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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01935089
• Other study ID #: Merck-0575
• Status: Completed
• Phase: Phase 2
• Start date: August 7, 2013
• Est. completion date: May 2, 2016

Study information

• Verified date: July 2023
• Source: The Wistar Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2, 2016
• Est. primary completion date: March 25, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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-a2b, 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

Related Conditions & MeSH terms

• HIV-1 Infection
• Infections

Intervention

Drug:
• Pegylated Interferon alpha 2b
1µg/kg/week

Locations

Country	Name	City	State
United States	AIDS Clinical Trials Unit (ACTU), and Department of Medicine, University of Pennsylvania Perelman School of Medicine	Philadelphia	Pennsylvania
United States	Jonathan Lax Clinic, Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	Presbyterian Hospital, Department of Medicine, University of Pennsylvania Perelman School of Medicine	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
The Wistar Institute	Merck Sharp & Dohme LLC, University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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