Pilot Peg-Interferon-a2b in Decreasing Viral DNA in HIV
This trial is active, not recruiting.
|Treatment||pegylated interferon alpha 2b|
|Sponsor||The Wistar Institute|
|Collaborator||University of Pennsylvania|
|Start date||November 2013|
|End date||July 2017|
|Trial size||25 participants|
|Trial identifier||NCT01935089, 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.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Philadelphia, PA||AIDS Clinical Trials Unit (ACTU), and Department of Medicine, University of Pennsylvania Perelman School of Medicine||no longer recruiting|
|Philadelphia, PA||Presbyterian Hospital, Department of Medicine, University of Pennsylvania Perelman School of Medicine||no longer recruiting|
|Philadelphia, PA||Jonathan Lax Clinic, Philadelphia FIGHT||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
pegylated Interferon alpha 2b (Pegintron) 1 µg/kg per week, 20 weeks
Change from baseline in copies of HIV DNA per CD4+ T cell at Week 24
time frame: Week 0 and 24
Male or female participants from 18 years up to 65 years old.
- 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))
- 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)
- 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
|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|
|Principal investigator||Luis J Montaner, DPhil|
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