Study of a Human Bispecific Antibody VRC-HIVMAB0121-00-AB (CAP256J3LS) Administered Intravenously or Subcutaneously to Healthy Adults

NCT06585891 | Completed Phase 1 FDA Drug

• 2 other identifiers: 10001965001965-I
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Background: HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immunodeficiency syndrome). Researchers want to find new ways to treat or prevent HIV infection. CAP256J3LS is a new product that uses antibodies. Antibodies are naturally occurring proteins; they target and disable disease-causing agents such as viruses. This new product may be able to stop HIV infections. Objective: To test the safety of CAP256J3LS in healthy people. Eligibility: People aged 18 to 60 years in good general health. Design: CAP256J3LS can be administered in 2 ways: (1) by a shot under the skin into the belly fat or (2) through a tube inserted into a vein in the arm. Participants will be divided into 6 groups: The study will open with the lowest dose of study product. The dose groups are spaced out to allow the study team to look over the safety data in each group. If there are no safety concerns in the lowest dose, then the next higher dose groups will be enrolled. This pattern will continue until all dose groups are enrolled.. Also, some participants will receive only 1 dose; others will receive 3 doses, each spaced 12 weeks apart. Those who receive only 1 dose of the study drug will have 14 clinic visits over 6 months. Those who get 3 doses will have 27 visits over 11 months. Participants will provide blood samples at each visit. Urine samples may also be needed. All participants will get a thermometer and a measuring tool. They will measure any redness, swelling, or bruising they have at the injection site. They will check their temperature every day for 7 days after receiving the study drug. They will record their highest temperatures and any symptoms they have. ...

Conditions

HIV Infection

Keywords

Immune Response; HIV; Bi-Specific Antibody

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of CAP256J3LS (5 mg/kg SC) administered to healthy adults

  To evaluate the safety and tolerability of a single SC dose

  Through 24 weeks after product administration

• Safety and tolerability of CAP256J3LS ( 5mg/kg or 20mg/kg or 40 mg/kg IV) administered to healthy adults

  To evaluate the safety and tolerability of a single IV dose

  Through 24 weeks after product administration

• Safety and tolerability of CAP256J3LS ( 5 mg/kg SC) administered for for a total of 3 injections in 12 week intervals to healthy adults

  To evaluate the safety and tolerability of a repeat SC dosing

  Through 24 weeks after last product administration

• Safety and tolerability of CAP256J3LS ( 20 mg/kg IV) administered for for a total of 3 injections in 12 week intervals to healthy adults

  To evaluate the safety and tolerability of a repeat IV dosing

  Through 24 weeks after last product administration

Secondary Outcomes (1)

• PK will be evaluated at each dose level and route of administration

  Throughout the study

Study Arms (6)

Group 1

EXPERIMENTAL

5 mg/kg IV- single administration

Biological: VRC-HIVMAB0121-00-AB

Group 2

EXPERIMENTAL

5 mg/kg SC- single administration

Biological: VRC-HIVMAB0121-00-AB

Group 3

EXPERIMENTAL

20 mg/kg IV- single administration

Biological: VRC-HIVMAB0121-00-AB

Group 4

EXPERIMENTAL

40 mg/kg IV- single administration

Biological: VRC-HIVMAB0121-00-AB

Group 5

EXPERIMENTAL

5 mg/kg SC- repeat dosing

Biological: VRC-HIVMAB0121-00-AB

Group 6

EXPERIMENTAL

20 mg/kg IV-repeat dosing

Biological: VRC-HIVMAB0121-00-AB

Interventions

VRC-HIVMAB0121-00-AB BIOLOGICAL

The CAP256J3LS bispecific antibody (bsAbs) targets the V2-apex and CD4-binding sites of the HIV-1 envelope. It is composed of the light chain of CAP256V2LS, linked to the llama nanobody J3, which has broad CD4-binding site-directed neutralization.

Group 1; Group 2; Group 3; Group 4; Group 5; Group 6

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A participant must meet all of the following criteria:
• Willing and able to complete the informed consent process.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Available for clinical follow-up through the last study visit.
• to 60 years of age.
• In good general health without a clinically significant medical history.
• Physical examination without clinically significant findings within the 56 days prior to enrollment.
• Adequate venous access if assigned to an IV group or adequate abdominal subcutaneous tissue if assigned to a SC group.
• Willing to have blood samples collected, stored indefinitely, and used for research purposes.
• Laboratory Criteria within 56 days prior to enrollment:
• White blood cell count (WBC): 2,500-12,000/mm\^3.
• WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval, excluding absolute lymphocyte count which must not be lower than normal range.
• Platelets: 125,000 - 400,000/mm\^3.
• Hemoglobin within institutional normal range or is lower than normal range but does not meet Grade 1 criteria and is not clinically concerning.
• Creatinine: \<= 1.1 x Upper Limit of Normal (ULN).

You may not qualify if:

• A participant will be excluded if one or more of the following conditions apply:
• Woman who is breast-feeding or planning to become pregnant during study participation.
• Weight \> 115 kg.
• Any history of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis prior to enrollment that has a reasonable risk of recurrence during the study.
• Hypertension that is not well controlled.
• Receipt of any investigational study product within 28 days prior to enrollment.
• Receipt of an investigational HIV vaccine or anti-HIV monoclonal antibody.
• Receipt of any live attenuated vaccine within 28 days prior to enrollment.
• Receipt of any vaccine within 2 weeks prior to enrollment.
• Known history of Gilbert's syndrome.
• Known history of kidney or liver disease.
• Diabetes mellitus (type I or II), with the exception of a history of gestational diabetes.
• More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within 14 days prior to enrollment.
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
• Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer, including but not limited to diabetes mellitus, hepatitis, asthma, infectious disease, autoimmune disease, psychiatric disorder, heart disease, cancer and clinically significant forms of drug or alcohol abuse.

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 (2)

• Zhang B, Gorman J, Kwon YD, Pegu A, Chao CW, Liu T, Asokan M, Bender MF, Bylund T, Damron L, Gollapudi D, Lei P, Li Y, Liu C, Louder MK, McKee K, Olia AS, Rawi R, Schon A, Wang S, Yang ES, Yang Y, Carlton K, Doria-Rose NA, Shapiro L, Seaman MS, Mascola JR, Kwong PD. Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency. MAbs. 2023 Jan-Dec;15(1):2165390. doi: 10.1080/19420862.2023.2165390.

  PMID: 36729903 BACKGROUND

• McCoy LE, Quigley AF, Strokappe NM, Bulmer-Thomas B, Seaman MS, Mortier D, Rutten L, Chander N, Edwards CJ, Ketteler R, Davis D, Verrips T, Weiss RA. Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization. J Exp Med. 2012 Jun 4;209(6):1091-103. doi: 10.1084/jem.20112655. Epub 2012 May 28.

  PMID: 22641382 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Lasonji A Holman, C.R.N.P.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 5, 2024
• First Posted: September 19, 2024
• Study Start: October 7, 2024
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: March 23, 2026

Record last verified: 2026-03-19

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)