Peg-Interferon Alpha 2b Combined With Two Intravenous Broadly HIV-1 Neutralizing Antibodies 3BNC117 and 10-1074 (BEAT-2)

Status unconfirmed · Phase 1

Conditions studied: HIV, HIV/AIDS, HIV-1 Infection

In brief

This study will evaluate the safety, tolerability and innate immune mechanisms activation following administration of the combination of Pegylated Interferon alpha 2b (peg-IFN-α2b) with two broadly neutralizing antibodies (3BNC117 and 10-1074) in the setting of well-controlled HIV infection with antiretroviral treatment and a monitored analytical treatment interruption. The current proposal builds on previous experience using interferon alpha, 3BNC117 and 10-1074 alone in separate clinical trials that included a closely monitored analytical treatment interruption. The hypothesis is that the joint administration of peg-IFN-α2b with 3BNC117 and 10-1074 will be more effective than either intervention separately in suppressing HIV viremia during 8 weeks of analytical treatment interruption (Step 4) and reducing integrated HIV DNA in blood and tissue when measured during an analytical treatment interruption in patients with well-controlled HIV infection.

Key facts

Study ID

NCT03588715

Run by

Luis Montaner

People needed

15

Starts

2020-06-18

Expected to finish

2022-10-30

Last updated by the study team

2021-06-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL
• Ability and willingness of participant to provide informed consent
• Men and women aged ≥18 years
• Clinically stable on their first or second ART regimen that includes a boosted protease inhibitor or an integrase inhibitor. The current regimen should be stable for 4 weeks at the time of entry. Changes while the patient HIV viral load is undetectable does not count toward the number of ART regimens used, (for example an individual switching from an NNRTI-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable will still be in their first regimen)
• HIV-1 RNA that is <50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 56 days prior to study entry
• NOTE: HIV-1 RNA must be measured at least once in the 24 weeks prior to entry and at least 3 days before the screening measure. Single determinations that are between ≥50 and <400 copies/mL (i.e., blips) are allowed as long as the preceding and subsequent determinations are <50 copies/mL. The screening value may serve as the subsequent determination <50 copies/mL following a blip
• Screening CD4+ T-cell count ≥450 cells/μL within 45 days prior to study entry
• Willingness to have blood samples collected and used for study-related research purposes
• The following laboratory values obtained within 45 days prior to enrollment:
• Absolute neutrophil count (ANC) ≥1000 cells/mm3
• Hemoglobin ≥12.0 g/dL for men and ≥11 g/dL for women
• Platelet count 100,000/mm3
• Creatinine clearance ≥60 mL/min estimated by the Cockcroft-Gault equation
• Alanine aminotransferase (ALT) ≤2.5 x ULN
• Pancreatic amylase ≤ 1.5 ULN and lipase ≤ 1.5 ULN and triglycerides ≤ 750 mg/dl
• total bilirubin ≤ 1.5x ULN, (if not receiving atazanavir) OR direct bilirubin ≤ 1 mg/dl (if receiving atazanavir)
• For females of reproductive potential (i.e., women who have not been post-menopausal for at least 24 consecutive months, who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy), negative urine pregnancy test (with a sensitivity of 15-25 mIU/mL) within 48 hours prior to screening and entry.
• ADDITIONAL REQUIREMENTS BIOLOGICAL FEMALES ARE NOTED IN CLINICAL PROTOCOL.
• Female partners of reproductive potential of male study participants on study drug would be educated that:
• At least two of the following contraceptives MUST be used appropriately by female partners of reproductive potential of male study participants and/or their male partners with one method being highly effective and the other method being either highly effective or less effective as listed below:
• Highly Effective Methods of Contraception
• Male condoms with spermicide
• Hormone-based contraceptives including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUDs) such as Mirena by male participant's female partner of reproductive potential.
• Nonhormonal IUDs, such as ParaGard
• Tubal ligation

You may not qualify if…

• Susceptibility to bNAb 10-1074 based on IC90 greater than 2.0 µg/mL or susceptibility to bNAb 3BNC117 based on IC90 greater than 1.5 µg/mL using the Monogram Phenosense Assay on sample obtained on ART in absence of a subsequent documentation of a HIV viral load of greater than 1,000 copies on a collection date after that of the bNAb sensitivity sample.
• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational
• Weight >300 lbs or <125 lbs
• History of an AIDS-defining illness
• Ongoing AIDS-related opportunistic infection (including oral thrush)
• History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment
• Currently pregnant, breastfeeding, or planning pregnancy
• Receipt of other investigational study agent within 30 days prior to enrollment
• Current or prior medications:
• 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

Where it is running

• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States
• Jonathan Lax Center at Philadelphia FIGHT — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

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