Phase 1, Open-label, Single Dose Study to Examine Safety, Tolerability, Pharmacokinetics and Virologic Impact of VRC01LS or VRC07-523LS in HIV-infected Viremic Adults

NCT02840474 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 16014716-I-014730089
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 7

Brief Summary

Background: The human body uses antibodies as one way to help fight infection. VRC01LS and VRC07-523LS are antibodies directed against the HIV virus. Researchers want to see if they are safe and well tolerated. In Part A of the study, the researchers studied VRC01LS. Part A of the study was completed in 2017. In Part B, the researchers studied VRC07-523LS. Depending on which antibody received, researchers studied the amount of VRC01LS or VRC07-523LS in the body and how it changes over time. They evaluated the effect of antibodies on CD4+ (Cluster of Differentiation 4) lymphocyte count and HIV viral load, and checked to see if people who get VRC01LS or VRC07-523LS develop an immune response to it. Objective: To see if VRC01LS and VRC07-523LS are safe and well tolerated. Eligibility: Adults ages 18-70 who are HIV infected but otherwise healthy. Design: Participants received the study drug one time by IV infusion. A needle guided a thin tube into a vein. The study drug mixed with salt water was dripped into the vein over about 30 minutes. Participants were monitored for 30 minutes after the infusion. Blood samples were taken at the following times:

• Once before the infusion
• 5 times in the 4 hours after the infusion
• 1 time 24 hours after infusion. Some participants may have had 3 optional blood draws in the time period between 4 and 24 hours. For 3 days after the infusion, participants recorded their temperature and reactogenicity symptoms in a diary. There were a total of 23 study visits over 48 weeks. Ten visits were in the first 4 weeks. At all visits, participants answered health questions and gave blood samples.

Conditions

HIV-1

Keywords

HIV Viral Load; Antiviral; CD4 Count; HIV-1 Infection; Broadly Neutralizing Antibody

Outcome Measures

Primary Outcomes (5)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 3 Days After VRC01LS or VRC07-523LS Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 3 days after the 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 U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\].

  3 days after study product administration

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms for 3 Days After VRC01LS or VRC07-523LS Administration

  Participants recorded the occurrence of solicited symptoms on a diary card for 3 days after the 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 U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\].

  3 days after study product administration

• Number of Participants With Abnormal Laboratory Measures of Safety

  Any abnormal laboratory results recorded as unsolicited AEs are summarized. Labs included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV), platelets, white blood cell (WBC) and red blood cell (RBC) counts, and neutrophil, lymphocyte, monocyte, eosinophil and basophil percents and counts) and chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and creatinine). Complete blood count (CBC) and platelet results were collected at screening, Day 0 prior to study product administration (baseline), and Days 2 and 7, Weeks 2-8, 12, 16, 20, 24, 36 and 48 after product administration. Creatinine, ALT, AST and ALP results were collected at screening, baseline, and Days 2 and 7, Weeks 2, 4, 12, 24, 36 and 48 after product administration. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 \[November 2014\] were used.

  Through 48 weeks after study product administration

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

  Unsolicited AEs and attribution assessments were recorded in the study database from receipt of the study product administration through the visit scheduled for 56 days (or 8 weeks) after study product administration. At other time periods greater than 56 days (or 8 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 that required ongoing medical management 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.

  Through 56 days after study product administration

• Number of Participants With Serious Adverse Events (SAEs)

  SAEs were recorded from receipt of the study product administration through the last expected study visit at Week 48. The relationship between a SAE and the study product was assessed by the investigator on the basis of his or her 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.

  Through 48 weeks after study product administration

Secondary Outcomes (11)

• Area Under the Curve For the Last Study Visit (AUC(Last))

  Administration (0h) to 48 weeks after study product administration

• Clearance Rate of VRC01LS or VRC07-523LS Administered at 40 mg/kg IV

  Administration (0h) to 48 weeks after study product administration

• Maximum Observed Serum Concentration (Cmax) of VRC01LS or VRC07-523LS Administered at 40 mg/kg IV

  Through 48 weeks after study product administration

• Half-life (T1/2) of VRC01LS or VRC07-523LS Administered at 40 mg/kg IV

  Through 48 weeks after study product administration

• Mean Serum Concentration of VRC01LS or VRC07-523LS Administered at 40 mg/kg IV

  Day 28 and Day 84 after study product administration

Study Arms (2)

Part A: VRC01LS (40 mg/kg)

EXPERIMENTAL

VRC-HIVMAB080-00-AB (VRC01LS) - (40 mg/kg) - administered intravenously (IV) at Day 0

Biological: VRC-HIVMAB080-00-AB

Part B: VRC07-523LS (40 mg/kg)

EXPERIMENTAL

VRC-HIVMAB075-00-AB (VRC07-523LS) - (40 mg/kg) - administered IV at Day 0

Biological: VRC-HIVMAB075-00-AB

Interventions

VRC-HIVMAB080-00-AB BIOLOGICAL

VRC01LS is an investigational human monoclonal antibody targeted to the CD4+ binding site of HIV-1.

Also known as: VRC01LS

Part A: VRC01LS (40 mg/kg)

VRC-HIVMAB075-00-AB BIOLOGICAL

VRC07-523LS is an investigational human monoclonal antibody targeted to the CD4+ binding site of HIV-1.

Also known as: VRC07-523LS

Part B: VRC07-523LS (40 mg/kg)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A participant must meet all of the following criteria:
• Able and willing to complete the informed consent process.
• years old
• Available for clinic visits for 48 weeks after study product administration.
• HIV-1 infected and clinically stable. \[Note: Documented HIV-1 infection by HIV enzyme immunoassay (EIA) performed by a Clinical Laboratory Improvement Amendments (CLIA) certified outside lab within 28 days of enrollment is acceptable.\]
• At least one plasma viral load \>=500 copies/mL within 28 days of enrollment. A plasma viral load within 28 days and closest to the day of enrollment, that is detectable but not greater than 100,000 copies/mL. \[Note: outside laboratory results will be acceptable\].
• A CD4+ count \>=350 cells/microliter (mcL) on 2 of 3 consecutive testing occasions (or on 2 of 2 sequential tests) within 28 days prior to enrollment. \[Note: outside laboratory results will be acceptable\].
• In general good health as assessed by a study clinician and under the care of a primary health care provider for medical management of HIV infection while participating in the study. Willing to give consent to contact and send laboratory results to the participant's primary health provider.
• Willing to have blood samples collected, stored indefinitely, and used for various research purposes.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Screening laboratory values within 28 days prior to enrollment must meet the following criteria:
• Absolute neutrophil count \>=800/mcL
• Platelets \>=100,000/mcL
• Hemoglobin \>=10.0 g/dL
• Creatinine less than or equal to 1.31 mg/dL

You may not qualify if:

• A participant will be excluded if one or more of the following conditions apply:
• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.
• Prior use of antiretroviral therapy.
• Ongoing AIDS-related opportunistic infection (including oral thrush).
• Active drug or alcohol use or dependence in the opinion of the site investigator that would interfere with adherence to study requirements.
• Any history of a severe allergic reaction, including generalized urticaria, angioedema or anaphylaxis prior to enrollment, that has a reasonable risk of recurrence during the study.
• Physical finding on examination considered clinically significant.
• Hypertension that is not well controlled.
• Weight \>115 kg (253 pounds).
• Breast-feeding.
• Receipt of any investigational study product within 28 days prior to enrollment.
• Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (7)

University of Alabama HIV Clinic Clinical Research Site, AIDS Clinical Trials Group (ACTG)

Birmingham, Alabama, 35294, United States

Location

UCLA CARE Center, AIDS Clinical Trials Group (ACTG)

Los Angeles, California, 90035, United States

Location

Washington University Therapeutics, AIDS Clinical Trials Group (ACTG)

St Louis, Missouri, 63110, United States

Location

University of Cincinnati University Hospital, AIDS Clinical Trials Group (ACTG)

Cincinnati, Ohio, 45267, United States

Location

Ohio State University Clinical Research Site, AIDS Clinical Trials Group (ACTG)

Columbus, Ohio, 43210, United States

Location

Hospital of the University of Pennsylvania Clinical Research Site, AIDS Clinical Trials Group (ACTG)

Philadelphia, Pennsylvania, 19104-6056, United States

Location

Puerto Rico AIDS Clinical Trials Unit, AIDS Clinical Trials Group (ACTG)

San Juan, PR, 00935, Puerto Rico

Location

Related Publications (4)

• Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, Enama ME, DeZure A, Lynch RM, Gordon I, Plummer S, Hendel CS, Pegu A, Conan-Cibotti M, Sitar S, Bailer RT, Narpala S, McDermott A, Louder M, O'Dell S, Mohan S, Pandey JP, Schwartz RM, Hu Z, Koup RA, Capparelli E, Mascola JR, Graham BS; VRC 602 Study Team. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015 Dec;182(3):289-301. doi: 10.1111/cei.12692. Epub 2015 Sep 24.

  PMID: 26332605 BACKGROUND

• Lynch RM, Boritz E, Coates EE, DeZure A, Madden P, Costner P, Enama ME, Plummer S, Holman L, Hendel CS, Gordon I, Casazza J, Conan-Cibotti M, Migueles SA, Tressler R, Bailer RT, McDermott A, Narpala S, O'Dell S, Wolf G, Lifson JD, Freemire BA, Gorelick RJ, Pandey JP, Mohan S, Chomont N, Fromentin R, Chun TW, Fauci AS, Schwartz RM, Koup RA, Douek DC, Hu Z, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE; VRC 601 Study Team. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med. 2015 Dec 23;7(319):319ra206. doi: 10.1126/scitranslmed.aad5752.

  PMID: 26702094 BACKGROUND

• Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, Wang K, Bao S, Kraemer TD, Rath T, Zeng M, Schmidt SD, Todd JP, Penzak SR, Saunders KO, Nason MC, Haase AT, Rao SS, Blumberg RS, Mascola JR, Nabel GJ. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature. 2014 Oct 30;514(7524):642-5. doi: 10.1038/nature13612. Epub 2014 Aug 13.

  PMID: 25119033 BACKGROUND

• Happe M, Lynch RM, Fichtenbaum CJ, Heath SL, Koletar SL, Landovitz RJ, Presti RM, Santana-Bagur JL, Tressler RL, Holman LA, Novik L, Roa JC, Rothwell RS, Strom L, Wang J, Hu Z, Conan-Cibotti M, Bhatnagar AM, Dwyer B, Ko SH, Belinky F, Namboodiri AM, Pandey JP, Carroll R, Basappa M, Serebryannyy L, Narpala SR, Lin BC, McDermott AB, Boritz EA, Capparelli EV, Coates EE, Koup RA, Ledgerwood JE, Mascola JR, Chen GL, Tebas P; VRC 607/A5378 Study Team. Virologic effects of broadly neutralizing antibodies VRC01LS and VRC07-523LS on chronic HIV-1 infection. JCI Insight. 2025 Feb 24;10(4):e181496. doi: 10.1172/jci.insight.181496.

  PMID: 39989458 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: Martin Gaudinski, MD
• Organization: Vaccine Research Center, NIAID, NIH

martin.gaudinski@nih.gov

(301) 451-8715

Study Officials

• Martin R Gaudinski, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 21, 2016
• Study Start: April 24, 2017
• Primary Completion: January 15, 2020
• Study Completion: January 15, 2020
• Last Updated: January 30, 2025
• Results First Posted: February 23, 2021

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); PR (1)