Pilot Peg-Interferon-a2b in Decreasing Viral DNA in HIV

NCT01935089 | Completed Phase 2 Results DMC

• 1 other identifier: Merck-0575
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

We propose to test our primary hypothesis that treatment with Peg-IFN-α-2b will result in a decrease in integrated HIV DNA in peripheral blood and tissue in chronically HIV-infected immune-reconstituted individuals (see section 3.1) in a prospective, interventional, 1-arm, open label clinical trial. To this end, we propose to enroll 25 HIV-1-infected subjects (please refer to power calculations in section 10.1 below) currently stably suppressed (\> 1y with VL \< 50 copies/ml) on ART and with CD4 count \> 450 cells/µl. We hypothesize that 20 weeks of treatment with Peg-IFN-alpha-2b, in the presence of HIV reactivation (i.e.: ART interruption), will result in activation of intrinsic and/or immune-mediated anti-HIV mechanisms resulting in a decrease in the levels of viral reservoir in chronically HIV-infected, immune-reconstituted individuals.

Conditions

HIV-1 Infection

Keywords

HIV-1; Interferon alpha; Integrated DNA; Latent reservoir

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24

  Difference in copies of HIV DNA per CD4+ T cell between baseline and week 24, assessed by Alu-HIVgag polymerase chain reaction

  Week 3 and 24

Study Arms (1)

Interferon alpha

EXPERIMENTAL

pegylated Interferon alpha 2b (Pegintron) 1 µg/kg per week, 20 weeks

Drug: Pegylated Interferon alpha 2b

Interventions

Pegylated Interferon alpha 2b DRUG

1µg/kg/week

Also known as: Pegintron

Interferon alpha

Eligibility Criteria

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

You may qualify if:

• years of age
• Body weight between 125 and 299 lbs
• Confirmed diagnosis of HIV-1 infection by western blot or by a documented HIV-1 viral load
• Currently receiving ART and on ART for \> 1 year
• VL \< 50 copies/ml for ≥ 1 year, with at least 2 measurements in the previous year, 1 viral "blip" with VL\< 400 copies/ml allowed
• HIV viral load of \<50 copies/ml at screening.
• CD4 \>450 cells/µL at screening.
• A negative ECG if \>45yrs men/\>55yrs women years of age or if below these years of age but with two added risk factors for coronary artery disease \[smoking, hypertension (BP \>140/90 or on antihypertensive medications), low HDL (\<40 mg/dL), family history of premature CHD (\<55 yrs males/\<65 females)\] or a Framingham score \> 15% (men) or 10% (women))

You may not qualify if:

• Confirmed clinical history of developing resistance to ART regimens that resulted in treatment changes
• Receiving didanosine as part of the participant's ART regimen at the time of screening
• Ongoing treatment with Isoniazide, pyrazinamide, Rifabutin, Rifampicin, Diadenosine Ganciclovir, Valgancyclovir, Oxymetholone, Thalidomide or Theophylline.
• Use of any investigational drug within 30 days prior to screening
• History or current use of immunomodulatory therapy for over 2 weeks during the 6 months prior to enrollment, including, but not limited to: IFN-alpha or gamma (recombinant or pegylated), systemic corticosteroids (nasal or pulmonary steroids will be allowed; systemic cancer chemotherapy/irradiation; cyclosporin; tacrolimus (FK-506); OKT-3; any Interleukin, including IL-2; cyclophosphamide; methotrexate; IVIG (gamma globulin); G/M-CSF; hydroxyurea; thalidomide; pentoxifylline; thymopentin; thymosin; dithiocarbonate; polyribonucleotide.
• History of adverse or allergic reactions to any type-1 interferon (e.g. IFN-alpha2a, IFN-α2b, IFN-beta)
• History of severe depression, or ongoing moderate depression determined by PHQ-9 at screening
• Type I diabetes mellitus, or type II diabetes mellitus that is not controlled with oral agents and/or insulin.
• Prior diagnosis of multiple sclerosis or other neurodegenerative disorders
• Significant co-existing lab abnormalities including:
• Anemia (Hgb \<9.1 mg/dl men, \<8.9 mg/dl women)
• WBC \<2000 cells/µl
• Absolute neutrophil count (ANC) \<1200 cells/ µl
• Platelet count \<60,000 cells/ µl
• Liver disease (AST/ALT \> 2.5x, Total Bilirubin \> 1.5x upper limits of norm (ULN), or Total Bilirubin \>3x ULN if receiving indinavir OR Atazanavir)

Sponsors & Collaborators

• The Wistar Institute: lead
• University of Pennsylvania: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

AIDS Clinical Trials Unit (ACTU), and Department of Medicine, University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Presbyterian Hospital, Department of Medicine, University of Pennsylvania Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Jonathan Lax Clinic, Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (2)

• Papasavvas E, Azzoni L, Ross BN, Fair M, Howell BJ, Hazuda DJ, Mounzer K, Kostman JR, Tebas P, Montaner LJ. Comparable HIV suppression by pegylated-IFN-alpha2a or pegylated-IFN-alpha2b during a 4-week analytical treatment interruption. AIDS. 2021 Oct 1;35(12):2051-2054. doi: 10.1097/QAD.0000000000002961.

  PMID: 34049356 DERIVED

• Papasavvas E, Azzoni L, Pagliuzza A, Abdel-Mohsen M, Ross BN, Fair M, Howell BJ, Hazuda DJ, Chomont N, Li Q, Mounzer K, Kostman JR, Tebas P, Montaner LJ. Safety, Immune, and Antiviral Effects of Pegylated Interferon Alpha 2b Administration in Antiretroviral Therapy-Suppressed Individuals: Results of Pilot Clinical Trial. AIDS Res Hum Retroviruses. 2021 Jun;37(6):433-443. doi: 10.1089/AID.2020.0243. Epub 2021 Jan 29.

  PMID: 33323024 DERIVED

MeSH Terms

Interventions

peginterferon alfa-2b

Results Point of Contact

• Title: Luis J. Montaner
• Organization: The Wistar Institute

montaner@wistar.org

+1 (215) 898-9143

Study Officials

• Luis J Montaner, DPhil

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: September 4, 2013
• Study Start: August 7, 2013
• Primary Completion: March 25, 2015
• Study Completion: May 2, 2016
• Last Updated: July 6, 2023
• Results First Posted: July 6, 2023

Record last verified: 2023-07

Locations

US (3)