Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), With Broad HIV-1 Neutralizing Activity, Administered Intravenously or Subcutaneously to Healthy Adults

VRC 606: A Phase 1, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human
Monoclonal Antibody, VRC-HIVMAB080-00-AB (VRC01LS), and VRC-HIVMAB060-00-AB (VRC01),
Administered Intravenously or Subcutaneously to Healthy Adults.

Study Design: This is the first study of the VRC-HIVMAB080-00-AB (VRC01LS) monoclonal
antibody (MAb) in healthy adults. It is a dose-escalation study to examine safety,
tolerability, dose, and pharmacokinetics of VRC01LS. The hypothesis is that VRC01LS will be
safe to administer to healthy adults by the intravenous (IV) and subcutaneous (SC) routes.
The secondary hypothesis is that VRC01LS will be detectable in human sera with a definable
half-life. With protocol amendment, Group 7 and Group 8 were added to the protocol Version
2.0 to evaluate VRC01 and VRC01LS safety and pharmacokinetics in the same study.

Product Description: VRC-HIVMAB080-00-AB (VRC01LS) and VRC-HIVMAB060-00-AB (VRC01) are human
MAb targeted to the CD4 binding site of HIV-1. VRC01LS is a modification of the VRC01 MAb
(which has been shown to be safe in human studies) with the addition of the LS , 2-amino acid
mutation designed to improve the half-life of the antibody. VRC01LS and VRC01 were developed
by VRC/NIAID/NIH and manufactured under cGMP at the VRC Pilot Plan operated under contract by
the Vaccine Clinical Material Program operated for NIAID/VRC by Leidos Biomedical Research,
Inc., Frederick, MD. Vials are provided at 100 mg/mL.

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

Study Plan: There are 4 open-label, dose escalation groups (Groups 1-4) to assess VRC01LS
administered IV and SC once per subject. 2 open-label groups (Groups 5 and 6) to assess
VRC01LS at 5 mg/kg SC or at 20 mg/kg IV administered every 12 weeks for a total of 3
administrations per subject, and 2 open-label groups (Groups 7 and 8) to assess VRC01 at 5
mg/kg SC or at 20 mg/kg IV administered every 4 weeks for a total of 2 administrations per
subject. Subjects will be randomized into Group 1 or Group 2 at a 1:1 ratio, or directly
enrolled into Groups 3-6 per the dose escalation and safety evaluation plan. Enrollments into
Group 7 and Group 8 will be randomized at a 1:1 ratio.

Study Duration: Subjects will be followed for 24 weeks after the last study product
administration.

- INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

1. Able and willing to complete the informed consent process.

2. 18 to 50 years of age.

3. Based on history and examination, must be in general good health 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 values within 84 days prior to enrollment must meet the following
criteria:

- 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 to 400,000/mm(3).

- Hemoglobin within institutional normal range.

- Creatinine less than or equal to 1.1 x ULN.

- ALT less than or equal to 1.25 x ULN.

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

Female-Specific Criteria:

7. If a woman is secually active with a male partner and has no history of hysterectomy,
tubal ligation, or menopause, then she agrees to use either a prescription birth
control method or barrier birth control method from the time of study enrollment until
the last study visit, or to have a monogamous 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 volunteer will be excluded if one or more of the following conditions apply:

1. Previous receipt of monoclonal antibody whether licensed or investigational.

2. Weight >115 kg.

3. 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.

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 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.