Evaluating the Safety and Drug Levels of an Antibody Against HIV in Healthy, HIV-Uninfected Adults

NCT02165267 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 10411969
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 6

Brief Summary

Antibodies are natural proteins that the body makes to fight infections. Antibodies can also be manufactured like a drug and infused or injected into the body to prevent or treat a disease. The purpose of this study is to test the safety of and the body's response to an antibody against HIV in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (7)

• Assessment of local and systemic reactogenicity signs and symptoms

  Assessment occurs at each product administration and for 3 days after administration.

  Measured through Month 5.5 visit

• Measurements of laboratory measures of safety

  Measured through participants' last study visit at Month 8

• Assessment of adverse events

  Measured through participants' last study visit at Month 8

• Assessment of serious adverse events

  Measured through participants' last study visit at Month 8

• Number of early discontinuation of infusions

  The assessment will include the reason(s) for discontinuation of infusions and early study termination.

  Measured through participants' last study visit at Month 8

• Serum concentration of VRC01 in Groups 1-3 at Month 6

  Measured at Month 6

• Serum concentration of VRC01 28 and 56 days after each IV administration in Groups 4 and 5

  Measured 56 days after each IV administration

Secondary Outcomes (6)

• Magnitude of serum neutralization of a single VRC01 sensitive virus isolate as measured in the TZMbl assay at multiple timepoints

  Measured through participants' last study visit at Month 8

• Serum concentration of VRC01 in each group at multiple timepoints

  Measured through participants' last study visit at Month 8

• Serum concentration of anti-VRC01 antibodies in each group at multiple timepoints compared to corresponding VRC01 levels

  Measured through participants' last study visit at Month 8

• Mucosal levels of VRC01 in each group at multiple timepoints

  Measured through participants' last study visit at Month 8

• Magnitude of neutralization in genital, rectal, and oral secretions of a single VRC01 sensitive virus isolate as measured in the TZMbl assay at multiple timepoints

  Measured through participants' last study visit at Month 8

Study Arms (6)

Arm 1: VRC01 (6 IV infusions)

EXPERIMENTAL

Participants will receive an IV infusion of 40 mg/kg of VRC01 administered in 100 mL of normal saline over 1 hour at Day 0, followed by IV infusions of 20 mg/kg of VRC01 administered in 100 mL of normal saline over at least 30 minutes to 1 hour at Days 28, 56, 84, 112, and 140.

Biological: VRC01

Arm 2: VRC01 (3 IV infusions)

EXPERIMENTAL

Participants will receive an IV infusion of 40 mg/kg of VRC01 administered in 100 mL of normal saline over 1 hour at Day 0 and over at least 30 minutes to 1 hour at Days 56 and 112.

Biological: VRC01

Arm 3a: VRC01 (1 IV infusion plus multiple SC injections)

EXPERIMENTAL

Participants will receive an IV infusion of 40 mg/kg of VRC01 administered in 100 mL of normal saline over 1 hour at Week 0, followed by SC injection of 5 mg/kg of VRC01 administered every 2 weeks for 20 weeks.

Biological: VRC01

Arm 3b: Placebo for VRC01 (infusion plus injections)

PLACEBO COMPARATOR

Participants will receive an IV infusion of sodium chloride placebo administered in 100 mL of normal saline over 1 hour at Week 0, followed by SC injection of placebo for VRC01 administered every 2 weeks for 20 weeks.

Biological: SC placebo for VRC01; Biological: IV placebo for VRC01

Arm 4: 10 mg/kg of VRC01 (3 IV infusions)

EXPERIMENTAL

Participants will receive an IV infusion of 10 mg/kg of VRC01 administered in 100 mL of normal saline over 1 hour at Month 0 and over at least 30 minutes to 1 hour at Months 2 and 4.

Biological: VRC01

Arm 5: 30 mg/kg of VRC01 (3 IV infusions)

EXPERIMENTAL

Participants will receive an IV infusion of 30 mg/kg of VRC01 administered in 100 mL of normal saline over 1 hour at Month 0 and over at least 30 minutes to 1 hour at Months 2 and 4.

Biological: VRC01

Interventions

VRC01 BIOLOGICAL

Administered IV in 100 mL of normal saline (Sodium Chloride for Injection 0.9%, USP) or administered SC by needle and syringe injection.

Also known as: Human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB

Arm 1: VRC01 (6 IV infusions); Arm 2: VRC01 (3 IV infusions); Arm 3a: VRC01 (1 IV infusion plus multiple SC injections); Arm 4: 10 mg/kg of VRC01 (3 IV infusions); Arm 5: 30 mg/kg of VRC01 (3 IV infusions)

SC placebo for VRC01 BIOLOGICAL

Sterile, buffered aqueous solution of 25 mM Sodium Citrate, 50 mM Sodium Chloride, 150 mM L-Arginine Hydrochloride, 10% Dextran 40, and 0.005% Polysorbate 80 at pH 5.8 administered SC by needle and syringe injection

Also known as: SC placebo for VRC-PLAMAB068-00-AB

Arm 3b: Placebo for VRC01 (infusion plus injections)

IV placebo for VRC01 BIOLOGICAL

Sodium Chloride for Injection 0.9%, USP administered IV in 100 mL of normal saline (Sodium Chloride for Injection 0.9%, USP)

Also known as: Sodium Chloride for Injection 0.9%, USP

Arm 3b: Placebo for VRC01 (infusion plus injections)

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
• Weight at least 53 kg and up 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: participant demonstrates understanding of this study; completes a questionnaire prior to first infusion, 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, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Hemogram/Complete Blood Count (CBC)
• Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female, greater than or equal to 13.0 g/dL for participants who were born male
• White blood cell count equal to 2,500 to 12,000 cells/mm\^3
• Total lymphocyte count greater than or equal to 800 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 104 PSRT
• Investigational research agents received within 30 days before first infusion
• Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 104 study
• Pregnant or breastfeeding
• Vaccines and Other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 104 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 participants who have received an experimental vaccine(s) less than 6 months ago, eligibility for enrollment will be determined by the HVTN 104 PSRT on a case-by-case basis.
• Live attenuated vaccines other than influenza vaccine received within 10 days before first infusion and with no evidence of residual inflammation; 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 monoclonal antibodies (mAbs) whether licensed or investigational
• Immune System
• Immunosuppressive medications received within 30 days before first infusion. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy less than 11 days, with completion at least 30 days prior to enrollment.
• Serious adverse reactions to vaccines or to vaccine components, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child)
• Immunoglobulin received within 90 days before first infusion, unless eligibility for earlier enrollment is determined by the HVTN 104 PSRT.
• Autoimmune disease (Not excluded: participant with mild, stable, and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and adverse event \[AE\] assessments)

Sponsors & Collaborators

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

Study Sites (6)

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Mayer KH, Seaton KE, Huang Y, Grunenberg N, Isaacs A, Allen M, Ledgerwood JE, Frank I, Sobieszczyk ME, Baden LR, Rodriguez B, Van Tieu H, Tomaras GD, Deal A, Goodman D, Bailer RT, Ferrari G, Jensen R, Hural J, Graham BS, Mascola JR, Corey L, Montefiori DC; HVTN 104 Protocol Team; and the NIAID HIV Vaccine Trials Network. Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial. PLoS Med. 2017 Nov 14;14(11):e1002435. doi: 10.1371/journal.pmed.1002435. eCollection 2017 Nov.

  PMID: 29136037 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

VRC01 monoclonal antibody; Sodium Chloride; Injections

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Kenneth Mayer

  The Fenway Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 13, 2014
• First Posted: June 17, 2014
• Study Start: August 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (6)