HIVPhase 1BEAT-2NCT03588715

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

A Phase 1 study testing Pegylated Interferon alpha 2b (peg-IFN-α2b) and 3BNC117 + 10-1074 in people with HIV and HIV/AIDS, run by Luis Montaner at 2 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 The sponsor has not verified this record for over two years, so it may be out of date.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

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV, HIV/AIDS, HIV-1 Infection
What is being tested?: Pegylated Interferon alpha 2b (peg-IFN-α2b) and 3BNC117 + 10-1074
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 2 sitesUnited States
Study dates: 18 Jun 2020to 30 Oct 2022
Phase: Phase 1
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 36Show fewer

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
Complete Abstinence*
*Complete abstinence as defined as complete avoidance of heterosexual intercourse. Participants who choose complete abstinence are not required to use a second method of contraception. Acceptable alternate methods of highly effective contraception must be discussed in the event that the participant chooses to forego complete abstinence.
NOTE: Female partners of male participants participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug.
Negative HBsAg result obtained within 6 months prior to study entry.
HCV antibody negative result within 6 months prior to entry, or if the HCV antibody result is positive, a negative HCV RNA obtained within 6 months prior to study entry. Treated and cured HCV infected participants are allowed.
Adequate venous access in at least one arm
Body weight ≥ 125 and ≤ 300 lbs
A non-clinically significant electrocardiogram (EKG, see section 7.2) for:
men >45 years or women > 55 years of age
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
subjects with a Framingham score > 15% (men) or 10% (women)

Who cannot join

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

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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
Hydroxyurea
Thalidomide
Pentoxifylline
Thymopentin, thymosin
Dithiocarbonate
Polyribonucleoside.
History of adverse or allergic reactions to any type-1 interferon (e.g. IFN-α2a, IFN-α2b, IFN-β)
Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer, including, clinically significant forms of:
Drug or alcohol abuse
Severe asthma
Uncontrolled hypertension
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)
Psychiatric disorders, including severe depression and/or suicidal ideation
Heart disease
Cancer or hematologic malignancies
Prior diagnosis of multiple sclerosis or other neurodegenerative disorders
Liver cirrhosis or hepatic decompensation
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 at 24 weeks post treatment prior to screening are eligible for enrollment.
Major organ transplantation with an existing functional graft
Active autoimmune diseases, including autoimmune hepatitis
History of retinopathy or clinically significant ophthalmologic disease
Opportunistic infections or other active infectious diseases
Other conditions, such as active drug/alcohol abuse or dependence, that in the opinion of the Investigator would interfere with study compliance.
Initiation of treatment during acute infection

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Jonathan Lax Center at Philadelphia FIGHT
Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: Pilot Study on Innate Activation and Viral Control in HIV-Infected Adults Undergoing an Analytical Treatment Interruption After Administration of Pegylated Interferon Alpha 2b With Broadly HIV-1 Neutralizing Antibodies (3BNC117, 10-1074)

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.

Read the detailed description

The proposed 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. This 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 participants with well-controlled HIV infection. A review of the conceptual framework for the strategy to be tested includes:

Why peg-IFN-α2? The therapeutic effects of peg-IFN-α2 yield two essential outcomes that are the fundamental objectives of HIV curative strategies: control viral replication in the absence of ART and reduce the levels of integrated HIV DNA in CD4+ T-cells. To date, peg-IFN-α is the only intervention that has been shown to maintain viral suppression to levels <50 copies/mL in the absence of ART in chronic infection. Preliminary data supports that correlates of anti-HIV reductions are centered on activation of NK responses.
Why bNAbs + peg-IFN-α2b? The addition of bNAbs may act independently to control virus replication or decrease fitness thereby increasing the potential for a larger antiviral effect after IFN by enhance NK-mediated clearance via a reduced viral levels and the complementarity of bNAbs in enhancing mechanisms of antibody-mediated cytotoxicity against infected cells by binding to virus emerging from or viral proteins expressed on activated latent cells.
Why combined bNAbs? In vivo, multiple bNAbs targeting different epitopes provide better neutralization and antigen recognition than single bNAbs, which suggests that adoptive transfer of multiple bNAbs may lead to superior viral control. Although bNAbs may have neutralization effects that are of greater clinical impact than ADCC, it is possible that antigen targeting through multiple bNAbs may also enhance NK-mediated cytotoxicity more than a single bNAb. The administration of broadly neutralizing antibodies alone in the setting of an analytical treatment interruption delays the return of viremia in a fraction of the participants.
Why test an ATI of immunotherapy? To date, peg-IFN-α2 administered prior to an ATI or ART and subsequently maintained throughout the ATI period has maintained viral suppression. An effective curative strategy requires that all interventions be discontinued.

Conditions: HIV, HIV/AIDS, HIV-1 Infection
Being tested: Pegylated Interferon alpha 2b (peg-IFN-α2b), 3BNC117 + 10-1074
Keywords: HIV, HIV/AIDS, HIV Cure, HIV-1, HIV-1 Infection, BEAT-HIV, bNAbs, Broadly neutralizing antibodies
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.

Pegylated Interferon alpha 2b (peg-IFN-α2b)Drug
Also called Pegintron
Pegylated Interferon alpha 2b (peg-IFN-α2b) will be administered weekly via subcutaneous route.
3BNC117 + 10-1074Drug
Also called Broadly Neutralizing Antibodies
Broadly Neutralizing Antibodies - Sequential, separate IV infusions of 3NBC117 + 10-1074.

Study groups in NCT03588715
Study group	Role	What they receive
Pegylated Interferon alpha 2b + bNAbs	Experimental	Pegylated Interferon alpha 2b (peg-IFN-α2b) + bNAbs (3BNC117 + 10-1074) Receives: Drug: Pegylated Interferon alpha 2b (peg-IFN-α2b); Drug: 3BNC117 + 10-1074
bNAb only	Experimental	bNAb (3BNC117 + 10-10-74) only Receives: Drug: 3BNC117 + 10-1074

What is being measured

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

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

Timeline

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

18 Jun 202030 Oct 2022

First posted17 Jul 2018
Study start18 Jun 2020
Primary completion31 Dec 2021 (estimated)
Study completion30 Oct 2022 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for HIVStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: 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).
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03588715
Sponsor's protocol ID: ES 38445
Other IDs: UM1AI126620
Acronym: BEAT-2
Status last verified: Jun 2020
First submitted: 30 Apr 2018
Last updated: 25 Jun 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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
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.
PubMed 28092665
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.
PubMed 27338952
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.
PubMed 37837376
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.
PubMed 35979886

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study on Innate Activation and Viral Control in HIV-Infected Adults Undergoing an Analytical Treatment Interruption After Administration of Pegylated Interferon Alpha 2b With Broadly HIV-1 Neutralizing Antibodies (3BNC117, 10-1074)
ClinicalTrials.gov ID: NCT03588715
Acronym / sponsor ID: BEAT-2 / ES 38445
Conditions: HIV, HIV/AIDS, HIV-1 Infection
Keywords: HIV, HIV/AIDS, HIV Cure, HIV-1, HIV-1 Infection, BEAT-HIV, bNAbs, Broadly neutralizing antibodies
Phase: Phase 1
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 15 participants (actual)
Lead sponsor: Luis MontanerUniversity, hospital or other
Collaborators: University of Pennsylvania, Philadelphia Fight, Rockefeller University, Merck Sharp & Dohme LLC, National Institute of Allergy and Infectious Diseases (NIAID)
Study start: 18 Jun 2020 (actual)
Primary completion: 31 Dec 2021 (estimated)
Study completion: 30 Oct 2022 (estimated)
First posted: 17 Jul 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Why peg-IFN-α2? The therapeutic effects of peg-IFN-α2 yield two essential outcomes that are the fundamental objectives of HIV curative strategies: control viral replication in the absence of ART and reduce the levels of integrated HIV DNA in CD4+ T-cells. To date, peg-IFN-α is the only intervention that has been shown to maintain viral suppression to levels <50 copies/mL in the absence of ART in chronic infection. Preliminary data supports that correlates of anti-HIV reductions are centered on activation of NK responses.
Why bNAbs + peg-IFN-α2b? The addition of bNAbs may act independently to control virus replication or decrease fitness thereby increasing the potential for a larger antiviral effect after IFN by enhance NK-mediated clearance via a reduced viral levels and the complementarity of bNAbs in enhancing mechanisms of antibody-mediated cytotoxicity against infected cells by binding to virus emerging from or viral proteins expressed on activated latent cells.
Why combined bNAbs? In vivo, multiple bNAbs targeting different epitopes provide better neutralization and antigen recognition than single bNAbs, which suggests that adoptive transfer of multiple bNAbs may lead to superior viral control. Although bNAbs may have neutralization effects that are of greater clinical impact than ADCC, it is possible that antigen targeting through multiple bNAbs may also enhance NK-mediated cytotoxicity more than a single bNAb. The administration of broadly neutralizing antibodies alone in the setting of an analytical treatment interruption delays the return of viremia in a fraction of the participants.
Why test an ATI of immunotherapy? To date, peg-IFN-α2 administered prior to an ATI or ART and subsequently maintained throughout the ATI period has maintained viral suppression. An effective curative strategy requires that all interventions be discontinued.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: 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).

Arm	Type	Receives
Pegylated Interferon alpha 2b + bNAbs	Experimental	Drug: Pegylated Interferon alpha 2b (peg-IFN-α2b), Drug: 3BNC117 + 10-1074Pegylated Interferon alpha 2b (peg-IFN-α2b) + bNAbs (3BNC117 + 10-1074)
bNAb only	Experimental	Drug: 3BNC117 + 10-1074bNAb (3BNC117 + 10-10-74) only

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (36 listed)

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

Key exclusion criteria (49 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Pegylated Interferon alpha 2b (peg-IFN-α2b)Also: PegintronPegylated Interferon alpha 2b (peg-IFN-α2b) will be administered weekly via subcutaneous route.	Drug	Pegylated Interferon alpha 2b + bNAbs
3BNC117 + 10-1074Also: Broadly Neutralizing AntibodiesBroadly Neutralizing Antibodies - Sequential, separate IV infusions of 3NBC117 + 10-1074.	Drug	Pegylated Interferon alpha 2b + bNAbs, bNAb only

Primary outcome

Treatment-related adverse events during 30 week period of immunotherapy [Safety outcome]
Time frame: 30 weeks of immunotherapy
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.
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]
Time frame: 8 weeks after end of 30 week of immunotherapy (Analytical Treatment Interruption)
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)
Frequency of subjects with plasma viral load <50 copies/ml after end of step 4 after ART therapy interruption [Virological outcome]
Time frame: 8 weeks after end of 30 week of immunotherapy (Analytical Treatment Interruption)
Frequency of participants remaining off ART with suppressed viral load (<50 copies/ml) at 8 weeks after immune therapy interruption.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2021.
Background: PubMed 23105144Azzoni 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.
Background: PubMed 28092665Caskey 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.
Background: PubMed 27338952Scheid 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.
Derived from this study: PubMed 37837376Bilger 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.
Derived from this study: PubMed 35979886Neergaard 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.
Website for the BEAT-HIV Delaney Collaboratory, which is the funding mechanism for the clinical trial outlined in the current registry.Link provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Luis J Montaner, DVM, DPhil principal investigator

The Wistar Institute

Pablo Tebas, M.D. study chair

University of Pennsylvania

Karam Mounzer, M.D. study director

Philadelphia Fight

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pegylated Interferon alpha 2b (peg-IFN-α2b) and 3BNC117 + 10-1074 in people with HIV and HIV/AIDS, run by Luis Montaner at 2 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 36 inclusion and 49 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 25 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Treatment-related adverse events during 30 week period of immunotherapy [Safety outcome] (time frame: 30 weeks of immunotherapy). The study lists 3 primary outcomes in all. 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 NCT03588715, which also lists 5 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 25 Jun 2021.