Combination Therapy With 3BNC117 and 10-1074 in HIV-Infected Individuals

NCT03571204 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 18011518-I-0115
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Human immunodeficiency virus (HIV) affects the immune system. The main function of the immune system is protect you from infections and other diseases such as cancer. HIV attacks and cripples the immune system making people more susceptible to a variety of infections and cancers. Currently, the standard treatment for HIV infection is a daily administration of anti-HIV drugs. These drugs are called combination antiretroviral therapy (ART). ART is very effective at suppressing HIV, but does not cure HIV infection. ART must be taken continuously for life to be effective. ART can stop being effective if not taken correctly and can cause permanent side effects. Researchers want to see if two new products can control HIV infection without the use of ART. The products are the antibodies 3BNC117 and 10-1074. Objective: To see if 3BNC117 and 10-1074 are safe and can control HIV levels in the blood of people who are not taking ART or people who stop taking their ART during the study. . Eligibility: Adults ages 18-65 with HIV who are:

• on ART and willing to stop treatment for at least 28 weeks
• OR not taking ART with low levels of HIV in the blood Design: Participants will be screened with a physical exam, medical history, and blood, heart, and urine tests. Participants will get the 2 study products or salt water (placebo). A thin tube will be placed in an arm vein. Each product will be given directly into the vein for about 1 hour. To help collect blood cells to study in the laboratory, participants may have a procedure known as leukapheresis in which blood will be removed through a needle in the arm. Some of the white blood cells will be separated from the blood and used for research studies to see how 3BNC117 and 10-1074 effects HIV and the immune system. The rest of the blood will be returned to the person through another needle in the arm. Participants will have 18 study visits over 28 weeks. They will repeat some screening tests. They may have leukapheresis again. At 8 study visits, participants will get the study products or placebo. All participants will be followed for at least 24 weeks after their last dose of the study infusions. Participants who are in the Group that stops ART will be monitored closely to make sure the levels of virus in their blood do not go to high. If at any time during this the study a person develops HIV-related symptoms, or if the viral levels go up to high levels for more than 4 weeks, ART will be restarted and no further infusions of 3BNC117 and 10-1074 will be given. ...

Conditions

HIV

Keywords

Treatment Interruption; Neutralizing Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Participants With Grade 3 or Higher Adverse Events

  Participants with grade 3 or higher adverse events (AE), including serious adverse advents. AE severity was graded according to the Division of Aids Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.1, July, 2017

  29 months

Secondary Outcomes (2)

• Participants Who Experienced Rebound of Plasma Viremia

  28 weeks

• Participants Who Achieved Suppression of Viremia

  28 weeks

Study Arms (3)

Group 1: ART prior to 3BNC117 + 10-1074 in HIV-1 subject

ACTIVE COMPARATOR

Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.

Biological: 3BNC117 and 10-1074

Group 1: ART prior to placebo treatment in HIV-1 subject

PLACEBO COMPARATOR

Subjects who began anti-retroviral therapy (ART) during primary HIV-1 infection within 12 weeks of diagnosis. ART was stopped after study day 3 and were given normal saline intravenously. Subjects received two separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.

Biological: Placebo

Group 2: 3BNC117 + 10-1074 in HIV-1 subject

EXPERIMENTAL

Subjects who were not on anti-retroviral therapy (ART) during primary HIV-1 infection within the past 2 years. Subjects were given 3BNC117 and 10-1074 intravenously. Both 3BNC117 and 10-1074 were administered at 30 mg/kg dose level in separate bags of 250 mL normal saline in sequential administration. Subjects received 8 infusions of 3BNC117 and 10-1074 at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The total duration of therapy was 24 weeks.

Biological: 3BNC117 and 10-1074

Interventions

3BNC117 and 10-1074 BIOLOGICAL

Both 3BNC117 and 10-1074 administered intravenously at 30 mg/kg dose level in 250 ml normal saline for 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The two antibodies will be mixed in separate bags of saline for sequential administration.

Group 1: ART prior to 3BNC117 + 10-1074 in HIV-1 subject; Group 2: 3BNC117 + 10-1074 in HIV-1 subject

Placebo BIOLOGICAL

Placebo is two separate bags of 250 ml normal saline administered intravenously for 8 infusions at weeks 0, 2, 4, 8, 12, 16, 20, and 24. The two separate bags of placebo are administered sequentially.

Group 1: ART prior to placebo treatment in HIV-1 subject

Eligibility Criteria

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

You may qualify if:

• Age 18-65 years old.
• HIV-1 infection and clinically stable.
• General good health and has an identified primary health care provider for medical management of HIV infection and is willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
• Cluster of differentiation 4 (CD4)+ T cell count \>450 cells/mm(3) at screening.
• Laboratory values within pre-defined limits at screening:
• Absolute neutrophil count \>1,000/mm(3).
• Hemoglobin levels \>10.0 g/dL for men and \>9.0 g/dL for women.
• Platelet count \>100,000/mm(3).
• Estimated or a measured glomerular filtration rate \>60 mL/min/1.73m(2) as determined by the National Institutes of Health (NIH) Clinical Center laboratory.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of \<2.5 times upper limit of normal (ULN), direct bilirubin within the normal range for the NIH Clinical Center laboratory.
• Willingness to have samples stored for future research.
• Institution of ART within 12 weeks of being diagnosed with primary HIV-1 infection
• Primary HIV-1 infection is defined as meeting at least one of the following criteria:
• Detectable plasma HIV-1 RNA levels of \>2000 copies/mL with a negative result from an HIV-1 enzyme immunoassays (EIA), or
• Positive result from an HIV-1 EIA with a negative or indeterminate result from an HIV-1 western blot or another confirmatory antibody test that subsequently evolves to a confirmed positive result, or

You may not qualify if:

• Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen
• (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
• HIV immunotherapy or vaccine(s) received within 1 year prior to screening.
• Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.
• Receipt of other investigational study agent within 28 days of enrollment.
• Any active malignancy that may require systemic chemotherapy or radiation therapy.
• Systemic immunosuppressive medications received within 3 months prior to enrollment (Not excluded: \[1\] corticosteroid nasal spray or inhaler; \[2\] topical corticosteroids for mild, uncomplicated dermatitis; or \[3\] oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur \[length of therapy less than or equal to10 days, with completion in greater than or equal to 30 days prior to enrollment\]).
• History or other clinical evidence of:
• Significant or unstable cardiac or cerebrovascular disease (e.g., angina, congestive heart failure, recent stroke or myocardial infarction).
• Severe illness, malignancy, immunodeficiency other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
• Active drug or alcohol use or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Pregnancy or breast-feeding at time of screening.
• Documented multiclass antiretroviral drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study (Group 1 only).
• Co-enrollment Guidelines: Co-enrollment in other trials is restricted to observational studies or those evaluating the use of a licensed medication and is subject to approval of the principal investigator (PI).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Caskey M, Klein F, Lorenzi JC, Seaman MS, West AP Jr, Buckley N, Kremer G, Nogueira L, Braunschweig M, Scheid JF, Horwitz JA, Shimeliovich I, Ben-Avraham S, Witmer-Pack M, Platten M, Lehmann C, Burke LA, Hawthorne T, Gorelick RJ, Walker BD, Keler T, Gulick RM, Fatkenheuer G, Schlesinger SJ, Nussenzweig MC. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature. 2015 Jun 25;522(7557):487-91. doi: 10.1038/nature14411. Epub 2015 Apr 8.

  PMID: 25855300 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

• Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. doi: 10.1056/NEJMoa1608243. Epub 2016 Nov 9.

  PMID: 27959728 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Limitations and Caveats

The study was terminated early due the the COVID-19 pandemic. The pre-defined samples size of 30 participants (15 per arm) for Group 1 was not not reached prior to closing the protocol.

Results Point of Contact

• Title: Sneller, Michael
• Organization: National Institute of Allergy and Infectious Diseases

msneller@niaid.nih.gov

+1 301 496 0491

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: June 27, 2018
• Study Start: September 10, 2018
• Primary Completion: March 29, 2021
• Study Completion: March 29, 2021
• Last Updated: February 9, 2022
• Results First Posted: February 9, 2022

Record last verified: 2021-03

Locations

US (1)