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HIVPhase 2BEAT-HIVNCT02227277

Reducing Proviral HIV DNA With Interferon-a

A Phase 2 study testing Peg-IFN-α2b in people with HIV and HIV/AIDS, run by The Wistar Institute at 3 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
HIV, HIV/AIDS
What is being tested?
Peg-IFN-α2b
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
3 sitesUnited States
Study dates
11 Feb 2015to 24 Jul 2018
Phase
Phase 2
Are there results?
None posted in the registry

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

  • 18-65 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)

Who cannot join

  • 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.
Show all 25Show fewer
  • 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.
  • 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 60 days prior to initiation of IFN
  • Significant EKG abnormalities (see section 7.4)
  • Other conditions
  • Pregnancy or breastfeeding
  • A planned pregnancy during study participation
  • Lack of one of three strategies for birth control during study participation: a) Barrier contraceptives (male or female condoms with or without a spermicidal agent, diaphragm or cervical cap with spermicidal); b) Non-hormonal Intrauterine Devices (IUDs); c) Hormonal-based, including hormonal IUDs, in combination with barrier contraceptives.
  • Body weight < 125 lbs or > 300 lbs
  • Other conditions, such as active drug/alcohol abuse or dependence,that in the opinion of the Investigator would interfere with study compliance.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Penn-Presbyterian Hospital

    Philadelphia, Pennsylvania, 19104

  • Jonathan Lax Center at Philadelphia FIGHT

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Towards Eradication: Reducing Proviral HIV DNA With Interferon-a Immunotherapy

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.

Read the detailed description

Our long-term goal is to evaluate the effect of pegylated interferon (peg-IFN) α as an anti-HIV reservoir immunotherapy that could potentiate eradication strategies against HIV.

The present study is a 3-arm randomized clinical trial (RCT). The aim of this study is to determine whether a 20-week treatment course with 1μg/kg/week of pegylated interferon alpha 2 b (peg-IFN-α2b) will reduce the levels of HIV-1 proviral DNA levels in circulating PBMC and mucosa-associated lymphoid tissue (MALT) in HIV-infected individuals receiving long-term ART.

In addition, we will study if a 4-week interruption of ART is necessary to observe any change in proviral DNA levels.

In our previous study (NCT00594880) with a different form of Interferon alpha (peg-IFN-α2a), we observed a reduction in proviral DNA in peripheral blood cells in 50% of the patients. However, we did not measure the levels in MALT, and we could not determine whether or not an interruption of ART was necessary. The present study will address these questions.

We will also seek to determine the biological mechanisms (such as an increase in Natural Killer cell cytotoxicity) that mediate the antiviral effects of peg-IFN-α.

Conditions
HIV, HIV/AIDS
Being tested
Peg-IFN-α2b
Keywords
HIV, HIV-1, Pegintron, Peg-IFN-α2b, Viral suppression, ART cessation, Immune function, Innate immunity, Toxicity, Immune-based therapy, Treatment interruption, HIV Cure, HIV Eradication, BEAT-HIV, HIV Cure Trial, Cure Trial
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

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

  • Peg-IFN-α2bDrug

    Also called Pegintron

    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.

Study groups in NCT02227277
Study groupRoleWhat they receive
Conditional 12-week ART interruptionExperimental18 participants will receive peg-IFN-α2b (1 μg/kg/week) for 20 weeks.
Receives: Drug: Peg-IFN-α2b
Continuous ARTExperimental18 participants will receive peg-IFN-α2b (1 μg/kg/week) for 20 weeks.
Receives: Drug: Peg-IFN-α2b
Control with continuous ARTNo intervention18 participants will continue their current ART regimens and be observed for 20 weeks.

What is being measured

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

  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).

    Measured: 24 weeks

Secondary outcomes (3)

  1. Integrated proviral DNA in tissue

    Copies of HIV DNA per tissue derived 2x106 isolated lymphocytes (GALT biopsy)-recovered lymphocyte (week 0 vs. week 24)

    Measured: 24 weeks

  2. CD4 count

    compare the frequency of occurrence of CD4 count < 350 (trigger to resume ART during ART interruption in arm 1) between study arms

    Measured: 24 weeks

  3. Viral load

    compare the frequency of occurrence of VL > 50 copies/ml (trigger for resuming ART during ART interruption in arm 1) between arms

    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 posted28 Aug 2014 (estimated)
  2. Study start11 Feb 2015
  3. Primary completion7 Feb 2018
  4. Study completion24 Jul 2018 (estimated)

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
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02227277
Sponsor's protocol ID
ES11990
Other IDs
1U01AI110434
Acronym
BEAT-HIV
Status last verified
Apr 2018
First submitted
25 Aug 2014
Last updated
5 Apr 2018
Results posted
No
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

  • 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.

    PubMed 23014521

  • 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.

    PubMed 24277743

  • 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.

    PubMed 31253727

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Peg-IFN-α2b in people with HIV and HIV/AIDS, run by The Wistar Institute at 3 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 8 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

Results are not available in the source record.

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?

Integrated HIV proviral DNA (time frame: 24 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 NCT02227277, which also lists 4 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 5 Apr 2018.

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Reducing Proviral HIV DNA With Interferon-a | AzTrials