Clinical trial NCT03015181: VRC 605: Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults
Official title: VRC 605: A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Prevention
Keywords: Broadly Neutralizing
HIV Prevention
Anti-Drug Antibody
HIV-1
Immune Response
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2017-01-09
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: Background:

Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat HIV-1 infected people.

Objective:

To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy adults.

Eligibility:

Healthy people ages 18-50

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Participants will be assigned to 1 of 7 groups:

Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks.

Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48 weeks.

Participants will get the drug in 1 of 2 ways:

Infusion into a vein over at least 30 minutes. Participants will have blood tests 1, 3, and 6 hours after the infusion. They will have 1-3 visits during that week. Those in Group 7 will have 4-5 visits in the week after their second and third doses.

Injection into the fatty tissue under the skin. Participants will have blood tests before the injection. They will have 1-3 visits during that week. Those in Group 6 will have 4-5 visits after the second and third doses.

Visits include:

Physical exam

Blood and urine tests

Optional oral swabs to collect saliva

Participants will keep a diary of their temperature and symptoms for 3 days after each dose.

Detailed description: This is the first study of the VRC-HIVMAB075-00-AB (VRC07-523LS) monoclonal antibody (MAb) in healthy adults. It is a phase 1, dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics of VRC07-523LS. The hypothesis is that VRC07-523LS will be safe for administration to healthy adults by the intravenous (IV) and subcutaneous (SC) routes.

Healthy adults 18-50 years of age will be enrolled. There are 4 open-label, dose escalations of VRC07-523LS from 1 mg/kg IV to 40 mg/kg IV, 1 route escalation from IV to SC, and 2 open-label groups to assess repeat dosing. Groups 1-5 are expected to include 3 subjects and Groups 6-7 are expected to enroll 5 subjects. Subjects will be followed for 24 weeks after the last study product administration.

Eligibility criteria: * INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

* Able and willing to complete the informed consent process.
* 18 to 50 years of age.
* Based on history and examination, must be in good general health and without history of any of the conditions listed in the exclusion criteria.
* 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.
* Willing to adhere to reduced risk sexual behavior during study participation.
* Screening laboratory values within 84 days prior to enrollment must meet the following criteria:

  * White Blood Cell (WBC) 2,500-12,000/mm\^3.
  * WBC differential either 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.
  * 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.
* Negative for HIV infection by the 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.

EXCLUSION CRITERIA:

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

* Previous receipt of licensed or investigational monoclonal antibody.
* Weight \>115 kg.
* 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.
* Hypertension that is not well controlled.
* Woman who is breast-feeding, or planning to become pregnant during the study participation.
* Receipt of any investigational study agent 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, including but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.

Primary outcomes:
measure: Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration
timeFrame: 3 days after each product administration
measure: Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration
timeFrame: 7 days after each product administration
measure: Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events
timeFrame: Through 24 weeks after the last product administration
measure: Number of Subjects Reporting Serious Adverse Events
timeFrame: Through 24 weeks after the last product administration
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups
timeFrame: Up to 24 weeks post product administration
measure: Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Multiple Dose Groups
timeFrame: Through 24 weeks after the last product administration
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS
timeFrame: Through 24 weeks after the last product administration for Groups 1-5 and through 8 weeks after the last product administration for Groups 6 and 7
measure: 4 Week Mean Serum Concentration of VRC07-523LS
timeFrame: Week 4 post product administration
measure: 12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups
timeFrame: Week 12 post product administration
measure: 12 Week Mean Serum Concentration of VRC07-523LS: Multiple Dose Groups
timeFrame: Up to 12 weeks after each product administration
measure: Area Under the Curve (AUC(0-inf)): Single Dose Groups
timeFrame: Administration (0h) to 24 weeks post product administration
measure: Area Under the Curve (AUC0-84D): Multiple Dose Groups
timeFrame: Administration (0h) up to 84 days after each product administration
measure: VRC07-523LS Clearance Rate
timeFrame: Administration (0h) to 28 days post product administration
measure: Overall IV Half-life (T1/2) of VRC07-523LS
timeFrame: Administration (0h) to 56 days post product administration
measure: Number of Single Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
timeFrame: Weeks 4 and 8 post product administration
measure: Number of Multiple Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
timeFrame: Weeks 4, 28 and 32 after the first product administration
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Martin R Gaudinski, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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