Phase 2
N=17
Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy
HIV Infection
Bottom Line
View on ClinicalTrials.gov: NCT02471430 ↗Enrolled (actual)
17
Serious AEs
0.0%
Results posted
Feb 2024
Primary outcome: Primary: Occurrence of Grade ≥ 1 Adverse Events (AEs) — 5; 26; 4 events
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Panobinostat (Drug); Pegylated Interferon-alpha2a (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Massachusetts General Hospital
- Primary completion
- Aug 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Occurrence of Grade ≥ 1 Adverse Events (AEs) |
5; 26; 4 | — |
| PRIMARY Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline |
32.6; 179; 24; 44.7; 108.4; 18.7 | — |
| SECONDARY Change From Baseline in Histone H3 Acetylation in CD4 T Cells |
2; 3.1; 5.5; 23.2; 14.7; 8.3 | — |
| SECONDARY Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA |
1055.6; 630.6; 772.5; 1611.2; 1138.4; 958.8 | — |
| SECONDARY Change From Baseline in Frequency of Activated NKp30+ NK Cells. |
22.8; 30.9; 21.4; 23; 37.8; 25.5 | — |
Summary
This study is a prospective, open-label, randomized, three-arm, dose-escalation exploratory pilot clinical trial involving HIV-1 infected participants treated with suppressive combination antiretroviral combination therapy (cART). The study will test whether combined treatment with the histone deacetylase inhibitor panobinostat and the immunomodulatory cytokine Interferon-alpha2a can reduce the residual reservoir of HIV-1 infected cells that persist during treatment with currently available antiretroviral drugs.
Eligibility Criteria
Inclusion Criteria
- Ability and willingness to provide informed consent
- HIV-1 infection prior to entry
- Receiving suppressive ART therapy for a minimum of 24 consecutive months prior to screening with no interruption of therapy (same ART regimen for at least 12 weeks prior to screening)
- Documented suppressed HIV-1 RNA (plasma HIV-1 RNA values 50 copies/mL within 24 months of screening
- Severe psychiatric disease, chronic liver disease, past or current evidence of immunologically mediated disease
- Severe retinopathy due to diabetes, hypertension, cytomegalovirus or macular degeneration
- Evidence of coronary heart disease
- History of active thyroid disease requiring medication
- Breastfeeding
- Presence of a bacterial, fungal, viral or protozoal infection requiring systemic anti-infective therapy
- Uncontrolled seizure disorders
- History or other evidence of severe illness or other conditions
- History of malignancy of any organ system within the past 5 years
- Female participants who are pregnant or nursing
- History of solid organ transplantation with an existing functional graft
- Use of any immunomodulatory agents within 30 days prior to study enrollment or planned use during the trial
- Active drug or alcohol use or dependence
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in case of participation in the study
- Use of HIV protease inhibitor or other strong or moderately strong CYP3A4 inhibitors
- History of anaphylaxis, allergy or serious adverse reactions to Interferon-alpha2a/Interferon-alpha2b or panobinostat
- Has taken: interleukins, systemic interferons or systemic chemotherapy
Data sourced from ClinicalTrials.gov (NCT02471430). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.