NCT02227277

Brief Summary

The purpose of this study is to determine if treatment with pegylated interferon alpha 2b (peg-IFN-α2b) will reduce the amount of integrated HIV DNA in peripheral blood cells and tissues of individuals with chronic HIV infection receiving antiretroviral treatment (ART). A reduction and/or clearance of the latent viral reservoir (i.e.: virus that remains dormant in HIV-infected subjects receiving suppressive treatment ) is considered essential for HIV eradication. By measuring the changes in integrated proviral HIV DNA, which is considered a surrogate measure of the latent reservoir, the investigators will establish if peg-IFN-α2b treatment should be considered as a component of future viral eradication strategies.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
54

participants targeted

Target at P25-P50 for phase_2 hiv

Timeline
Completed

Started Feb 2015

Typical duration for phase_2 hiv

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 25, 2014

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 28, 2014

Completed
6 months until next milestone

Study Start

First participant enrolled

February 11, 2015

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 7, 2018

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 24, 2018

Completed
Last Updated

April 5, 2018

Status Verified

April 1, 2018

Enrollment Period

3 years

First QC Date

August 25, 2014

Last Update Submit

April 3, 2018

Conditions

HIVHIV/AIDS

Keywords

HIVHIV-1PegintronPeg-IFN-α2bViral suppressionART cessationImmune functionInnate immunityToxicityImmune-based therapyTreatment interruptionHIV CureHIV EradicationBEAT-HIVHIV Cure TrialCure Trial

Outcome Measures

Primary Outcomes (1)

  • Integrated HIV proviral DNA

    The study endpoint is the change in the number of copies of integrated HIV DNA/10\^6 CD4+ T cells (as assessed by Alu-HIV gag PCR) between baseline and 20 weeks of peg-IFNα-2b administration (study week 24).

    24 weeks

Secondary Outcomes (3)

  • Integrated proviral DNA in tissue

    24 weeks

  • CD4 count

    24 weeks

  • Viral load

    24 weeks

Other Outcomes (1)

  • SUSAR (serious unexpected suspected adverse reactions)

    24 weeks

Study Arms (3)

Conditional 12-week ART interruption

EXPERIMENTAL

18 participants will receive peg-IFN-α2b (1 μg/kg/week) for 20 weeks.

Drug: Peg-IFN-α2b

Continuous ART

EXPERIMENTAL

18 participants will receive peg-IFN-α2b (1 μg/kg/week) for 20 weeks.

Drug: Peg-IFN-α2b

Control with continuous ART

NO INTERVENTION

18 participants will continue their current ART regimens and be observed for 20 weeks.

Interventions

Peg-IFN-α2bDRUG

Arm 1: At week 4 of the treatment, ART will be interrupted. Viral load will be monitored every 2 weeks. ART will be resumed at the earlier of a) a single measurement of VL \> 50 c/ml or b) 16 weeks of treatment, and subjects will be observed for the remaining 4 weeks (total of 20 weeks on treatment). Arm 2: In week 4, participants in arm 2 will add peg-IFN-α-2b to their ART regimen for a period of 20 weeks.

Also known as: Pegintron
Conditional 12-week ART interruptionContinuous ART

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age
  • Body weight ≥ 125 and ≤ 300 lbs
  • Confirmed diagnosis of HIV-1 infection by western blot or by a documented HIV-1 viral load at screening.
  • 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 if 1 or more measurements of \< 50 copies/ml are available no more than 3 months before and 3 months after the "blip" without change in ART
  • HIV viral load of \<50 copies/ml at screening.
  • CD4 \>450 cells/µL at screening.
  • a negative electrocardiogram (EKG, see section 7.4) for: a) men \>45 years or women \> 55 years of age b) younger subjects of either sex with two 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, c) subjects with a Framingham score \> 15% (men) or 10% (women)

You may not qualify if:

  • 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 Isoniazid, Pyrazinamide, Rifabutin, Rifampicin, Ganciclovir, Valgancyclovir, Oxymetholone, Thalidomide or Theophylline.
  • Ongoing treatment with anticoagulants
  • 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-α or γ (recombinant or pegylated), systemic corticosteroids (inhaled steroids allowed at the discretion of the Investigator); 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; polyribonucloside.
  • History of adverse or allergic reactions to any type-1 interferon (e.g. IFN-α2a, IFN-α2b, IFN-β)
  • Current or prior clinical conditions
  • History of severe depression, including history of suicidal ideation or attempt, 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 (i.e.: subjects with a history of diabetes mellitus and HA1C of \> 9 in the last 3 months or at screening).
  • Prior diagnosis of multiple sclerosis or other neurodegenerative disorders
  • Significant co-existing lab abnormalities including: a) Anemia (Hgb \<9.1 mg/dl men, \<8.9 mg/dl women); b) Ongoing coagulopathy/clotting disorder; c) WBC \<2000 cells/µl; d) Absolute neutrophil count (ANC) \<1200 cells/ µl; e) Platelet count \<60,000 cells/ µl; f) Liver disease (AST/ALT \> 2.5x OR total bilirubin \> 1.5x upper limits of norm (ULN), (if not receiving atazanavir) or direct bilirubin \> 0.6 (if receiving atazanavir); g) Pancreatic disease (amylase : \> 1.5 ULN, lipase \> 1.5 ULN, triglycerides \> 750 mg/dl); h Renal disease (creatinine \> 2x ULN 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.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Penn-Presbyterian Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Jonathan Lax Center at Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (4)

  • Azzoni L, Foulkes AS, Papasavvas E, Mexas AM, Lynn KM, Mounzer K, Tebas P, Jacobson JM, Frank I, Busch MP, Deeks SG, Carrington M, O'Doherty U, Kostman J, Montaner LJ. Pegylated Interferon alfa-2a monotherapy results in suppression of HIV type 1 replication and decreased cell-associated HIV DNA integration. J Infect Dis. 2013 Jan 15;207(2):213-22. doi: 10.1093/infdis/jis663. Epub 2012 Oct 26.

    PMID: 23105144BACKGROUND

  • Mexas AM, Graf EH, Pace MJ, Yu JJ, Papasavvas E, Azzoni L, Busch MP, Di Mascio M, Foulkes AS, Migueles SA, Montaner LJ, O'Doherty U. Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials. AIDS. 2012 Nov 28;26(18):2295-306. doi: 10.1097/QAD.0b013e32835a5c2f.

    PMID: 23014521BACKGROUND

  • Sun H, Buzon MJ, Shaw A, Berg RK, Yu XG, Ferrando-Martinez S, Leal M, Ruiz-Mateos E, Lichterfeld M. Hepatitis C therapy with interferon-alpha and ribavirin reduces CD4 T-cell-associated HIV-1 DNA in HIV-1/hepatitis C virus-coinfected patients. J Infect Dis. 2014 May 1;209(9):1315-20. doi: 10.1093/infdis/jit628. Epub 2013 Nov 25.

    PMID: 24277743BACKGROUND

  • Papasavvas E, Azzoni L, Kossenkov AV, Dawany N, Morales KH, Fair M, Ross BN, Lynn K, Mackiewicz A, Mounzer K, Tebas P, Jacobson JM, Kostman JR, Showe L, Montaner LJ. NK Response Correlates with HIV Decrease in Pegylated IFN-alpha2a-Treated Antiretroviral Therapy-Suppressed Subjects. J Immunol. 2019 Aug 1;203(3):705-717. doi: 10.4049/jimmunol.1801511. Epub 2019 Jun 28.

    PMID: 31253727DERIVED

Related Links

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

peginterferon alfa-2b

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Luis J. Montaner, DVM, DPhil

    The Wistar Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Immunology Program and Director, HIV-1 Immunopathogenesis Laboratory

Study Record Dates

First Submitted

August 25, 2014

First Posted

August 28, 2014

Study Start

February 11, 2015

Primary Completion

February 7, 2018

Study Completion

July 24, 2018

Last Updated

April 5, 2018

Record last verified: 2018-04

Locations

US(3)