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

NCT03588715 | Unknown Phase 1 DMC FDA Drug

• 2 other identifiers: ES 38445UM1AI126620
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

HIV; HIV/AIDS; HIV-1 Infection

Keywords

HIV; HIV/AIDS; HIV Cure; HIV-1; HIV-1 Infection; BEAT-HIV; bNAbs; Broadly neutralizing antibodies

Outcome Measures

Primary Outcomes (3)

• Treatment-related adverse events during 30 week period of immunotherapy [Safety outcome]

  Number of participants with treatment-related adverse events during 30 weeks of peg-IFN-α2b administered at a weight adjusted dose weekly in combination with 3BNC117 and 10-1074 or the antibody combination alone.

  30 weeks of immunotherapy

• Association between antibody-mediated cell cytotoxicity (ADCC) and NK cell activation as measured by flowcytometry at start of step 4 therapy interruption and level of HIV plasma viral load 8 week later [Innate Activation outcome]

  Level of antibody-mediated cell cytotoxicity (ADCC) by direct measurement of NK cell CD107 degranulation against gp-120 coated targets in the presence of autologous plasma, and NK cell activation as measured by flowcytometry for frequency of cell subsets at start of step 4 therapy interruption. Values for ADCC cytotoxicity and NK activation will be tested by Spearman correlation test estimates with frequency of participants at \<50 during the end of immune treatment Interruption (Step 4)

  8 weeks after end of 30 week of immunotherapy (Analytical Treatment Interruption)

• Frequency of subjects with plasma viral load <50 copies/ml after end of step 4 after ART therapy interruption [Virological outcome]

  Frequency of participants remaining off ART with suppressed viral load (\<50 copies/ml) at 8 weeks after immune therapy interruption.

  8 weeks after end of 30 week of immunotherapy (Analytical Treatment Interruption)

Study Arms (2)

Pegylated Interferon alpha 2b + bNAbs

EXPERIMENTAL

Pegylated Interferon alpha 2b (peg-IFN-α2b) + bNAbs (3BNC117 + 10-1074)

Drug: Pegylated Interferon alpha 2b (peg-IFN-α2b); Drug: 3BNC117 + 10-1074

bNAb only

EXPERIMENTAL

bNAb (3BNC117 + 10-10-74) only

Drug: 3BNC117 + 10-1074

Interventions

Pegylated Interferon alpha 2b (peg-IFN-α2b) DRUG

Pegylated Interferon alpha 2b (peg-IFN-α2b) will be administered weekly via subcutaneous route.

Also known as: Pegintron

Pegylated Interferon alpha 2b + bNAbs

3BNC117 + 10-1074 DRUG

Broadly Neutralizing Antibodies - Sequential, separate IV infusions of 3NBC117 + 10-1074.

Also known as: Broadly Neutralizing Antibodies

Pegylated Interferon alpha 2b + bNAbs; bNAb only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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:

Sponsors & Collaborators

• Luis Montaner: lead
• University of Pennsylvania: collaborator
• Philadelphia Fight: collaborator
• Rockefeller University: collaborator
• Merck Sharp & Dohme LLC: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Jonathan Lax Center at Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (5)

• 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: 23105144 BACKGROUND

• Caskey M, Schoofs T, Gruell H, Settler A, Karagounis T, Kreider EF, Murrell B, Pfeifer N, Nogueira L, Oliveira TY, Learn GH, Cohen YZ, Lehmann C, Gillor D, Shimeliovich I, Unson-O'Brien C, Weiland D, Robles A, Kummerle T, Wyen C, Levin R, Witmer-Pack M, Eren K, Ignacio C, Kiss S, West AP Jr, Mouquet H, Zingman BS, Gulick RM, Keler T, Bjorkman PJ, Seaman MS, Hahn BH, Fatkenheuer G, Schlesinger SJ, Nussenzweig MC, Klein F. Antibody 10-1074 suppresses viremia in HIV-1-infected individuals. Nat Med. 2017 Feb;23(2):185-191. doi: 10.1038/nm.4268. Epub 2017 Jan 16.

  PMID: 28092665 BACKGROUND

• Scheid JF, Horwitz JA, Bar-On Y, Kreider EF, Lu CL, Lorenzi JC, Feldmann A, Braunschweig M, Nogueira L, Oliveira T, Shimeliovich I, Patel R, Burke L, Cohen YZ, Hadrigan S, Settler A, Witmer-Pack M, West AP Jr, Juelg B, Keler T, Hawthorne T, Zingman B, Gulick RM, Pfeifer N, Learn GH, Seaman MS, Bjorkman PJ, Klein F, Schlesinger SJ, Walker BD, Hahn BH, Nussenzweig MC, Caskey M. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016 Jul 28;535(7613):556-60. doi: 10.1038/nature18929. Epub 2016 Jun 22.

  PMID: 27338952 BACKGROUND

• Bilger A, Plenn E, Barg FK, Rendle KA, Carter WB, Lamour-Harrington A, Jones N, Peterson B, Sauceda JA, Tebas P, Mounzer K, Metzger D, Montaner LJ, Dube K. Participant experiences in HIV cure-directed trial with an extended analytical treatment interruption in Philadelphia, United States. HIV Res Clin Pract. 2023 Oct 6;24(1):2267825. Epub 2023 Oct 14.

  PMID: 37837376 DERIVED

• Neergaard R, Jones NL, Roebuck C, Rendle KA, Barbati Z, Peterson B, Tebas P, Mounzer K, Metzger D, Montaner LJ, Dube K, Barg FK. "I Know That I Was a Part of Making a Difference": Participant Motivations for Joining a Cure-Directed HIV Trial with an Analytical Treatment Interruption. AIDS Res Hum Retroviruses. 2023 Aug;39(8):414-421. doi: 10.1089/AID.2022.0040. Epub 2022 Sep 15.

  PMID: 35979886 DERIVED

Related Links

• Website for the BEAT-HIV Delaney Collaboratory, which is the funding mechanism for the clinical trial outlined in the current registry.

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

peginterferon alfa-2b; Broadly Neutralizing Antibodies

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Neutralizing; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Luis J Montaner, DVM, DPhil

  The Wistar Institute

  PRINCIPAL INVESTIGATOR

• Pablo Tebas, M.D.

  University of Pennsylvania

  STUDY CHAIR

• Karam Mounzer, M.D.

  Philadelphia Fight

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study will evaluate the impact of the combination of 3BNC117 and 10-1074 with or without antiretroviral therapy in virological rebound during an ATI and effects on the HIV reservoir. This will be a pilot phase I study to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of a combination of Pegylated Interferon alpha 2b with the two broadly neutralizing antibodies (3BNC117 and 10-1074) in 14 (all recruited first) individuals or the combination the broadly neutralizing antibodies alone in 7 (only 1 was able to be recruited due to COVID delays and drug availability) HIV-1 infected individuals, undergoing a brief analytical treatment interruption (ATI).

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: July 17, 2018
• Study Start: June 18, 2020
• Primary Completion: December 31, 2021
• Study Completion: October 30, 2022
• Last Updated: June 25, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)