First-in-human Study of 10-1074-LS Alone and in Combination With 3BNC117-LS

NCT03554408 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: YCO-0971
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This first clinical study of 10-1074-LS will evaluate its safety, tolerability and pharmacokinetics profile when administered alone or in combination with 3BNC117-LS to HIV (human immunodeficiency virus) -infected and HIV-uninfected individuals.

Conditions

Human Immunodeficiency Virus

Keywords

10-1074-LS; 3BNC117-LS; First in Human; Dose Escalation

Outcome Measures

Primary Outcomes (7)

• The number of participants who experience adverse events within 2 weeks after 10-1074-LS intravenous infusions and subcutaneous injections.

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

  2 weeks

• The number of participants who experience adverse events within 2 weeks after 10-1074-LS and 3BNC117-LS intravenous infusions and subcutaneous injections.

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

  2 weeks

• Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  48-72 weeks

• The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  48-72 weeks

• The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups

  The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups

  48-72 weeks

• Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  48-72 weeks

• Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

  48-72 weeks

Secondary Outcomes (5)

• Frequency of induced anti-10-1074-LS antibodies

  48-72 weeks

• Level of induced anti-10-1074-LS antibodies

  48-72 weeks

• Frequency of induced anti-3BNC117-LS antibodies

  48-72 weeks

• Level of induced anti-3BNC117-LS antibodies

  48-72 weeks

• The number of participants that experience who experience adverse events during the study follow up period after 10-1074-LS and/or 3BNC117-LS administration in all study groups.

  48-72 weeks

Study Arms (14)

Group 1A

EXPERIMENTAL

HIV-uninfected individuals will be administered one 1 mL (approximately 150 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.

Drug: 10-1074-LS

Group 1B

EXPERIMENTAL

HIV-uninfected individuals will be administered one 2 mL (approximately 300 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.

Drug: 10-1074-LS

Group 2A

EXPERIMENTAL

HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 3 mg/kg.

Drug: 10-1074-LS

Group 2B

EXPERIMENTAL

HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.

Drug: 10-1074-LS

Group 2C

EXPERIMENTAL

HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.

Drug: 10-1074-LS

Group 3B

EXPERIMENTAL

HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg

Drug: 10-1074-LS

Group 3C

EXPERIMENTAL

HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.

Drug: 10-1074-LS

Group 4A

EXPERIMENTAL

HIV-uninfected individuals will be administered one 2 mL (approximately 150 mg of each mAb) subcutaneous injection of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.

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

Group 4B

EXPERIMENTAL

HIV-uninfected individuals will be administered two 2 mL (approximately 300 mg of each mAb) subcutaneous injections of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.

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

Group 5

EXPERIMENTAL

HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.

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

Group 6

EXPERIMENTAL

HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.

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

Group 7

EXPERIMENTAL

HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (100 mg) admixed with 3BNC117-LS (200 mg) (2 mL) at weeks 0, 12, and 24.

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

Group 8

EXPERIMENTAL

HIV-infected individuals (on ART) will be administered three subcutaneous injections of 10-1074-LS (75 mg) admixed with 3BNC117-LS (225 mg) (2 mL) at weeks 0, 12, and 24.

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

Group 9

EXPERIMENTAL

HIV-infected individuals (on ART) will be administered three subcutaneous injections of 10-1074-LS (60 mg) admixed with 3BNC117-LS (250 mg) (2 mL) at weeks 0, 12, and 24.

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

Interventions

10-1074-LS DRUG

Subcutaneous injection of 10-1074-LS

Also known as: Monoclonal antibody

Group 1A; Group 1B; Group 4A; Group 4B; Group 7; Group 8; Group 9

3BNC117-LS DRUG

Subcutaneous injection of 3BNC117-LS

Also known as: Monoclonal antibody

Group 4A; Group 4B; Group 7; Group 8; Group 9

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-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (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 nine months after 10-1074-LS and/or 3BNC117-LS administration.
• \- 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 3B-3C, 6 (HIV-infected):
• Males and females, age 18 to 65.
• Confirmed HIV-1 infection.
• HIV-infected individuals on ART with HIV-1 plasma RNA levels \< 50 copies/mL.
• 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 nine months after 10-1074-LS and/or 3BNC117-LS administration.

You may not qualify if:

• Groups 1A-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (HIV-uninfected):
• Confirmed HIV-1 or HIV-2 infection.
• Weight \> 110 kg (subcutaneous groups only: 1A-1B, 4A-4B).
• History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant
• 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;
• ALT ≥ 1.25 x ULN;
• AST ≥ 1.25 x ULN;
• Alkaline phosphatase ≥ 1.5 x ULN;by the trial physician within the last 6 months.
• Pregnancy or lactation.

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Groups 1A, 1B, 4A, and 4B are double-blinded; All other arms are open label.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: June 13, 2018
• Study Start: June 20, 2018
• Primary Completion: February 4, 2021
• Study Completion: February 4, 2021
• Last Updated: August 4, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)