vrc 605: safety and pharmacokinetics of a human monoclonal antibody, vrc-hivmab075-00-ab (vrc07-523ls), administered intravenously or subcutaneously to healthy adults

Conditions: HIV Prevention

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.

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.

Keywords: broadly neutralizing hiv prevention anti-drug antibody hiv-1 immune response