Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously to Healthy Adults

VRC 609: APhase 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 to Healthy Adults

Study Design:

This is the first study in healthy adults of the N6LS monoclonal antibody (MAb). It is a
dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics (PK) of
N6LS. The hypothesis is that N6LS administration to healthy adults will be safe by the
intravenous (IV) and subcutaneous (SC) routes. A secondary hypothesis is that N6LS will be
detectable in human sera with a definable half-life.

Product Description:

N6LS (VRC-HIVMAB091-00-AB ) is a human MAb targeted to the HIV-1 CD4 binding site. It was
developed by the VRC/NIAID/NIH and manufactured under current Good Manufacturing Practice
(cGMP) regulations at the VRC Vaccine Pilot Plant operated under contract by the Vaccine
Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick, MD. The
product is provided as a sterile aqueous buffered solution in 10 mL glass vials at a
concentration of 100 +/- 10 mg/mL and volume of 6.25 +/- 0.10 mL.

Subjects: Healthy adults, 18-50 years of age.

Study Plan:

This open-label study will include 6 dose groups to assess N6LS given as a single IV infusion
at the 5, 20, or 40 mg/kg dose level (Groups 1, 3,4); a single SC injection at the 5 mg/kg
dose level (Group 2); or in 3 administrations, 12 weeks apart by SC injection at the 5 mg/kg
dose level (Group 5), or by IV infusion at the 20 mg/kg dose level (Group 6). Enrollments
will initially open with Groups 1, 2 and 5; followed by the sequential activation of Groups
3, 4, and 6.

Study Duration:

Subject study participation will be approximately 24 weeks for subjects in Groups 1 to 4 and
48 weeks for subjects in Groups 5 and 6.

- INCLUSION CRITERIA:

A subject must meet all of the following criteria:

1. Willing and able to complete the informed consent process.

2. 18 to 50 years of age.

3. Based on history and examination, must be in good general health and without history
of any of the conditions listed in the exclusion criteria.

4. Willing to have blood samples collected, stored indefinitely, and used for research
purposes.

5. Able to provide proof of identity to the satisfaction of the study clinician
completing the enrollment process.

6. Screening laboratory criteria within 84 days prior to enrollment must meet 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).

- ALT: less than or equal to 1.25 x ULN.

- AST: less than or equal to 1.25 x ULN.

- Negative for HIV infection by an FDA approved method of detection.

Female-Specific Criteria:

7. 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.

8. 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 subject will be excluded if one or more of the following conditions apply:

1. Prior receipt of licensed or investigational monoclonal antibody.

2. Weight > 115 kg.

3. Any history of a severe allergic reaction with generalized urticaria, angioedema or
anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of
recurrence during the study.

4. Hypertension that is not well controlled.

5. Woman who is breast-feeding, or planning to become pregnant during the study
participation.

6. Receipt of any investigational study agent within 28 days prior to enrollment.

7. Any other chronic or clinically significant medical condition that in the opinion of
investigator would jeopardize the safety or rights of the subject 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.