Trial Outcomes & Findings for Phase I, Open-Label, Dose-Escalation Study of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20) (NCT NCT03538626)

Last Updated: 2024-02-01

Results Overview

Participants recorded the occurrence of solicited symptoms on a diary card for 3 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

33 participants

Primary outcome timeframe

3 days after each product administration, at approximately Day 3 for all dose groups, and at approximately Day 87 and Day 171 for repeat dose groups

Results posted on

2024-02-01

Participant Flow

Healthy adults were recruited for the study at the NIH Clinical Center in Bethesda, Maryland, USA.

Participant milestones

Participant milestones
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Overall Study STARTED	3	4	3	3	5	5	5	5
Overall Study Received First Product Administration	3	3	3	3	5	5	5	5
Overall Study Received All Product Administrations	3	3	3	3	5	5	5	5
Overall Study COMPLETED	3	3	3	3	5	5	4	5
Overall Study NOT COMPLETED	0	1	0	0	0	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Overall Study Withdrawal by Subject	0	1	0	0	0	0	0	0
Overall Study Lost to Follow-up	0	0	0	0	0	0	1	0

Baseline Characteristics

Phase I, Open-Label, Dose-Escalation Study of a Human Monoclonal Antibody, VRC-HIVMAB091-00-AB (N6LS), Administered Intravenously or Subcutaneously With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=4 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Total n=33 Participants Total of all reporting groups
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants
Weight (kg)	79.9 kg STANDARD_DEVIATION 16.0 • n=5 Participants	88.5 kg STANDARD_DEVIATION 17.1 • n=7 Participants	90.7 kg STANDARD_DEVIATION 3.2 • n=5 Participants	61.7 kg STANDARD_DEVIATION 11.8 • n=4 Participants	82.0 kg STANDARD_DEVIATION 15.3 • n=21 Participants	74.7 kg STANDARD_DEVIATION 13.8 • n=8 Participants	83.9 kg STANDARD_DEVIATION 5.6 • n=8 Participants	73.4 kg STANDARD_DEVIATION 9.3 • n=24 Participants	79.4 kg STANDARD_DEVIATION 13.6 • n=42 Participants
Age, Continuous	30.3 years STANDARD_DEVIATION 7.4 • n=5 Participants	31.3 years STANDARD_DEVIATION 7.4 • n=7 Participants	29.0 years STANDARD_DEVIATION 6.6 • n=5 Participants	28.0 years STANDARD_DEVIATION 7.8 • n=4 Participants	31.0 years STANDARD_DEVIATION 8.5 • n=21 Participants	26.2 years STANDARD_DEVIATION 7.8 • n=8 Participants	37.6 years STANDARD_DEVIATION 12.5 • n=8 Participants	32.8 years STANDARD_DEVIATION 12.0 • n=24 Participants	31.1 years STANDARD_DEVIATION 9.0 • n=42 Participants
Age, Customized 21-30 years	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	4 Participants n=8 Participants	2 Participants n=8 Participants	3 Participants n=24 Participants	18 Participants n=42 Participants
Age, Customized 31-40 years	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	10 Participants n=42 Participants
Age, Customized 41-50 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants	2 Participants n=24 Participants	5 Participants n=42 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants	3 Participants n=8 Participants	2 Participants n=8 Participants	3 Participants n=24 Participants	19 Participants n=42 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants	3 Participants n=8 Participants	2 Participants n=24 Participants	14 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	3 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants	5 Participants n=8 Participants	4 Participants n=8 Participants	5 Participants n=24 Participants	30 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	6 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	4 Participants n=42 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=8 Participants	3 Participants n=8 Participants	4 Participants n=24 Participants	20 Participants n=42 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	2 Participants n=42 Participants

PRIMARY outcome

Timeframe: 3 days after each product administration, at approximately Day 3 for all dose groups, and at approximately Day 87 and Day 171 for repeat dose groups

Population: Population included all enrolled participants who received at least one dose of study product and provided safety data (via diary card). One participant in Group 2 withdrew from the study prior to receiving study product.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pain/Tenderness · None	3 Participants	1 Participants	3 Participants	3 Participants	1 Participants	5 Participants	3 Participants	1 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pain/Tenderness · Mild	0 Participants	2 Participants	0 Participants	0 Participants	4 Participants	0 Participants	2 Participants	3 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pain/Tenderness · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pain/Tenderness · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Bruising · None	3 Participants	3 Participants	3 Participants	3 Participants	5 Participants	4 Participants	5 Participants	5 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Bruising · Mild	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Bruising · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Bruising · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Swelling · None	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	5 Participants	4 Participants	4 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Swelling · Mild	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Swelling · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Swelling · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Redness · None	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	5 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Redness · Mild	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Redness · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	3 Participants	1 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Redness · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	4 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pruritis (Itching) · None	3 Participants	3 Participants	3 Participants	3 Participants	3 Participants	5 Participants	4 Participants	2 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pruritis (Itching) · Mild	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	2 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pruritis (Itching) · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Pruritis (Itching) · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Local Symptom · None	3 Participants	1 Participants	3 Participants	3 Participants	1 Participants	4 Participants	0 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Local Symptom · Mild	0 Participants	2 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Local Symptom · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	3 Participants	1 Participants
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Local Symptom · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	4 Participants

PRIMARY outcome

Timeframe: 3 days after each product administration, at approximately Day 3 for all dose groups, and at approximately Day 87 and Day 171 for repeat dose groups

Participants recorded the occurrence of solicited symptoms on a diary card for 3 days after each study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Nausea · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Malaise · None	3 Participants	3 Participants	2 Participants	3 Participants	4 Participants	5 Participants	5 Participants	4 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Malaise · Mild	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Malaise · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Malaise · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Myalgia · None	3 Participants	3 Participants	3 Participants	3 Participants	4 Participants	5 Participants	5 Participants	5 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Myalgia · Mild	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Myalgia · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Myalgia · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Headache · None	2 Participants	3 Participants	1 Participants	2 Participants	4 Participants	5 Participants	5 Participants	5 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Headache · Mild	1 Participants	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Headache · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Headache · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Chills · None	3 Participants	3 Participants	3 Participants	2 Participants	5 Participants	5 Participants	5 Participants	5 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Chills · Mild	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Chills · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Chills · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Nausea · None	3 Participants	3 Participants	3 Participants	2 Participants	4 Participants	5 Participants	5 Participants	4 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Nausea · Mild	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Nausea · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Temperature (Fever) · None	3 Participants	3 Participants	3 Participants	3 Participants	5 Participants	5 Participants	5 Participants	5 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Temperature (Fever) · Mild	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Temperature (Fever) · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Temperature (Fever) · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Joint Pain · None	3 Participants	3 Participants	3 Participants	3 Participants	5 Participants	5 Participants	5 Participants	5 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Joint Pain · Mild	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Joint Pain · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Joint Pain · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Systemic Symptom · None	2 Participants	3 Participants	1 Participants	2 Participants	2 Participants	5 Participants	5 Participants	3 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Systemic Symptom · Mild	1 Participants	0 Participants	2 Participants	1 Participants	3 Participants	0 Participants	0 Participants	2 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Systemic Symptom · Moderate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Any Systemic Symptom · Severe	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 0 through 8 weeks after each product administration, at approximately Week 8 for all dose groups, and at Weeks 20 and 32 for repeat dose groups

Population: Population included all enrolled participants who received at least one dose of study product and had safety data collected (via clinical assessment and/or lab results). One participant in Group 2 withdrew from the study prior to receiving study product.

Unsolicited adverse event (AE) data collection included AEs of all severities from the date of product administration through the Day 56 (8 weeks) after each product administration visit. After the Day 56 (8 weeks) after each product administration visit, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions that require ongoing medical management (reported as a separate outcome) were recorded through the last study visit. The relationship between a non-serious AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Related to Study Product	0 Participants	2 Participants	1 Participants	0 Participants	1 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Unrelated to Study Product	1 Participants	1 Participants	1 Participants	2 Participants	2 Participants	3 Participants	2 Participants	2 Participants
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Total Number of Participants who had One or More Non-Serious Unsolicited AE	1 Participants	3 Participants	2 Participants	2 Participants	3 Participants	5 Participants	2 Participants	3 Participants

PRIMARY outcome

Timeframe: Day 0 after product administration through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

SAEs were recorded from receipt of first study product administration through the last expected study visit at Week 24 for single dose groups and at Week 48 for repeat dose groups. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants With Serious Adverse Events (SAEs) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 0 after product administration through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

New chronic medical conditions that required ongoing medical management were recorded from receipt of first study product administration through the last expected study visit at Week 24 for single dose groups and at Week 48 for repeat dose groups. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants With New Chronic Medical Conditions Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 0 through 8 weeks after each product administration, at approximately Week 8 for all dose groups, and at Weeks 20 and 32 for repeat dose groups

Population: Population included all enrolled participants who received at least one dose of study product and had safety data collected via laboratory results. One participant in Group 2 withdrew from the study prior to receiving study product.

Abnormal laboratory results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included hematology (hemoglobin, hematocrit, mean corpuscular volume (MCV) platelets, and neutrophil, lymphocyte, monocyte, eosinophil and basophil counts) and chemistry (alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, alkaline phosphatase (ALP) and Comprehensive Metabolic Panel (CMP)). Complete Blood Count (CBC) with differential and chemistry (ALT, AST, ALP, creatinine and CMP) results were collected at different timepoints throughout the study per the protocol's schedule of evaluations. Institutional laboratory normal ranges as well as the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 were used.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Neutrophil Count	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Alanine aminotransferase (ALT)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Aspartate aminotransferase (AST)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Creatinine	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Number of Participants with one or more Abnormal Laboratory Results AE Related to Study Product	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Number of Participants with one or more Abnormal Laboratory Results AE Unrelated to Study Product	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Laboratory Measures of Safety Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Total Number of Participants who had Any Abnormal Laboratory Results Reported as AEs	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4 and 8 for single dose groups, or Baseline and Weeks 4, 28, and 32 for repeat dose groups

Population: Population included all enrolled participants who received at least one dose of study product with up to 8 weeks of pharmacokinetic data for single dose groups (1-4 and 7-8, N=22) and up to 32 weeks of pharmacokinetic data for repeat dose groups (5-6, N=10). One participant in Group 2 withdrew from the study prior to receiving study product.

A three-tiered assay was used for ADA evaluation. The tier 1 screening assay measures specific and non-specific binding of serum proteins to N6LS. The tier 2 assay is a qualitative competition assay in which exogenously added N6LS removes any N6LS-binding proteins from the serum prior to the binding assay. If the addition of the exogenous N6LS results in a reduction of signal, the specificity of N6LS binding is confirmed. The tier 3 assay is a qualitative assay that assesses the ability of N6LS-binding serum protein to prevent N6LS-mediated neutralization of an HIV pseudovirus in vitro. Only samples positive for a tier were analyzed in subsequent tiers.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Number of Participants Who Produced N6LS Anti-drug Antibodies (ADA) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Tier 1 ADA-Positive Sample	2 Participants	2 Participants	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Produced N6LS Anti-drug Antibodies (ADA) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Tier 2 ADA-Positive Sample	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Produced N6LS Anti-drug Antibodies (ADA) Following N6LS Product Administration Alone or N6LS Co-Administered With rHuPH20 Tier 3 ADA-Positive Sample	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

Population: Population included all enrolled participants who received at least one dose of study product with up to 24 weeks of pharmacokinetic data for single dose groups (1-4 and 7-8, N=22) and up to 48 weeks of pharmacokinetic data for repeat dose groups (5-6, N=10). One participant in Group 2 withdrew from the study prior to receiving study product.

Cmax is the peak serum concentration that N6LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Pharmacokinetic (PK) Parameters of N6LS: Maximum Observed Serum Concentration (Cmax)	109.0 μg/ml Standard Deviation 28.6	20.8 μg/ml Standard Deviation 1.9	492.7 μg/ml Standard Deviation 22.9	737.3 μg/ml Standard Deviation 53.7	21.3 μg/ml Standard Deviation 5.4	411.0 μg/ml Standard Deviation 76.7	37.3 μg/ml Standard Deviation 3.9	108.8 μg/ml Standard Deviation 40.6

SECONDARY outcome

Timeframe: Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

Tmax is the time it takes to reach Cmax of N6LS after it has been administered; it is determined based on the summary PK curve for each dose group.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Pharmacokinetic (PK) Parameters of N6LS: Time to Reach Maximum Observed Serum Concentration (Tmax)	0.12 days Standard Deviation 0.05	2.85 days Standard Deviation 1.02	0.12 days Standard Deviation 0.09	0.13 days Standard Deviation 0.07	6.87 days Standard Deviation 0.07	0.03 days Standard Deviation 0.02	2.56 days Standard Deviation 0.44	4.34 days Standard Deviation 2.38

SECONDARY outcome

Timeframe: Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

Beta half-life (T1/2b) will be reported for this study. Beta half-life (T1/2b) is the time required for half of the N6LS product to be eliminated from the serum.

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Pharmacokinetic (PK) Parameters of N6LS: Beta Half-life (T1/2b)	48.7 days Standard Deviation 3.5	46.8 days Standard Deviation 1.7	50.9 days Standard Deviation 2.3	45.3 days Standard Deviation 4.4	49.9 days Standard Deviation 4.6	46.9 days Standard Deviation 1.9	49.2 days Standard Deviation 2.0	49.8 days Standard Deviation 6.5

SECONDARY outcome

Timeframe: Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

Clearance is the rate of N6LS elimination divided by the plasma N6LS concentration; determined based on the summary pharmacokinetic (PK) curve for each study group. Clearance following a SC administration is calculated as Clearance (CL)/Bioavailability (F).

Outcome measures

Outcome measures
Measure	Group 1: N6LS (5 mg/kg IV) Single Dose n=3 Participants N6LS (5 mg/kg) administered by intravenous (IV) infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 2: N6LS (5 mg/kg SC) Single Dose n=3 Participants N6LS (5 mg/kg) administered by subcutaneous (SC) injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 3: N6LS (20 mg/kg IV) Single Dose n=3 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 4: N6LS (40 mg/kg IV) Single Dose n=3 Participants N6LS (40 mg/kg) administered by IV infusion (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 5: N6LS (5 mg/kg SC) Repeat Dose n=5 Participants N6LS (5 mg/kg) administered by SC injection (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 6: N6LS (20 mg/kg IV) Repeat Dose n=5 Participants N6LS (20 mg/kg) administered by IV infusion (Day 0, Week 12 and Week 24) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site.	Group 7: N6LS (5 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (5 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.	Group 8: N6LS (20 mg/kg SC) + rHuPH20 (2000 U/ml SC) Single Dose n=5 Participants N6LS (20 mg/kg) + rHuPH20 (2000 U/ml) administered by SC injection (Day 0) VRC-HIVMAB091-00-AB: N6LS (VRC-HIVMAB091-00-AB) is a human monoclonal antibody targeted to the HIV-1 CD4 binding site. rHuPH20: Recombinant human hyaluronidase PH20 (rHuPH20) is the active ingredient of the investigational ENHANZE™ Drug Product (EDP). EDP is a purified preparation of rHuPH20.
Pharmacokinetic (PK) Parameters of N6LS: Clearance Rate	143.1 ml/day Standard Deviation 35.1	365.3 ml/day Standard Deviation 108.5	142.3 ml/day Standard Deviation 13.3	131.0 ml/day Standard Deviation 22.7	297.6 ml/day Standard Deviation 60.3	148.3 ml/day Standard Deviation 28.3	205.9 ml/day Standard Deviation 16.8	253.7 ml/day Standard Deviation 102.0

SECONDARY outcome

Timeframe: Baseline through the study participation, up to Week 24 for single dose groups and up to Week 48 for repeat dose groups

Theoretical volume that would be necessary to contain the total amount of administered drug at the same concentration as observed in plasma. It represents the degree to which a drug is distributed in body tissue rather than the plasma and calculated based in the PK curve for each study group. Volume of distribution following a SC administration is calculated as Volume of distribution (V)/Bioavailability (F).