Clinical trial NCT01935089: Pilot Peg-Interferon-a2b in Decreasing Viral DNA in HIV
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Keywords: HIV-1
Interferon alpha
Integrated DNA
Latent reservoir
Lead sponsor: The Wistar Institute
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: Merck Sharp & Dohme LLC
First posted: 2013-09-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline in Copies of HIV DNA Per CD4+ T Cell at Week 24
timeFrame: Week 3 and 24
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: AIDS Clinical Trials Unit (ACTU), and Department of Medicine, University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Presbyterian Hospital, Department of Medicine, University of Pennsylvania Perelman School of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jonathan Lax Clinic, Philadelphia FIGHT
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Luis J Montaner, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.