Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy

NCT02471430 | Completed Phase 1 Results DMC

• 2 other identifiers: U01 2015P00085812049
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (2)

• Occurrence of Grade ≥ 1 Adverse Events (AEs)

  Cumulative frequency and severity of Grade ≥ 1 adverse events, Grade ≥ 1 lab abnormalities or serious adverse events

  All adverse events measured from day 1 until day 28 after administration of the first dose of panobinostat and/or interferon-alpha2a was recorded.

• Change in CD4 T Cell-Associated Proviral HIV-1 DNA From Baseline

  Operational measurement of CD4 T cells harboring genome-intact HIV-1 DNA, determined by the IPDA assay.

  Measured through week 4 after administration of panobinostat and/or interferon-alpha2a

Secondary Outcomes (3)

• Change From Baseline in Histone H3 Acetylation in CD4 T Cells

  measured after last dose of PBT on day 4

• Change From Baseline in Levels of CD4 T Cell-associated HIV-1 RNA

  measured after last dose of PBT on day 4

• Change From Baseline in Frequency of Activated NKp30+ NK Cells.

  measured after last dose of PBT on day 4

Study Arms (3)

Arm A

EXPERIMENTAL

Participants in Arm A will receive panobinostat as an oral tablet on days 0, 2, and 4 of the treatment week. The dose of panobinostat will be a 15 mg tablet.

Drug: Panobinostat

Arm B

EXPERIMENTAL

Participants in Arm B will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0. The dose of pegylated IFN-alpha2a will be 180 mcg. Simultaneously with interferon-alpha2a, a 15 mg tablet of panobinostat will be administered on day 0. Participants will also receive panobinostat as an oral tablet on days 2 and 4 of the treatment week.

Drug: Panobinostat; Drug: Pegylated Interferon-alpha2a

Arm C

EXPERIMENTAL

Participants in Arm C will receive one subcutaneous injection of pegylated interferon-alpha2a on day 0.The dose of pegylated IFN-alpha2a will be 180 mcg.

Drug: Pegylated Interferon-alpha2a

Interventions

Panobinostat DRUG

Panobinostat will be administered orally.

Also known as: Farydak, LBH589

Arm A; Arm B

Pegylated Interferon-alpha2a DRUG

Pegylated Interferon-alpha2a will be administered subcutaneously in one shot.

Also known as: Pegasys

Arm B; Arm C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• CD4 T cell count ≥ 400 cells/mm3
• Negative Hepatitis B surface antigen (HBsAg) or Negative HBV DNA PCR
• Negative anti-Hepatitis C virus antibodies (anti-HCV) or negative HCV PCR if anti-HCV antibodies are positive
• Negative TB Test (if positive, completed a recommended treatment course for latent TB)
• Vaccinated for pneumococcal disease within last 5 years
• No clinically significant eye disease
• No evidence of clinical coronary heart disease
• Not pregnant, planning to become pregnant, or breastfeeding
• Willingness to continue to use contraceptives for 90 days after completing treatment
• If male, willingness to use a condom during intercourse while taking panobinostat and total of 80 hours after stopping treatment
• Not pregnant, planning to become pregnant, or breastfeeding

You may not qualify if:

• HIV-1 RNA \> 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Novartis: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Rasmussen TA, Tolstrup M, Brinkmann CR, Olesen R, Erikstrup C, Solomon A, Winckelmann A, Palmer S, Dinarello C, Buzon M, Lichterfeld M, Lewin SR, Ostergaard L, Sogaard OS. Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV. 2014 Oct;1(1):e13-21. doi: 10.1016/S2352-3018(14)70014-1. Epub 2014 Sep 15.

  PMID: 26423811 BACKGROUND

MeSH Terms

Conditions

HIV Infections

Interventions

Panobinostat; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mathias Lichterfeld
• Organization: Massachusetts General Hospital

mlichterfeld@mgh.harvard.edu

617-726-2000

Study Officials

• Mathias Lichterfeld, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Daniel R Kuritzkes, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Rajesh T Gandhi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 11, 2015
• First Posted: June 15, 2015
• Study Start: May 1, 2016
• Primary Completion: August 1, 2022
• Study Completion: December 1, 2023
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-02

Locations

US (1)