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HIV InfectionsPhase 2NCT00594880

Antiviral Activity of Peg-IFN-Alpha-2A in Chronic HIV-1 Infection

A Phase 2 study testing Pegylated Interferon-alpha 2a, 180 mcg/week sc and Pegylated Interferon-alpha 2a, 90 mcg/week sc in people with HIV Infections, run by The Wistar Institute at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV Infections
What is being tested?
Pegylated Interferon-alpha 2a, 180 mcg/week sc and Pegylated Interferon-alpha 2a, 90 mcg/week sc
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
5 sitesUnited States
Study dates
Jan 2008to May 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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))

Who cannot join

  • 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
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  • 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
  • Hemoglobinopathies such as sickle cell anemia or Thalassemia major.
  • Hypersensitivity to Pegasys®or any of its components.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • Drexel University College of Medicine

    Philadelphia, Pennsylvania, 19102

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Penn-Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

  • The Wistar Institute

    Philadelphia, Pennsylvania, 19104

  • Jonathan Lax Immune Disorders Clinic

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

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.

Read the detailed description

The high toxicity of current Anti-Retroviral Therapy (ART) regimens has driven a number of studies investigating therapeutic approaches aimed at reducing drug exposure while maintaining the beneficial effects of immune reconstitution. Preliminary observations in HCV/HIV co-infected individuals already support an antiviral effect by Pegylated Interferon-Alpha-2A (Peg-IFN-Alpha-2A:Pegasys®) on HIV-1 replication; however, the ability of Peg-IFN-Alpha-2A (as a single agent) to maintain long-term suppression of HIV-1 replication in patients who interrupt ART after having achieved immune reconstitution remains undetermined. The rationale for addressing two doses of Peg-IFN-Alpha-2A (180 and 90 ug/week) is based on the antiviral activity reported with both doses and the lower incidence of adverse events associated with doses lower than that approved for HCV therapy (90 versus 180ug/week).

The long-range goal of this proposal is to determine if Peg-IFN-Alpha-2A monotherapy can sustain HIV-1 suppression in the absence of ART in infected individuals. Our short-range goal is to determine the safety, viral suppressive potential and immune correlates of Peg-IFN-Alpha-2A administered upon the cessation of suppressive ART.

Based on the current literature and our preliminary studies, we hypothesize that weekly doses of 90 or 180 ug/wk of Peg-IFN-Alpha-2A administered to pharmacologically-suppressed HIV-infected individuals in the course of antiretroviral therapy (ART) discontinuation will result in equivalent frequency of viral control, with the lower dose resulting in measurably lower rate and intensity of therapy-related adverse events (AE).

We propose to compare two different doses of Peg-IFN-Alpha-2A (90 or 180 ug/wk) as a simplification step to ART, for their ability to maintain viral load suppression when initiated 5 weeks before ART interruption in HIV-infected, ART-suppressed patients (VL<50 copies/ml). Briefly, control will be determined by the the percentages of viral load measurements <400 copies/ml between the two arms over a period of 24 weeks, corresponding to the Pegasys monotherapy period (exclusive of dual ART/Pegasys 5-week period). A threshold of 400 is used based on the known potential for blipping on ART between 50 and 400 copies/ml with no clinical consequence to sustained suppression thereafter (JAMA 2005, 293:817-829). Primary analysis will be an "intent to treat" analysis and will address the hypothesis that two different doses of Peg-IFN-Alpha-2A (90 and 180 ug/week) will be similarly effective at inhibiting viral replication.

The secondary objectives of the research are:

  1. To prospectively evaluate dose-dependent, treatment-associated toxicity, safety and tolerability of 29 weekly doses of Peg-IFN-Alpha-2A at 180 ug or 90 ug/week (in association with ART for the initial 5 weeks, followed by 24 weeks of Peg-IFN-Alpha-2A in the absence of ART).
  2. To determine innate immunity outcomes correlated to Peg-IFN-Alpha-2A dose and antiviral activity by monitoring Natural Killer (NK) and Dendritic cell (DC) subsets changes and the ability to maintain innate immune function (DC secretory responses, NK antiviral cytotoxic responses)
  3. To determine adaptive immunity outcomes correlated to Peg-IFN-Alpha-2A dose and antiviral activity by monitoring T-cell subsets changes and the ability to maintain cell-mediated proliferative and cytokine responses against recall antigens (anti-HIV-1 gag p55).
Conditions
HIV Infections
Being tested
Pegylated Interferon-alpha 2a, 180 mcg/week sc, Pegylated Interferon-alpha 2a, 90 mcg/week sc
Keywords
HIV, HIV-1, Pegasys, Peg-IFN-Alpha-2A, Viral Suppression, ART cessation, Immune function, Innate Immunity, Toxicity, Immune-based therapy, Treatment interruption
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pegylated Interferon-alpha 2a, 180 mcg/week scDrug

    Also called Pegasys

    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 scDrug

    Also called Pegasys

    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

Study groups in NCT00594880
Study groupRoleWhat they receive
Pegasys 180 mcg/weekActive comparatorART replacement treatment with Pegylated Interferon-alpha 2a, 180 mcg/week sc
Receives: Drug: Pegylated Interferon-alpha 2a, 180 mcg/week sc
Pegasys 90 mcg/weekActive comparatorART replacement treatment with Pegylated Interferon-alpha 2a, 90 mcg/week sc
Receives: Drug: Pegylated Interferon-alpha 2a, 90 mcg/week sc

What is being measured

The primary outcome is the main question the study is designed to answer.

  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%)

    Measured: 12 weeks

Secondary outcomes (2)
  1. HIV Viral Load < 48 Copies/ml

    % of individuals maintaining VL < 48 copies/ml while on pegylated interferon alpha-2a treatment without ART

    Measured: 12 weeks

  2. 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%)

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jan 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionNov 2010
  4. Study completionMay 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00594880
Sponsor's protocol ID
DAIDS-ES 10401
Other IDs
U01AI065279
Status last verified
Jan 2015
First submitted
4 Jan 2008
Last updated
10 Feb 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23105144
  • 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.

    PubMed 34049356
  • Chitre 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.

    PubMed 29505600

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pegylated Interferon-alpha 2a, 180 mcg/week sc and Pegylated Interferon-alpha 2a, 90 mcg/week sc in people with HIV Infections, run by The Wistar Institute at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HIV Viral Load < 400 Copies/ml (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00594880, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2015.

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