Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection
2 other identifiers
interventional
23
1 country
5
Brief Summary
The objective of the study is to compare two different doses of Peg-INF-α-2A (90 or 180 ug/wk) for their ability to maintain viral control when initiated 5 weeks before ART (antiretroviral therapy) interruption in HIV positive, ART-suppressed subjects (viral load \<50 copies/ml) as determined by observing the percentages of viral load measurements \<400 copies/ml between the two arms over a 24-week period, corresponding to the Pegasys monotherapy period (exclusive of dual ART/Pegasys 5-week period). Primary analysis will be an "intent to treat" analysis and will address the hypothesis that two different doses of Peg-INF-α-2A (90 and 180 ug/week) will be similarly effective at inhibiting viral replication.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 hiv-infections
Started Jan 2008
Typical duration for phase_2 hiv-infections
5 active sites
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
Study Start
First participant enrolled
January 1, 2008
CompletedFirst Submitted
Initial submission to the registry
January 4, 2008
CompletedFirst Posted
Study publicly available on registry
January 16, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2011
CompletedResults Posted
Study results publicly available
February 10, 2015
CompletedFebruary 10, 2015
January 1, 2015
2.8 years
January 4, 2008
January 24, 2013
January 28, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
HIV Viral Load < 400 Copies/ml
% of individuals maintaining viral suppression (VL \< 400 copies/ml) as compared to the anticipated rate of viral suppression in individuals interrupting ART without interferon (9%)
12 weeks
Secondary Outcomes (2)
HIV Viral Load < 48 Copies/ml
12 weeks
HIV Viral Load < 400 Copies/ml
24 weeks
Study Arms (2)
Pegasys 180 mcg/week
ACTIVE COMPARATORART replacement treatment with Pegylated Interferon-alpha 2a, 180 mcg/week sc
Pegasys 90 mcg/week
ACTIVE COMPARATORART replacement treatment with Pegylated Interferon-alpha 2a, 90 mcg/week sc
Interventions
Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL \< 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints
Pegylated Interferon-alpha 2a, 90 mcg/week sc for 24 weeks, 5 weeks in combination with ART, then 7 weeks without ART to primary endpoint (VL \< 400 c/ml at 12 weeks) and further 12 weeks without ART (24 weeks) to secondary endpoints
Eligibility Criteria
You may qualify if:
- Male or female, age ≥ 18 but \<65 years
- Able and willing to provide informed consent.
- HIV-1 infection documented by any licensed enzyme-linked immunosorbent assay (ELISA) test kit and confirmed by Western Blot at any time prior to or at study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test
- HIV RNA \< 75 copies/ml on a regimen of a) 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and 1 non-nucleoside RTI (NNRTI) OR b) 2 NRTIs and Protease Inhibitor (PI) for at least 24 weeks OR c) 3 NRTIs
- HIV RNA \< 75 copies/ml at screening
- \> 6 months ≥ 400 CD4+ T cells/mm3 (CD4 nadir ≥ 200 cells)
- Female subjects with childbearing potential: negative pregnancy test (Beta human horionic gonadotropin (HCG)). Must agree to use appropriate contraceptive methods (barrier devices such as diaphragms or condoms + spermicidal or intrauterine device (IUD) or oral contraceptives) while on study.
- Karnofsky performance scale score of 80% or better
- Willing to adhere to the treatment and schedule approved by the study investigators in conjunction with the patient's primary provider.
- Willing to abstain from immunomodulatory drugs during the study period, with the exception of the study drug (Pegasys®).
- Patient Health Questionnaire (PHQ)-2 score \< 2, OR PHQ-9 score\< 10, OR PHQ-9 score 10-14 AND medical provider's favorable opinion. In either case, score for PHQ-9 question # 9 (suicidal ideation) must be 0.
- Thyroid stimulating hormone (TSH) within normal range, unless accompanied by thyroid profile consistent with normal thyroid function
- A negative cardiac stress test 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 \[smoking, hypertension (BP \>140/90 or on antihypertensive medications), low Hight density lipoprotein (HDL)-associated cholesterol (\<40 mg/dL), family history of premature Coronary heart disease (CHD) (\<55 yrs males/\<65 females)\] or a Framingham score \> 15% (men) or 10% (women))
You may not qualify if:
- Currently pregnant or breast feeding.
- CD4 cell count \< 400 or recorded CD4 nadir \< 200 cells/mm3
- History of immunomodulatory therapy for over 2 weeks during the 6 months prior to enrollment, including, but not limited to: IFN-Alpha or Beta (recombinant or pegylated), systemic corticosteroids; 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; polyribonucleoside.
- Significant co-existing medical conditions including: Anemia (Hgb \<9.1 men, \<8.9 women), Neutropenia (ANC \< 1000), Thrombocytopenia (platelet count \<50K), Liver disease (AST/ALT \> 5x, Total Bilirubin \> 1.5x upper limits of normal, or Total Bilirubin \>3x upper limit of the norm (ULN) if receiving indinavir), Renal disease (creatinine \> 2x upper normal limits), or other conditions, such as active drug/alcohol abuse or dependence which would interfere with study compliance.
- Any history of heart attacks, myocardial infarction or coronary arterial disease (MI/CAD). .
- Prior history of major depression or other severe psychiatric disorder/condition requiring treatment and/or hospitalization
- PHQ-9 score \>14, OR PHQ-9 score \> 10 - 14 and lack of medical provider's favorable opinion, or score for PHQ-9 answer # 9 (suicidal ideation) \> 0.
- Evidence of chronic active Hepatitis B infection (Surface Antigen HBsAg) or Hepatitis C plymerase chain reaction (PCR) positivity at screening (cleared of HCV at entry \>6 months).
- Past evidence of medical conditions associated with chronic liver disease including genetic hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures etc.
- History of neutropenia or other hematological abnormalities
- Type I diabetes mellitus, or type II diabetes mellitus that is not controlled with oral agents and/or insulin.
- Ongoing treatment with Isoniazide, Pyrazinamide, Rifabutin, Rifampicin, Diadenosine Ganciclovir, Valganciclovir, Oxymetholone, Thalidomide or Theophylline.
- History of autoimmune processes including Crohn's disease, ulcerative colitis, severe psoriasis, rheumatoid arthritis, myositis, hepatitis etc.
- History of major organ transplantation with an existing functional graft.
- Active coronary artery disease within 24 weeks prior to study
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Wistar Institutelead
- National Institutes of Health (NIH)collaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
- Hoffmann-La Rochecollaborator
Study Sites (5)
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Penn-Presbyterian Medical Center
Philadelphia, Pennsylvania, 19104, United States
The Wistar Institute
Philadelphia, Pennsylvania, 19104, United States
Jonathan Lax Immune Disorders Clinic
Philadelphia, Pennsylvania, 19107, United States
Related Publications (3)
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: 23105144RESULTPapasavvas 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.
PMID: 34049356DERIVEDChitre AS, Kattah MG, Rosli YY, Pao M, Deswal M, Deeks SG, Hunt PW, Abdel-Mohsen M, Montaner LJ, Kim CC, Ma A, Somsouk M, McCune JM. A20 upregulation during treated HIV disease is associated with intestinal epithelial cell recovery and function. PLoS Pathog. 2018 Mar 5;14(3):e1006806. doi: 10.1371/journal.ppat.1006806. eCollection 2018 Mar.
PMID: 29505600DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
The follwing limitations of this study should be noted: * Small number of participants enrolled * Lack of a control arm interrupting ART without immunotherapy
Results Point of Contact
- Title
- Luis Montaner
- Organization
- the Wistar Institute
Study Officials
- STUDY CHAIR
Luis Montaner, DVM, PhD
The Wistar Institute
- PRINCIPAL INVESTIGATOR
Jay Kostman, MD
Penn-Presbyterian Medical Center
- PRINCIPAL INVESTIGATOR
Pablo Tebas, MD
University of Pennsylvania
- PRINCIPAL INVESTIGATOR
Jeffrey Jacobson, MD
Drexel University College of Medicine
- PRINCIPAL INVESTIGATOR
Karam Mounzer, MD
Jonathan Lax Immune Disorders Clinic- Philadelphia FIGHT
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
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
- Protocol Chair / Prinicipal Investigator
Study Record Dates
First Submitted
January 4, 2008
First Posted
January 16, 2008
Study Start
January 1, 2008
Primary Completion
November 1, 2010
Study Completion
May 1, 2011
Last Updated
February 10, 2015
Results First Posted
February 10, 2015
Record last verified: 2015-01