain viral suppression in plasma and prevent resistance. However, even for ART-treated PLWH with good adherence and suppressed viremia, a state of chronic low-level inflammation persists, which is associated with increased risk of cardiovascular disease, HIV-associated neurocognitive disorder, and other comorbidities. Chronic use of ART is also associated with long-term toxicities.
Therefore, there is a significant unmet need for a regimen with a finite duration of therapy that could lead to sustained immune-mediated viral suppression (sustained ART-free remission for HIV). Removing the need for chronic ART treatment would revolutionize the standard of care for PLWH.
Objectives and Endpoints
The main objectives of this trial are to evaluate efficacy, safety, tolerability, and PK of budigalimab and/or ABBV-382 versus placebo in PLWH on stable ART undergoing ATI.
The primary endpoint is:
- Viral control (viral load < 1000 copies/mL) at Week 24 without ART restart.
The secondary endpoints are:
- Peak viral load (at rebound) prior to re-starting ART
- Time to first rebound to ≥ 1000 copies/mL during ART interruption.
Investigators
Multicenter
Study Sites
Approximately 90 sites in Belgium, Brazil, Canada, Denmark, France, Germany, Italy, Japan, Poland, Puerto Rico, South Africa, Spain, Sweden, United Kingdom, and United States.
Study Population and Number of Participants to be Enrolled
Approximately 140 participants with a confirmed HIV-1 diagnosis who are on stable ART and willing to undergo ATI will be enrolled in this trial.
Investigational Plan
This is a multicenter, Phase 2 proof of concept, randomized, double- blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, and PK of budigalimab and/or ABBV-382 in PLWH who are on stable ART undergoing ATI.
This study will consist of a 35-day screening period, after which eligible participants will be randomized in a 1:1:1:2:2 ratio to placebo, budigalimab 10 mg IV, ABBV-382 1600 mg IV, budigalimab 10 mg IV + ABBV-382 800 mg IV, or budigalimab 10 mg IV + ABBV-382 1600 mg IV. Starting on Day 1, participants will undergo a closely monitored ART interruption planned for 52 weeks or until ART restart criteria are met.
Additional arms may be initiated at the discretion of the sponsor, including, for example, additional monotherapy or combination treatment arms of budigalimab and/or ABBV-382.
Key Eligibility Criteria
PLWH between 18-70 years old, in general good health and on ART for at least 12 months prior to screening and on current ART regimen for at least 8 weeks prior to screening. Participants must not have had prior exposure to long acting antiretrovirals within 24 weeks or within a period defined by 5 half-lives, whichever is longer, prior to randomization and prior to the first dose of study drug. Participants must have negative HIV-2 Ab at screening; plasma HIV-1 RNA below LLOQ at screening and for at least 6 months prior to screening; and CD4+ T cell count ≥ 500 cells/μL at screening and no known evidence of CD4+ T cell count < 500 cells/μL in the last 12 months prior to screening. Participants must have no known history of CD4+ T cell nadir of ≤ 200 cells/μL during chronic HIV infection.
Participants must not have clinically significant medical disorders per investigator’s assessment that might expose the participants to undue risk of harm, confound study outcomes, or prevent the participant from completing the study.
Study Drug and Duration of Treatment
Budigalimab (ABBV-181) in vials for infusion administration; placebo for budigalimab (0.9% sodium chloride).
ABBV-382 in vials for infusion administration; matching placebo for ABBV-382.
Starting on Day 1, participants will be treated with budigalimab or placebo Q2W 4 doses and ABBV-382 or placebo Q4W 3 doses, for a total duration of study treatment of 8 weeks.
The total study duration will be approximately 57 weeks (inclusive of the Screening Period).
Date of Protocol Synopsis
09 August 2023
