Phase I, Open-Label, Dose-Escalation Study of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)
VRC 609
VRC 609: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20) to Healthy Adults
2 other identifiers
interventional
33
1 country
1
Brief Summary
Background: The experimental product in this study, N6LS, is a human monoclonal antibody. Antibodies are one way that the human body fights infection. Monoclonal means that all the antibodies in the product are the same. N6LS is directed against the HIV virus. There is no HIV in the N6LS study product and you cannot get HIV from this product. This study is the first time N6LS is tested in humans. It was given into a vein in the arm (intravenously, IV) or as an injection underneath the skin (subcutaneously, SC). The study also tested N6LS mixed with an enzyme, rHuPH20 (recombinant human hyaluronidase). rHuPH20 increases the spread of fluids injected underneath your skin (subcutaneously, SC) and allows for the rapid delivery of large volume injections that can be given with a single needle. It was given as a SC infusion using a small needle attached to an infusion pump. Study products were only given to healthy adults who are not infected with HIV. Objective: The main purpose of the study is to see if N6LS alone and N6LS mixed with rHuPH20 is safe in healthy adults. Another goal is to learn how amounts of N6LS in the body change over time. Study Plan: Assigned study groups depended on the dose of product, the numbers of times the product was given (once or three times at 12-week intervals), and how the product was given (IV or SC). Blood samples for research were collected at most of the visits. There were about 14 clinic visits over 6 months for all groups who got one dose of product, and about 26 clinic visits over 12 months for the groups who got three doses of product.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2018
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 24, 2018
CompletedFirst Posted
Study publicly available on registry
May 29, 2018
CompletedStudy Start
First participant enrolled
June 21, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 29, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
August 29, 2022
CompletedResults Posted
Study results publicly available
September 21, 2023
CompletedFebruary 1, 2024
December 1, 2023
4.2 years
May 24, 2018
August 28, 2023
January 3, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
Participants recorded the occurrence of solicited symptoms on a diary card for 3 days after each 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, Corrected Version 2.1.
3 days after each product administration, at approximately Day 3 for all dose groups, and at approximately Day 87 and Day 171 for repeat dose groups
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
Participants recorded the occurrence of solicited symptoms on a diary card for 3 days after each 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 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, Corrected Version 2.1.
3 days after each product administration, at approximately Day 3 for all dose groups, and at approximately Day 87 and Day 171 for repeat dose groups
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
Unsolicited adverse event (AE) data collection included AEs of all severities from the date of product administration through the Day 56 (8 weeks) after each product administration visit. After the Day 56 (8 weeks) after each product administration visit, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that require ongoing medical management (reported as a separate outcome) were recorded through the last study visit. The relationship between a non-serious 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 8 weeks after each product administration, at approximately Week 8 for all dose groups, and at Weeks 20 and 32 for repeat dose groups
Number of Participants With Serious Adverse Events (SAEs) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 24 for single dose groups and at Week 48 for repeat dose groups. 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 the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups
Number of Participants With New Chronic Medical Conditions Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 24 for single dose groups and at Week 48 for repeat dose groups. 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 the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
Abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV) platelets, and neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, alkaline phosphatase (ALP) and Comprehensive Metabolic Panel (CMP)). Complete Blood Count (CBC) with differential and chemistry (ALT, AST, ALP, creatinine and CMP) results were collected at different timepoints throughout the study per the protocol's schedule of evaluations. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.
Day 0 through 8 weeks after each product administration, at approximately Week 8 for all dose groups, and at Weeks 20 and 32 for repeat dose groups
Secondary Outcomes (6)
Number of Participants Who Produced N6LS Anti-drug Antibodies (ADA) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20
Baseline and Weeks 4 and 8 for single dose groups, or Baseline and Weeks 4, 28, and 32 for repeat dose groups
Pharmacokinetic (PK) Parameters of N6LS: Maximum Observed Serum Concentration (Cmax)
Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups
Pharmacokinetic (PK) Parameters of N6LS: Time to Reach Maximum Observed Serum Concentration (Tmax)
Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups
Pharmacokinetic (PK) Parameters of N6LS: Beta Half-life (T1/2b)
Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups
Pharmacokinetic (PK) Parameters of N6LS: Clearance Rate
Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups
- +1 more secondary outcomes
Study Arms (8)
Group 1: N6LS (5 mg/kg IV) single dose
EXPERIMENTALN6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0)
Group 2: N6LS (5 mg/kg SC) single dose
EXPERIMENTALN6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0)
Group 3: N6LS (20 mg/kg IV) single dose
EXPERIMENTALN6LS (20 mg/kg) administered by IV infusion (Day 0)
Group 4: N6LS (40 mg/kg IV) single dose
EXPERIMENTALN6LS (40 mg/kg) administered by IV infusion (Day 0)
Group 5: N6LS (5 mg/kg SC) repeat dose
EXPERIMENTALN6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24)
Group 6: N6LS (20 mg/kg IV) repeat dose
EXPERIMENTALN6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24)
Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) single dose
EXPERIMENTALN6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0)
Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) single dose
EXPERIMENTALN6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0)
Interventions
N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.
Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Eligibility Criteria
You may qualify if:
- A volunteer must have met all of the following criteria:
- Willing and able to complete the informed consent process.
- to 50 years of age.
You may not qualify if:
- Willing to have blood samples collected, stored indefinitely, and used for research purposes.
- Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
- Screening laboratory criteria within 84 days prior to enrollment meeting the following criteria:
- White blood cell count (WBC): 2,500-12,000/mm\^3.
- WBC differential: Within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
- Platelets: 125,000-400,000/mm\^3.
- Hemoglobin: Within institutional normal range or accompanied by PI or designee approval.
- Creatinine: less than or equal to 1.1 x Upper Limit of Normal (ULN).
- Alanine aminotransferase (ALT): less than or equal to 1.25 x ULN.
- Aspartate aminotransferase (AST): less than or equal to 1.25 x ULN.
- Negative for HIV infection by an FDA approved method of detection.
- Female-Specific Criteria:
- If a woman is of reproductive potential and sexually active with a male partner, then she agrees to use an effective means of birth control from the time of study enrollment until the last study visit, or to be monogamous with a partner who has had a vasectomy.
- Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.
- A volunteer would have been excluded if one or more of the following conditions applied:
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (4)
Huang J, Kang BH, Ishida E, Zhou T, Griesman T, Sheng Z, Wu F, Doria-Rose NA, Zhang B, McKee K, O'Dell S, Chuang GY, Druz A, Georgiev IS, Schramm CA, Zheng A, Joyce MG, Asokan M, Ransier A, Darko S, Migueles SA, Bailer RT, Louder MK, Alam SM, Parks R, Kelsoe G, Von Holle T, Haynes BF, Douek DC, Hirsch V, Seaman MS, Shapiro L, Mascola JR, Kwong PD, Connors M. Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth. Immunity. 2016 Nov 15;45(5):1108-1121. doi: 10.1016/j.immuni.2016.10.027.
PMID: 27851912BACKGROUNDGaudinski 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: 29364886BACKGROUNDLedgerwood 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: 26332605BACKGROUNDWu RL, Houser KV, Gaudinski MR, Widge AT, Awan SF, Carter CA, Holman LA, Saunders J, Hendel CS, Eshun A, Whalen WR, Wang X, Arthur A, Cunningham JE, Beck A, Casazza JP, Yamshchikov GV, Rothwell RS, Strom L, Dittakavi T, Happe M, Hickman SP, Conan-Cibotti M, Carlton K, Zhang L, Huang Y, Capparelli EV, Castro M, Lin BC, O'Connell S, Flach BS, Bailer RT, Narpala SR, Serebryannyy L, McDermott AB, Arnold FJ, Gall JG, Vazquez S, Berkowitz NM, Gordon IJ, Chen GL, Kwong PD, Huang J, Pierson TC, Connors M, Mascola JR, Zhou T, Doria-Rose NA, Koup RA, Dropulic LK; VRC 609 study team. Safety and pharmacokinetics of N6LS, a broadly neutralising monoclonal antibody for HIV: a phase 1, open-label, dose-escalation study in healthy adults. Lancet HIV. 2025 Jul;12(7):e485-e495. doi: 10.1016/S2352-3018(25)00041-4. Epub 2025 May 20.
PMID: 40409326DERIVED
Related Links
Results Point of Contact
- Title
- VRC Clinical Trials Program Leadership
- Organization
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
Richard L Wu, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Publication Agreements
- PI is Sponsor Employee
- Yes
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
May 24, 2018
First Posted
May 29, 2018
Study Start
June 21, 2018
Primary Completion
August 29, 2022
Study Completion
August 29, 2022
Last Updated
February 1, 2024
Results First Posted
September 21, 2023
Record last verified: 2023-12
Data Sharing
- IPD Sharing
- Will not share
Individual participant data (IPD) is not shared because it has limited value in a small phase 1 trial of healthy volunteers. We instead report non-IPD data as required in ClinicalTrials.gov.