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

Merck-0575

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.

2013-08-07

2015-03-25

2016-05-02

Completed

Early phase I

20

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ACTUAL'}}

2023-07-06