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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by The Wistar Institute
Sponsor:
Collaborators:
University of Pennsylvania
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Luis Montaner, The Wistar Institute
ClinicalTrials.gov Identifier:
NCT01935089
First received: August 27, 2013
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Pegylated Interferon alpha 2b
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study: Single Arm, Multi-site, Open-label Study to Assess the Effectiveness of Peg-IFN-a2b in Decreasing the Levels of Cell-associated Integrated Viral DNA in HIV Chronic Infection

Resource links provided by NLM:


Further study details as provided by The Wistar Institute:

Primary Outcome Measures:
  • Change from baseline in copies of HIV DNA per CD4+ T cell at Week 24 [ Time Frame: Week 0 and 24 ] [ Designated as safety issue: No ]
    Assessed by Alu-HIVgag polymerase chain reaction


Estimated Enrollment: 25
Study Start Date: November 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Interferon alpha
pegylated Interferon alpha 2b (Pegintron) 1 µg/kg per week, 20 weeks
Drug: Pegylated Interferon alpha 2b
1µg/kg/week
Other Name: Pegintron

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18-65 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))

Exclusion Criteria:

  • 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:

    1. Anemia (Hgb <9.1 mg/dl men, <8.9 mg/dl women)
    2. WBC <2000 cells/µl
    3. Absolute neutrophil count (ANC) <1200 cells/ µl
    4. Platelet count <60,000 cells/ µl
    5. 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)
    6. Renal disease (creatinine > 2x upper normal limits or creatinine clearance <60mg/dl (by Crockoff-Gault)
  • Chronic HCV infection (HCV viremia), or HBV Ag positive and/ or HBV viremia (Notice: subjects with prior HCV infection with a documented sustained virologic response with treatment finishing >1 year prior to screening are eligible for enrollment).
  • Liver cirrhosis or hepatic decompensation with Child Pugh score > 6
  • History of major organ transplantation with an existing functional graft.
  • Evidence of OI or other active infectious diseases or active malignancies
  • Active Autoimmune diseases, including autoimmune hepatitis
  • History of retinopathy or clinically significant ophthalmologic disease on eye exam performed within 6 months prior to initiation of IFN
  • Pregnancy, actively attempting to become pregnant, or breastfeeding
  • Body weight under 125 lbs or over 300 lbs
  • Other conditions, such as active drug/alcohol abuse or dependence which would interfere with study compliance
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01935089

Contacts
Contact: Luis J Montaner, DPhil 215-898-3934 montaner@wistar.org
Contact: Jay R Kostman, MD 215-662-8693 kostman@mail.med.upenn.edu

Locations
United States, Pennsylvania
AIDS Clinical Trials Unit (ACTU), and Department of Medicine, University of Pennsylvania Perelman School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Pablo Tebas, MD    215-615-4321    pablo.tebas@uphs.upenn.edu   
Contact: Kathryn Maffei, RN    215-349-8092    kathryn.maffei@uphs.upenn.edu   
Principal Investigator: Pablo Tebas, MD         
Jonathan Lax Clinic, Philadelphia FIGHT Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Karam Mounzer, MD    215-985-4448 ext 139    mounzerk@fight.org   
Contact: Angela Kapalko    215-985-4448 ext 126    akapalko@fight.org   
Principal Investigator: Karam Mounzer, MD         
Presbyterian Hospital, Department of Medicine, University of Pennsylvania Perelman School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jay R Kostman, MD    215-662-8693    kostman@mail.med.upenn.edu   
Contact: Kenneth Lynn, RN    215-662-8217    Kenneth.Lynn@uphs.upenn.edu   
Principal Investigator: Jay R Kostman, MD         
Sponsors and Collaborators
The Wistar Institute
University of Pennsylvania
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Luis J Montaner, DPhil University of Pennsylvania
  More Information

No publications provided

Responsible Party: Luis Montaner, Professor, The Wistar Institute
ClinicalTrials.gov Identifier: NCT01935089     History of Changes
Other Study ID Numbers: Merck-0575
Study First Received: August 27, 2013
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by The Wistar Institute:
HIV-1
Interferon alpha
Integrated DNA
Latent reservoir

Additional relevant MeSH terms:
Communicable Diseases
Infection
Interferon-alpha
Interferons
Peginterferon alfa-2b
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014