VRC 605: Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered Intravenously or Subcutaneously to Healthy Adults

Unsolicited adverse events (AEs) collected during the period from study product administration at Day 0 through 56 days after the last product administration. After the indicated time period through the last expected study visit at 24 weeks after the last product administration, only new chronic medical conditions collected as unsolicited AEs. The number reported is the number of subjects who experienced at least one AE in the reporting period. A subject with multiple experiences of the same event is counted once using the event of worst severity.

Time frame: Through 24 weeks after the last product administration

Population: Subjects who received VRC07-523LS (N=25), where N signifies number of subjects analyzed for this outcome measure.

Local symptoms assessed and recorded by the clinicians. Solicited local symptoms include pain/tenderness, swelling, redness, bruising, and pruritus (itchiness) at the product administration site. Clinicians assessed the study product administration site for local symptoms on the day of product administration after completion of the administration and on Days 1, 2 and 7 post administration. Subjects were counted once for each symptom at the worst severity if they experienced the symptom at any severity during the reporting period. If symptoms were experienced, clinicians collected resolution information for any symptom that was not resolved within 7 days. The number reported for Any Local Symptom is the number of subjects reporting any local symptom at the worst severity. Solicited reactogenicity recorded without an attribution assessment. If symptoms were reported, grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.

Time frame: 7 days after each product administration

Population: Subjects who received VRC07-523LS (N=25), where N signifies number of subjects analyzed for this outcome measure. Groups 1, 2, 4, 5 and 7 are IV administration groups and Groups 3 and 6 are SC administration groups, with Groups 6 and 7 receiving multiple doses.

Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the last product administration.

Time frame: Through 24 weeks after the last product administration

Population: Subjects who received VRC07-523LS (N=25), where N signifies number of subjects analyzed for this outcome measure.

Subjects recorded 3-day systemic symptoms in a diary after each study product administration. Solicited systemic symptoms include: unusually tired/feeling unwell, muscles aches, headache, chills, nausea, temperature and joint pain. Subjects recorded highest measured temperature daily. Clinicians reviewed the diary with the subject and collected resolution information for any symptoms that were not resolved within 3 days. Subjects were counted once for each symptom at the worst severity if they indicated experiencing the symptom at any severity during the reporting period. The number reported for Any Systemic Symptom is the number of subjects reporting any systemic symptom at the worst severity. Solicited reactogenicity was recorded without an attribution assessment. Grading was done by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Version 2.0.

Time frame: 3 days after each product administration

Population: Subjects who received VRC07-523LS (N=25), where N signifies number of subjects analyzed for this outcome measure. Groups 1, 2, 4, 5 and 7 are IV administration groups and Groups 3 and 6 are SC administration groups, with Groups 6 and 7 receiving multiple doses.

The mean of individual subject VRC07-523LS serum concentrations by administered dose group

Time frame: Up to 12 weeks after each product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV). For Dose 3, values calculated from 4 subjects per group.

The mean of individual subject VRC07-523LS serum concentrations by administered dose group

Time frame: Week 12 post product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV).

The mean of individual subject VRC07-523LS serum concentrations by administered dose group

Time frame: Week 4 post product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV).

The AUC0-84D represents the total drug exposure in 84 days after VRC07-523LS administration; it is determined based on the summary PK curve for each group. Serum was collected at the following time points for Groups 6 and 7 after Dose 1 and Dose 3: Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 6, Dose 3: Pre-injection (Week 24) and 72 hours post injection, followed by Weeks 25-28 and every 4 weeks up to 48 weeks post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hrs post infusion, followed by Weeks 1, 2, 4 and 8 post infusion; Group 7, Dose 3: Pre-infusion (Week 24), end of infusion and 1 hour post infusion followed by Weeks 25-28 and every 4 weeks up to 48 weeks post infusion

Time frame: Administration (0h) up to 84 days after each product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV). For Dose 3, value calculated from 4 subjects per group.

The total area under the curve (AUC(inf)) was taken as the sum of the observed AUC up to the final concentration (AUC(obs)) plus the AUC after the final concentration (AUC(Clast-inf)) where AUC(Clast-inf) was estimated as Clast/lz. Serum was collected at the following time points: Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4, 8, 12, 16, 20, and 24 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4, 8, 12, 16, 20, and 24 post injection

Time frame: Administration (0h) to 24 weeks post product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV).

Cmax is the peak serum concentration that VRC07-523LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group. Serum was collected at the following time points for Groups 6 and 7 after Dose 1 and Dose 3: Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 6, Dose 3: Pre-injection (Week 24) and 72 hours post injection, followed by Weeks 25-28 and every 4 weeks up to 48 weeks post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hrs post infusion, followed by Weeks 1, 2, 4 and 8 post infusion; Group 7, Dose 3: Pre-infusion (Week 24), end of infusion and 1 hour post infusion followed by Weeks 25-28 and every 4 weeks up to 48 weeks post infusion

Time frame: Through 24 weeks after the last product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV). For Dose 3, values calculated from 4 subjects per group.

Cmax is the peak serum concentration that VRC07-523LS achieves after it has been administered; it is determined as a maximum value on the summary pharmacokinetic (PK) curve for each study group. Serum was collected at the following time points: Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4, 8, 12, 16, 20, and 24 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4, 8, 12, 16, 20, and 24 post injection

Time frame: Up to 24 weeks post product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV).

Serum samples collected 4 weeks, 28 weeks and 32 weeks after VRC07-523LS administration

Time frame: Weeks 4, 28 and 32 after the first product administration

Population: Subjects who received multiple doses of VRC07-523LS via SC or IV administration. One subject in Group 7 who only received a single dose was not included in this analysis but was analyzed with Group 4 (single dose at 20 mg/kg IV).

Serum samples collected 4 weeks and 8 weeks after VRC07-523LS administration

Time frame: Weeks 4 and 8 post product administration

Population: Subjects who received a single dose of VRC07-523LS via SC or IV administration. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4.

Half-life (T1/2) is the time required for half of the drug to be eliminated from the serum. Serum was collected at the following time points: Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4 and 8 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4 and 8 post injection; Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1, 2, 4 and 8 post infusion

Time frame: Administration (0h) to 56 days post product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV).

Tmax is the time it takes to reach Cmax of VRC07-523LS after it has been administered; it is determined based on the summary PK curve for each study group Serum was collected at the following time points: Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4, 8, 12, 16, 20, and 24 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4, 8, 12, 16, 20, and 24 post injection; Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2, 4 and 8 post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1, 2, 4 and 8 post infusion

Time frame: 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

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS, and represents the first dose only. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV).

Rate of VRC07-523LS elimination divided by the plasma VRC07-523LS concentration; determined based on the summary PK curve for each study group. Serum was collected at the following time points: Groups 1, 2, 4, and 5: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1-4 post infusion; Group 3: Pre-injection (baseline) and 24, 48, 72 hours post injection, and Weeks 1-4 post injection; Group 6, Dose 1: Pre-injection (baseline) and 24, 48, and 72 hours post injection, followed by Weeks 1, 2 and 4 post injection; Group 7, Dose 1: Pre-infusion (baseline), end of infusion (0h) and 1, 3, 6, 24 and 48 hours post infusion, followed by Weeks 1, 2 and 4 post infusion

Time frame: Administration (0h) to 28 days post product administration

Population: Pharmacokinetic (PK) parameters shown for all subjects who received at least one administration of VRC07-523LS. One subject in Group 7 (multiple doses at 20 mg/kg IV) who only received a single dose was analyzed with Group 4 (single dose at 20 mg/kg IV). Value following SC administration represents CL/F (apparent clearance).