3BNC117-LS First-in-Human Phase 1 Study

NCT03254277 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: YCO-0946
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a phase 1 study of the mAb 3BNC117-LS administered intravenously in HIV uninfected individuals and HIV-infected individuals, and subcutaneously in HIV-uninfected individuals.The objectives of the study are to evaluate the safety, tolerability and pharmacokinetics of a single administration of 3BNC117-LS.

Conditions

Human Immunodeficiency Virus

Keywords

Broadly Neutralizing Antibody; 3BNC117-LS; First in Human; Dose Escalation

Outcome Measures

Primary Outcomes (6)

• The number of participants who experience adverse events within 2 weeks after 3BNC117-LS infusion in all study groups

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

  2 weeks following the 3BNC117-LS infusion

• Elimination half-life (t1/2) of 3BNC117-LS in all study groups

  Elimination half-life (t1/2) of 3BNC117-LS in all study groups

  48 weeks

• Clearance (CL/F) of 3BNC117-LS in all study groups

  Clearance (CL/F) of 3BNC117-LS in all study groups

  48 weeks

• Volume of distribution (Vz/F) of 3BNC117-LS in all study groups

  Volume of distribution (Vz/F) of 3BNC117-LS in all study groups

  48 weeks

• Area under the curve of 3BNC117-LS in all study groups

  Area under the curve of 3BNC117-LS in all study groups

  48 weeks

• Decay curve of 3BNC117-LS in all study groups

  Decay curve of 3BNC117-LS in all study groups

  48 weeks

Secondary Outcomes (3)

• Frequency of induced anti-3BNC117-LS antibodies in all study groups.

  48 weeks

• Levels of induced anti-3BNC117-LS antibodies in all study groups.

  48 weeks

• The number of participants who experience adverse events during study follow-up

  48 weeks

Other Outcomes (7)

• 3BNC117-LS levels in cervicovaginal and rectal fluids

  Day 0 and 2 weeks following 3BNC117-LS infusion

• The decline in plasma HIV-1 RNA level after 3BNC117-LS infusion in viremic HIV-infected individuals

  48 weeks

• Analysis of escape viruses in individuals not on ART

  48 weeks

Study Arms (9)

Group 1A

EXPERIMENTAL

HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 3 mg/kg.

Drug: 3BNC117-LS

Group 1B

EXPERIMENTAL

HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.

Drug: 3BNC117-LS

Group 1C

EXPERIMENTAL

HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

Drug: 3BNC117-LS

Group 2B

EXPERIMENTAL

HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 20 copies/ml or off ART for at least 8 weeks with HIV-1 plasma RNA levels \< 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 10 mg/kg.

Drug: 3BNC117-LS

Group 2C

EXPERIMENTAL

HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 20 copies/ml, or off ART for at least 8 weeks with HIV-1 plasma RNA levels \< 100,000 copies/ml, will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

Drug: 3BNC117-LS

Group 1D

EXPERIMENTAL

HIV-uninfected individuals will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

Drug: 3BNC117-LS

Group 2D

EXPERIMENTAL

HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 20 copies/ml will be administered one infusion of 3BNC117-LS dosed at 30 mg/kg.

Drug: 3BNC117-LS

Group 1E

EXPERIMENTAL

HIV-uninfected individuals will be administered a single 1 mL (approximately 150 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

Drug: 3BNC117-LS; Drug: Placebo

Group 1F

EXPERIMENTAL

HIV-uninfected individuals will be administered a single 2 mL (approximately 300 mg) subcutaneous injection of 3BNC117-LS or placebo in a 3:1 ratio.

Drug: 3BNC117-LS; Drug: Placebo

Interventions

3BNC117-LS DRUG

Intravenous infusion of 3BNC117-LS

Also known as: Monoclonal Antibody

Group 1A; Group 1B; Group 1C; Group 1D; Group 1E; Group 1F; Group 2B; Group 2C; Group 2D

Placebo DRUG

Placebo

Group 1E; Group 1F

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Groups 1A-1F (HIV-uninfected):
• Males and females, age 18 to 65
• Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
• 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 IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.
• Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.
• Groups 2B-2D (HIV-infected):
• Males and females, age 18 to 65.
• HIV-1 infection confirmed by two laboratory assays.
• HIV-infected individuals off ART for at least 8 weeks with HIV-1 plasma RNA levels \< 100,000 copies/ml by standard assays (ART-naïve or off ART due to intolerance or by choice), or on ART with HIV-1 plasma RNA levels \< 20 copies/ml. HIV-1 RNA levels should be measured on 2 occasions, at least 1 week apart. At least one measurement must be performed within 49 days prior to enrollment (day 0). Group 2D will only enroll HIV-infected individuals on ART.
• Current CD4+ T cell count \> 300 cells/μl.
• If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and until seven months after 3BNC117-LS infusion, and agrees to safer sex counseling at each visit.

You may not qualify if:

• Groups 1A-1F (HIV-uninfected):
• Confirmed HIV-1 or HIV-2 infection.
• History of immunodeficiency or autoimmune disease; use 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) that in the opinion of the investigator would preclude participation.
• Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
• 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.
• Laboratory abnormalities in the parameters listed:
• Absolute neutrophil count ≤ 1,500 cells/µL;
• Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;
• Platelet count ≤ 125,000 cells/µL;
• Alanine transaminase (ALT) ≥ 1.25 x ULN;
• Aspartate transaminase (AST) ≥ 1.25 x ULN;
• Alkaline phosphatase ≥ 1.5 x ULN;
• Total bilirubin \> 1 x ULN;
• Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2.

Sponsors & Collaborators

• Rockefeller University: lead

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (1)

• Valente PK, Wu Y, Cohen YZ, Caskey M, Meyers K. Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention. Clin Trials. 2021 Feb;18(1):17-27. doi: 10.1177/1740774520948042. Epub 2020 Aug 24.

  PMID: 32838558 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

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

  The Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 18, 2017
• Study Start: September 13, 2017
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: February 3, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)