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

VRC 615: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB-0115-AB (VRC01.23LS), Administered Intravenously or Subcutaneously to Healthy Adults

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Biological: VRC-HIVMAB0115-00-AB

Detailed Description

Study Design:

This first-in-human, open-label study evaluated VRC01.23LS (VRCHIVMAB0115- 00-AB) in a dose-escalation design to examine safety, tolerability, dose, and pharmacokinetics (PK) in healthy adults. The primary hypothesis was that subcutaneous (SC) and intravenous (IV) administrations of VRC01.23LS will be safe and well-tolerated in healthy adults. A secondary hypothesis was that VRC01.23LS will be detectable in human sera with a definable half-life.

Study Products:

The VRC01.23LS broadly neutralizing monoclonal antibody (bnAb) targets the CD4 binding site in the HIV-1 envelope, is human in origin, and contains two amino acid modifications within the C-terminus of the heavy chain constant region designed to improve the antibody half-life in vivo. VRC01.23LS was developed by the VRC/NIAID/NIH and manufactured under cGMP regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick. MD.

Subjects:

Healthy adults, 18-60 years of age

Study Plan:

This open-label study included 6 groups to evaluate VRC01.23LS administered as a single dose or as repeated doses, given 12 weeks apart as shown in the table below. Enrollment began with the 5 mg/kg dose groups, and enrollment in subsequent dose groups proceeded after dose-escalation safety reviews. Assessment of safety included solicited reactogenicity, clinical observation, and monitoring of hematological and metabolic parameters at clinical visits throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

A subject must meet all of the following criteria:

1. Willing and able to complete the informed consent process.
2. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
3. Available for clinical follow-up through the last study visit.
4. 18 to 60 years of age.
5. In good general health without clinically significant medical history.
6. Physical examination without clinically significant findings within the 56 days prior to enrollment.
7. Adequate venous access if assigned to an IV group or adequate abdominal subcutaneous tissue if assigned to SC group.

8. Willing to have blood samples collected, stored indefinitely, and used for research purposes.

   Laboratory Criteria within 56 days prior to enrollment:

9. White blood cell count (WBC): 2,500-12,000/mm3.
10. WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
11. Platelets: 125,000 - 500,000/mm3.
12. Hemoglobin within institutional normal range or accompanied by PI or designee approval.
13. Creatinine: <= 1.1 x Upper Limit of Normal (ULN).
14. ALT: <= 1.25 x ULN.
15. AST: <= 1.25 x ULN.

16. Negative for HIV infection by an FDA approved method of detection.

    Female-Specific Criteria:

17. Agrees to use an effective means of birth control from 21 days prior to enrollment through the duration of study participation.
18. Negative Beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.

EXCLUSION CRITERIA:

A subject will be excluded if one or more of the following conditions apply:

1. Woman who is breast-feeding or planning to become pregnant during study participation.
2. Weight > 115 kg.
3. 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.
4. Hypertension that is not well controlled.
5. Receipt of any investigational study product within 28 days prior to enrollment (Note: Emergency Use Authorization of a COVID-19 vaccine is not exclusionary).
6. Receipt of an investigational HIV vaccine or anti-HIV monoclonal antibody.
7. Receipt of any live attenuated vaccine within 28 days prior to enrollment.
8. Receipt of any vaccine within 2 weeks prior to enrollment.
9. 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.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 5 mg/kg IV single administration	Biological: VRC-HIVMAB0115-00-AB; VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.
Experimental: Group 2; 5 mg/kg SC single administration	Biological: VRC-HIVMAB0115-00-AB; VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.
Experimental: Group 3; 20 mg/kg IV single administration	Biological: VRC-HIVMAB0115-00-AB; VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.
Experimental: Group 4; 40 mg/kg IV single administration	Biological: VRC-HIVMAB0115-00-AB; VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.
Experimental: Group 5; 5 mg/kg SC repeat dosing	Biological: VRC-HIVMAB0115-00-AB; VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.
Experimental: Group 6; 20 mg/kg IV repeat dosing	Biological: VRC-HIVMAB0115-00-AB; VRC01.23LS, a broadly neutralizing monoclonal antibody targeting the HIV-1 envelope CD4 binding site.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameters of VRC01.23LS: Maximum Observed Serum Concentration (Cmax)	Cmax is the peak serum concentration that VRC01.23LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.	Baseline through 24 weeks after VRC01.23LS product administration
Pharmacokinetic (PK) Parameters of VRC01.23LS: Time to Reach Maximum Observed Serum Concentration (Tmax)	Tmax is the time it takes to reach Cmax of VRC01.23LS after it has been administered; it is determined based on the summary PK curve for each dose group.	Baseline through 24 weeks after VRC01.23LS product administration
Pharmacokinetic (PK) Parameters of VRC01.23LS: Beta Half-life (T1/2b)	Beta half-life (T1/2b) is the time required for half of the VRC01.23LS product to be eliminated from the serum.	Baseline through 24 weeks after VRC01.23LS product administration
Pharmacokinetic (PK) Parameters of VRC01.23LS: Clearance Rate	Clearance is the rate of VRC01.23LS elimination divided by the plasma VRC01.23LS concentration; determined based on the summary pharmacokinetic (PK) curve for each study group. Clearance following a SC administration is calculated as Clearance (CL)/Bioavailability (F).	Baseline through 24 weeks after VRC01.23LS product administration
Pharmacokinetic (PK) Parameters of VRC01.23LS: Volume of Distribution	Theoretical volume that would be necessary to contain the total amount of administered drug at the same concentration as observed in plasma. It represents the degree to which a drug is distributed in body tissue rather than the plasma and calculated based in the PK curve for each study group. Volume of distribution following a SC administration is calculated as Volume of distribution (V)/Bioavailability (F).	Baseline through 24 weeks after VRC01.23LS product administration

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Lesia K Dropulic, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Actual): July 17, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: November 23, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: September 18, 2024

More Information

Terms related to this study

• Keywords: Monoclonal Antibody; First in Human; Broadly Neutralizing; CD4 Binding; HIV envelope
• Other Study ID Numbers: 10000889; 000889-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Please refer to protocol Section 9.3.4.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No