3BNC117 and 10-1074 in HIV-infected Individuals

NCT02825797 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MCA-0906
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase 1b clinical trial to evaluate the safety, pharmacokinetics and the antiretroviral effects of the combination of two anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies, 3BNC117 and 10-1074, administered intravenously in HIV-infected individuals. This study is intended to support the development of the combination of 3BNC117 and 10-1074 mAbs for use in the treatment of HIV-1 infection.

Conditions

Human Immunodeficiency Virus (HIV)

Keywords

Broadly neutralizing antibody; 3BNC117; 10-1074

Outcome Measures

Primary Outcomes (4)

• The number of participants with adverse events 1 week after 3BNC117 and 10-1074 infusions in all study groups.

  Adverse events include: signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity

  1 week following each combination of 3BNC117 and 10-1074 infusion

• The decline in plasma HIV-1 RNA levels by a standard clinical assay in participants off ART enrolled in groups 1C and 3.

  20-24 weeks

• The percentage of participants who meet ART re-initiation criteria (plasma HIV-1 RNA ≥ 200 copies/ml and/or CD4 count < 350 cells/μl on two consecutive measurements) prior to 8 weeks after ART interruption in group 2.

  30 weeks

• Time to meeting ART re-initiation criteria (plasma HIV-1 RNA level ≥ 200 copies/ml, CD4+ T cell count < 350 cells/l in 2 consecutive measurements) following ART interruption in group 2.

  30 weeks

Secondary Outcomes (5)

• The number of participants with adverse events that occur during study follow up after 3BNC117 and 10-1074 infusions in all study groups.

  20-30 weeks

• The serum level of 3BNC117 and 10-1074 at the time of viral rebound in all study groups.

  20-30 weeks

• Number of participants with induced anti-3BNC117 and anti-10-1074 antibodies.

  20-30 weeks

• Level of induced anti-3BNC117 and anti-10-1074 antibodies.

  20-30 weeks

• Change in number of CD4+ T cells/uL

  20-30 weeks

Other Outcomes (10)

• Changes in viral envelope sequences following 3BNC117 and 10-1074 infusions (groups 1C, 2-3)

  20-30 weeks

• Phylogenetic comparison of viruses grown from PBMCs collected from subjects while on ART to rebound viruses collected after treatment interruption (group 2).

  20-30 weeks

• Levels of cell-associated HIV-1 RNA and DNA before and after 3BNC117 and 10-1074 infusions in HIV-infected individuals.

  20-30 weeks

Study Arms (5)

Group 1A

EXPERIMENTAL

HIV-infected individuals, on ART with HIV-1 RNA \< 20 copies/ml will be randomized in a 2:1 ratio to receive one intravenous infusion of 3BNC117 and one intravenous infusion of 10-1074), each dosed at 10 mg/kg OR placebo (sterile saline), on day 0.

Drug: 3BNC117; Drug: 10-1074; Drug: Placebo

Group 1B

EXPERIMENTAL

HIV-infected individuals, on ART with HIV-1 RNA \< 20 copies/ml will be randomized in a 2:1 ratio to receive one intravenous infusion of 3BNC117 and one intravenous infusion 10-1074, each dosed at 30 mg/kg, OR placebo (sterile saline), on day 0.

Drug: 3BNC117; Drug: 10-1074; Drug: Placebo

Group 1C

EXPERIMENTAL

HIV-infected individuals, off ART will be administered one infusion of 3BNC117 and one infusion 10-1074, each dosed at 30 mg/kg, on day 0.

Drug: 3BNC117; Drug: 10-1074

Group 2

EXPERIMENTAL

HIV-infected individuals, on ART with HIV-1 RNA \< 20 copies/ml will be administered three infusions of 3BNC117 and three infusions of 10-1074, each dosed at 30 mg/kg, on days 0, 21 and 42. Participants enrolled in Group 2 will undergo an analytical treatment interruption and they will discontinue their antiretroviral (ART) regimen on day 2.

Drug: 3BNC117; Drug: 10-1074; Other: Analytical treatment interruption

Group 3

EXPERIMENTAL

HIV-infected individuals, off ART who will be administered three infusions of 3BNC117 and three infusions of 10-1074, each dosed at 30 mg/kg on days 0, 14 and 28.

Drug: 3BNC117; Drug: 10-1074

Interventions

3BNC117 DRUG

Intravenous infusion of 3BNC117

Also known as: Monoclonal Antibody

Group 1A; Group 1B; Group 1C; Group 2; Group 3

10-1074 DRUG

Intravenous infusion of 10-1074

Also known as: Monoclonal Antibody

Group 1A; Group 1B; Group 1C; Group 2; Group 3

Analytical treatment interruption OTHER

Analytical treatment interruption

Also known as: ART interruption

Group 2

Placebo DRUG

Intravenous infusion of placebo (sterile saline)

Also known as: Sterile Saline

Group 1A; Group 1B

Eligibility Criteria

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

You may qualify if:

• All groups:
• Age 18 to 65.
• HIV-1 infection confirmed by two independent laboratory assays.
• If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting intrauterine device (IUD), hormone-based contraceptive with condom) for the study duration.
• Groups 1A and 1B:
• HIV-infected volunteers on ART with HIV-1 plasma RNA levels \< 20 copies/ml.
• Current CD4 cell count \> 300 cells/μl.
• Groups 1C and 3:
• HIV-infected volunteers off ART with detectable HIV-1 plasma RNA levels \< 100,000 copies/ml by standard assays.
• Current CD4 cell count \> 300 cells/μl.
• Group 2:
• On antiretroviral therapy for a minimum of 24 months, with plasma HIV-1 RNA levels of \< 50 copies/ml for at least 18 months, and \< 20 copies/ml at screening. Note: a single viral load measurement \> 50 but \< 500 copies/ml during this time period is allowed.
• Current CD4+ T cell counts \> 500 cells/μl. CD4 cell count nadir \> 200 cells/μl.
• If on an NNRTI-based regimen willing to switch to a dolutegravir-based regimen for 4 weeks prior to discontinuing ART.

You may not qualify if:

• Have a history of AIDS-defining illness within 3 year prior to enrollment.
• History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
• Any clinically significant acute or chronic medical condition (such as autoimmune diseases or coronary artery disease), other than HIV infection, that in the opinion of the investigator would preclude participation.
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
• History of resistance to 2 or more classes of antiretroviral medication or known resistance to dolutegravir in participants on non-nucleoside reverse-transcriptase inhibitors (NNRTI), who would switch regimen prior to ATI (Group 2).
• Laboratory abnormalities in the parameters listed below:
• Absolute neutrophil count ≤ 1,000 cells/l
• Hemoglobin ≤ 10 gm/dL
• Platelet count ≤ 100,000 cells/l
• Alanine Aminotransferase (AST) ≥ 1.5 x ULN
• Aspartate Aminotransferase (AST) ≥ 1.5 x ULN
• Alkaline phosphatase ≥ 1.5 x ULN
• Total bilirubin \> 1.0 ULN
• eGFR \< 60 mL/min/1.73m2
• Pregnancy or lactation;

Sponsors & Collaborators

• Rockefeller University: lead
• University Hospital of Cologne: collaborator

Study Sites (2)

The Rockefeller University

New York, New York, 10065, United States

Location

University Hospital of Cologne

Cologne, Germany

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

3BNC117 antibody; Antibodies, Monoclonal

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

Study Officials

• Marina Caskey, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: July 7, 2016
• Study Start: June 1, 2016
• Primary Completion: August 1, 2018
• Study Completion: August 15, 2018
• Last Updated: August 21, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); DE (1)