A Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRCHIVMAB0115-00-AB (VRC01.23LS), Administered Intravenously or Subcutaneously to Healthy Adults

NCT05627258 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 10000889000889-I
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Background: HIV causes AIDS, a serious disease that can lead to fatal infections. HIV infection can be controlled but not cured, nor is there a vaccine to prevent it. Antibodies may offer a promising new way to prevent HIV infection. Antibodies are proteins that are naturally made by the body to fight germs. One antibody (VRC01.23LS) has been tested in the lab and was found to block HIV-like viruses. Researchers want to find out if it is safe to inject VRC01.23LS into people. Objective: To test the safety of VRC01.23LS in healthy adults. Eligibility: Healthy people aged 18 to 60 years. Design: Participants were divided into 6 groups: Some got 1 dose of VRC01.23LS. They visited the clinic up to 14 times in 24 weeks. Some got 3 doses, each 12 weeks apart. They had 25 clinic visits over 48 weeks. For some participants, the drug was given through a tube attached to a needle inserted into a vein in the arm. This took about 30 to 90 minutes. Others received the drug as an injection under the skin in a fatty area of the belly, arm, or thigh; each dose may have needed up to 3 individual injections. Participants stayed in the clinic up to 8 hours on the days they received VRC01.23LS. Participants received a thermometer and measuring tool. They checked their temperature daily for 7 days after they received the study drug. They measured any redness, swelling, or bruising at the injection site.

Conditions

HIV

Keywords

Monoclonal Antibody; CD4 Binding; HIV envelope; First in Human; Broadly Neutralizing

Outcome Measures

Primary Outcomes (6)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration

  Participants recorded the occurrence of solicited local symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)

  7 days after product administration

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Product Administration

  Participants recorded the occurrence of solicited systemic symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017

  7 days after product administration

• Number of Participants With Serious Adverse Events Following Product Administration

  SAEs were recorded from receipt of product administration through the last study visit at Week 24 for participants in Groups 1, 2, 3, 4. SAEs were recorded from receipt of product administration through the last study visit at Week 48 for participants in Groups 5 or 6. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after product administration through Day 168, up to Week 24 for participants in Groups 1-4. Day 0 after product administration through Day 336, up to Week 48, for participants in Group 5 and 6.

• Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration

  Unsolicited AEs and attribution assessments were recorded in the study database from receipt of study product administration through the visit scheduled for 4 weeks after study product administration. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 through 28 days post product administration, up to Week 4

• Number of Participants With New Chronic Medical Conditions Following Product Administration

  New chronic medical conditions that required ongoing medical management were recorded from receipt of study product administration through the last expected study visit at Week 24 for Groups 1-4 and through Week 48 for Groups 5-6. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

  Day 0 after product administration through Day 140, up to Week 24 for Groups 1-4. Day 0 after product administration through Day 336, up to Week 48 for Groups 5-6

• Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration

  Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included pregnancy test, hematology and chemistry labs, and HIV Serology diagnostic test. Institutional lab normal ranges as well as the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 - July 2017 were used.

  Day 0 after product administration through Day 140, up to Week 24 for Groups 1-4. Day 0 after product administration through Day 336, up to Week 48, for Groups 5-6

Secondary Outcomes (5)

• Pharmacokinetic (PK) Parameters of VRC01.23LS: Maximum Observed Serum Concentration (Cmax)

  Baseline through 24 weeks after VRC01.23LS product administration

• Pharmacokinetic (PK) Parameters of VRC01.23LS: Time to Reach Maximum Observed Serum Concentration (Tmax)

  Baseline through 24 weeks after VRC01.23LS product administration

• Pharmacokinetic (PK) Parameters of VRC01.23LS: Beta Half-life (T1/2b)

  Baseline through 24 weeks after VRC01.23LS product administration

• Pharmacokinetic (PK) Parameters of VRC01.23LS: Clearance Rate

  Baseline through 24 weeks after VRC01.23LS product administration

• Pharmacokinetic (PK) Parameters of VRC01.23LS: Volume of Distribution

  Baseline through 24 weeks after VRC01.23LS product administration

Study Arms (6)

Group 1

EXPERIMENTAL

5 mg/kg IV single administration

Biological: VRC-HIVMAB0115-00-AB

Group 2

EXPERIMENTAL

5 mg/kg SC single administration

Biological: VRC-HIVMAB0115-00-AB

Group 3

EXPERIMENTAL

20 mg/kg IV single administration

Biological: VRC-HIVMAB0115-00-AB

Group 4

EXPERIMENTAL

40 mg/kg IV single administration

Biological: VRC-HIVMAB0115-00-AB

Group 5

EXPERIMENTAL

5 mg/kg SC repeat dosing

Biological: VRC-HIVMAB0115-00-AB

Group 6

EXPERIMENTAL

20 mg/kg IV repeat dosing

Biological: VRC-HIVMAB0115-00-AB

Interventions

VRC-HIVMAB0115-00-AB BIOLOGICAL

VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.

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 subject 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 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 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/mm3.
• WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
• Platelets: 125,000 - 500,000/mm3.
• Hemoglobin within institutional normal range or accompanied by PI or designee approval.
• Creatinine: \<= 1.1 x Upper Limit of Normal (ULN).

You may not qualify if:

• A subject 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 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.
• 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 type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, infectious disease, autoimmune disease, psychiatric disorder, heart disease, or cancer.

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)

• Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, Holman LA, Gordon I, Plummer S, Hendel CS, Conan-Cibotti M, Lorenzo MG, Sitar S, Carlton K, Laurencot C, Bailer RT, Narpala S, McDermott AB, Namboodiri AM, Pandey JP, Schwartz RM, Hu Z, Koup RA, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 606 Study Team. Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018 Jan 24;15(1):e1002493. doi: 10.1371/journal.pmed.1002493. eCollection 2018 Jan.

  PMID: 29364886 BACKGROUND

• Gaudinski MR, Houser KV, Doria-Rose NA, Chen GL, Rothwell RSS, Berkowitz N, Costner P, Holman LA, Gordon IJ, Hendel CS, Kaltovich F, Conan-Cibotti M, Gomez Lorenzo M, Carter C, Sitar S, Carlton K, Gall J, Laurencot C, Lin BC, Bailer RT, McDermott AB, Ko SY, Pegu A, Kwon YD, Kwong PD, Namboodiri AM, Pandey JP, Schwartz R, Arnold F, Hu Z, Zhang L, Huang Y, Koup RA, Capparelli EV, Graham BS, Mascola JR, Ledgerwood JE; VRC 605 study team. Safety and pharmacokinetics of broadly neutralising human monoclonal antibody VRC07-523LS in healthy adults: a phase 1 dose-escalation clinical trial. Lancet HIV. 2019 Oct;6(10):e667-e679. doi: 10.1016/S2352-3018(19)30181-X. Epub 2019 Aug 28.

  PMID: 31473167 BACKGROUND

• Kwon YD, Asokan M, Gorman J, Zhang B, Liu Q, Louder MK, Lin BC, McKee K, Pegu A, Verardi R, Yang ES, Program VP, Carlton K, Doria-Rose NA, Lusso P, Mascola JR, Kwong PD. A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention. MAbs. 2021 Jan-Dec;13(1):1946918. doi: 10.1080/19420862.2021.1946918.

  PMID: 34328065 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: Lesia K. Dropulic, M.D./Principal Investigator; Laura Novik, R.N., M.A./Study Coordinator
• Organization: Vaccine Research Center Clinical Trials Program, NIAID

lesia.dropulic@nih.gov; laura.novik@nih.gov

301-451-8717

Study Officials

• Lesia K Dropulic, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2022
• First Posted: November 25, 2022
• Study Start: January 30, 2023
• Primary Completion: July 17, 2024
• Study Completion: July 17, 2024
• Last Updated: August 22, 2025
• Results First Posted: August 22, 2025

Record last verified: 2024-09-18

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)