Evaluating the Safety, Pharmacokinetics, and Anti-Viral Activity of VRC01 and VRC01LS in the Serum and Mucosa of Healthy, HIV-Uninfected Adults

NCT02797171 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 11620733
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 4

Brief Summary

This study will evaluate the safety, pharmacokinetics, and antiviral activity of VRC-HIVMAB060-00-AB (VRC01) and VRC-HIVMAB080-00-AB (VRC01LS) in the serum and mucosa of healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (15)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 days after each infusion at months 0, 2, 3, 4 or 6 (infusion visits depending on which group participants are in)

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[March 2017\] The maximum grade observed for each symptom over the time frame is presented.

  Measured through 3 days after each infusion at months 0, 2, 3, 4 or 6 (infusion visits depending on which group participants are in)

• Chemistry and Hematology Laboratory Measures

  alkaline phosphate (ALP) (U/L), aspartate aminotransferase (AST) (U/L), alanine aminotransferase (ALT) (U/L) (Doesn't mention about lab grade \> 1 )

  Measured through IV infusion at visits 1 (screening), 4 (day 1-15), 7 (day 57-71), 10 (day 99-113), 12 (day 127-141), 14 (day 169-183), 16 (day 252-267), and 18 (day 442-456) (visits depending on which group participants are in)

• Chemistry and Hematology Laboratory Measures - Creatinine, Hemoglobin

  Chemistry and Hematology Laboratory Measures - creatinine (g/dl), hemoglobin (g/dl)

  Measured through IV infusion at visits 1 (screening), 4 (day 1-15), 7 (day 57-71), 10 (day 99-113), 12 (day 127-141), 14 (day 169-183), 16 (day 252-267), and 18 (day 442-456) (visits depending on which group participants are in)

• Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC)

  Chemistry and Hematology Laboratory Measures - lymphocyte count (1000/mm3), neutrophil count (1000/mm3), platelets (1000/mm3), white blood cells (WBC) (1000/mm3)

  Measured through IV infusion at visits 1 (screening), 4 (day 1-15), 7 (day 57-71), 10 (day 99-113), 12 (day 127-141), 14 (day 169-183), 16 (day 252-267), and 18 (day 442-456) (visits depending on which group participants are in)

• Number of Participants With Chemistry and Hematology Laboratory Measures - Counts of Lab Grade > 1

  Number of Participants with Chemistry and Hematology Laboratory Measures - Counts of Lab Grade \> 1 for alkaline phosphate (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC).

  Measured through IV infusion at visits 1 (screening), 4 (day 1-15), 7 (day 57-71), 10 (day 99-113), 12 (day 127-141), 14 (day 169-183), 16 (day 252-267), and 18 (day 442-456) (visits depending on which group participants are in)

• Number of Participants Reporting Adverse Events (AEs)

  For participants reporting multiple AEs over the time frame, the maximum severity is counted

  Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in)

• Number of Participants Reporting Serious Adverse Events (SAEs)

  For participants reporting multiple AEs over the time frame, the maximum severity is counted

  Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in)

• Rates of Participant Discontinuation

  Tabulated by reason for discontinuation and treatment arm

  Measured through participant's last study visit, at 6 months to 1 1/2 years after study entry (depending on which group participants are in)

• Unnormalized Serum Concentration of VRC01 Out to Month 6 After the Last Infusion (for Groups 1, 2, and 4)

  Outcome measure will not be ready before the anticipated reporting date. VRC01/LS levels were measured by Singulex assay. VRC01/LS levels of study samples are calibrated via the respective standard curve on each assay plate. A five-parameter logistic (5PL) model is used to fit the standard curve data using the nCal package in R. Outcome measure is the estimated concentration of VRC01/VRC01LS.

  Measured through 6 months after the last infusion

• IgG-normalized Serum Concentration of VRC01 Out to Month 6 After the Last Infusion (for Groups 1, 2, and 4)

  Outcome measure will not be ready before the anticipated reporting date. VRC01/LS levels were measured by Singulex assay. VRC01/LS levels and total IgG levels of study samples are calibrated via the respective standard curve on each assay plate. A five-parameter logistic (5PL) model is used to fit the standard curve data using the nCal package in R. Outcome measure is the IgG-normalized VRC01/VRC01LS levels performed by dividing VRC01/LS levels (pg/mL) by the total IgG concentrations (ng/mL)

  Measured through 6 months after the last infusion

• Protein-normalized Serum Concentration of VRC01 Out to Month 6 After the Last Infusion (for Groups 1, 2, and 4)

  Outcome measure will not be ready before the anticipated reporting date. VRC01/LS levels were measured by Singulex assay. VRC01/LS levels and total protein levels of study samples are calibrated via the respective standard curve on each assay plate. A five-parameter logistic (5PL) model is used to fit the standard curve data using the nCal package in R. Outcome measure is the protein-normalized VRC01/VRC01LS levels performed by dividing VRC01/LS levels (pg/mL) by the total protein concentrations (ng/mL)

  Measured through 6 months after the last infusion

• Unnormalized Levels of VRC01 in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues (for Groups 1, 2, and 4)

  Outcome measure will not be ready before the anticipated reporting date. VRC01/LS levels were measured by Singulex assay. VRC01/LS levels of study samples are calibrated via the respective standard curve on each assay plate. A five-parameter logistic (5PL) model is used to fit the standard curve data using the nCal package in R. Outcome measure is the estimated concentration of VRC01/VRC01LS.

  Measured through 6 months after the last infusion

• IgG-normalized Levels of VRC01 in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues (for Groups 1, 2, and 4)

  Outcome measure will not be ready before the anticipated reporting date. VRC01/LS levels were measured by Singulex assay. VRC01/LS levels and total IgG levels of study samples are calibrated via the respective standard curve on each assay plate. A five-parameter logistic (5PL) model is used to fit the standard curve data using the nCal package in R. Outcome measure is the IgG-normalized VRC01/VRC01LS levels performed by dividing VRC01/LS levels (pg/mL) by the total IgG concentrations (ng/mL)

  Measured through 6 months after the last infusion

• Protein-normalized Levels of VRC01 in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues (for Groups 1, 2, and 4)

  Outcome measure will not be ready before the anticipated reporting date. VRC01/LS levels were measured by Singulex assay. VRC01/LS levels and total protein levels of study samples are calibrated via the respective standard curve on each assay plate. A five-parameter logistic (5PL) model is used to fit the standard curve data using the nCal package in R. Outcome measure is the protein-normalized VRC01/VRC01LS levels performed by dividing VRC01/LS levels (pg/mL) by the total protein concentrations (ng/mL)

  Measured through 6 months after the last infusion

Secondary Outcomes (1)

• Ex Vivo Inhibition of HIV-1 Infectivity in Tissue Biopsies (for Groups 1, 2, and 3)

  Cervical biopsies collected at visits 2 and 14; Rectal biopsies collected at visits 2, 14, 15, 16, 17, 18, 19 (19 not apply for Du422.1); Vaginal biopsies collected at visits 2 and 14, 15, 16, 17. RLU measured every 3 days, during culture days 3-21.

Study Arms (5)

Group 1

EXPERIMENTAL

Participants will receive 10 mg/kg of VRC01 at Months 0, 2, 4, and 6.

Biological: VRC01

Group 2

EXPERIMENTAL

Participants will receive 30 mg/kg of VRC01 at Months 0, 2, 4, and 6.

Biological: VRC01

Group 3

EXPERIMENTAL

Participants will receive 30 mg/kg of VRC01LS at Months 0, 3, and 6.

Biological: VRC01LS

Group 4

EXPERIMENTAL

Participants will receive 30 mg/kg of VRC01 at Month 0.

Biological: VRC01

Group 5

EXPERIMENTAL

Participants will receive 30 mg/kg of VRC01LS at Month 0.

Biological: VRC01LS

Interventions

VRC01 BIOLOGICAL

Administered by intravenous (IV) infusion

Also known as: VRC-HIVMAB060-00-AB

Group 1; Group 2; Group 4

VRC01LS BIOLOGICAL

Administered by intravenous (IV) infusion

Also known as: VRC-HIVMAB080-00-AB

Group 3; Group 5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria:
• Age of 18 to 50 years
• Weight less than or equal to 115 kg
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to enrollment with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent until completion of the last study visit
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria:
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Assessed by the clinic staff as being at "low risk" for HIV infection \[low risk guidelines are found on the protocol home page on the HVTN Members' site (https://members.hvtn.org/protocols/hvtn116)\] and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Hemogram/CBC
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
• White blood cell count equal to 2,500 to 12,000 cells/mm\^3

You may not qualify if:

• General
• Blood products received within 120 days before first infusion, unless eligibility for earlier enrollment is determined by the HVTN 116 PSRT
• Investigational research agents received within 30 days before first infusion
• Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the HVTN 116 study
• Pregnant or breastfeeding
• Active duty U.S. military personnel with the potential of being deployed during the study
• Vaccines and Other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 116 PSRT will determine eligibility on a case-by-case basis.
• Non-HIV experimental vaccine(s) received within the last 6 months in a prior vaccine trial. Exceptions may be made for some vaccines and vaccine trials. For volunteers who have received an experimental vaccine(s) less than 6 months ago, eligibility for enrollment will be determined by the HVTN 116 PSRT on a case-by-case basis.
• Live attenuated vaccines other than influenza vaccine received within 10 days before first infusion or scheduled within 10 days after first infusion (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Previous receipt of humanized or human mAbs whether licensed or investigational
• Immune System
• Serious adverse reactions to VRC01 and VRC01LS formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
• Immunodeficiency
• Clinically Significant Medical Conditions

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Groote Schuur HIV CRS

Cape Town, Western Cape, 7925, South Africa

Location

Related Publications (1)

• Lemos MP, Astronomo RD, Huang Y, Narpala S, Prabhakaran M, Mann P, Paez CA, Lu Y, Mize GJ, Glantz H, Westerberg K, Colegrove H, Smythe KS, Lin M, Pierce RH, Hutter J, Frank I, Mascola JR, McDermott AB, Bekker LG, McElrath MJ. Enhanced and sustained biodistribution of HIV-1 neutralizing antibody VRC01LS in human genital and rectal mucosa. Nat Commun. 2024 Nov 28;15(1):10332. doi: 10.1038/s41467-024-54580-9.

  PMID: 39609400 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

VRC01 monoclonal antibody

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

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Julie McElrath

  Seattle Vaccine Trials Unit

  STUDY CHAIR

• Linda-Gail Bekker

  Desmond Tutu HIV Centre

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 13, 2016
• Study Start: March 1, 2017
• Primary Completion: June 5, 2019
• Study Completion: June 5, 2019
• Last Updated: March 20, 2024
• Results First Posted: January 8, 2021

Record last verified: 2022-08

Locations

ZA (1); US (3)