A Phase 1 interventional study of VRC-HIVMAB075-00-AB in HIV Prevention, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2020-10-26.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention
Background:
Human immunodeficiency virus (HIV) is a global health threat. The body uses antibodies to fight infection. VRC07-523LS is an antibody directed against HIV. It may be used to prevent mother-to-child transmission of HIV. It may also prevent sexual transmission of HIV and treat HIV-1 infected people.
Objective:
To test the safety, tolerability, dose, and pharmacokinetics of VRC07-523LS in healthy adults.
Eligibility:
Healthy people ages 18-50
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Participants will be assigned to 1 of 7 groups:
Groups 1-5 will get the drug at 1 visit and then be observed for 24 weeks.
Groups 6 and 7 will get the drug at 1 visit every 12 weeks, for a total of 3 doses over 48 weeks.
Participants will get the drug in 1 of 2 ways:
Infusion into a vein over at least 30 minutes. Participants will have blood tests 1, 3, and 6 hours after the infusion. They will have 1-3 visits during that week. Those in Group 7 will have 4-5 visits in the week after their second and third doses.
Injection into the fatty tissue under the skin. Participants will have blood tests before the injection. They will have 1-3 visits during that week. Those in Group 6 will have 4-5 visits after the second and third doses.
Visits include:
Physical exam
Blood and urine tests
Optional oral swabs to collect saliva
Participants will keep a diary of their temperature and symptoms for 3 days after each dose.
This is the first study of the VRC-HIVMAB075-00-AB (VRC07-523LS) monoclonal antibody (MAb) in healthy adults. It is a phase 1, dose-escalation study to examine safety, tolerability, dose, and pharmacokinetics of VRC07-523LS. The hypothesis is that VRC07-523LS will be safe for administration to healthy adults by the intravenous (IV) and subcutaneous (SC) routes.
Healthy adults 18-50 years of age will be enrolled. There are 4 open-label, dose escalations of VRC07-523LS from 1 mg/kg IV to 40 mg/kg IV, 1 route escalation from IV to SC, and 2 open-label groups to assess repeat dosing. Groups 1-5 are expected to include 3 subjects and Groups 6-7 are expected to enroll 5 subjects. Subjects will be followed for 24 weeks after the last study product administration.
National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
A volunteer must meet all of the following criteria:
Screening laboratory values within 84 days prior to enrollment must meet the following criteria:
Female-Specific Criteria:
EXCLUSION CRITERIA:
A volunteer will be excluded if one or more of the following conditions apply:
Group 1 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 1 mg/kg.
Biological: VRC-HIVMAB075-00-AB
Group 2 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 5 mg/kg.
Biological: VRC-HIVMAB075-00-AB
Group 3 subjects received a single SC injection of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 5 mg/kg.
Biological: VRC-HIVMAB075-00-AB
Group 4 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 20 mg/kg.
Biological: VRC-HIVMAB075-00-AB
Group 5 subjects received a single IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0 at a dose of 40 mg/kg.
Biological: VRC-HIVMAB075-00-AB
Group 6 subjects received a SC injection of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0, Week 12 and Week 24 at a dose of 5 mg/kg.
Biological: VRC-HIVMAB075-00-AB
Group 7 subjects received an IV infusion of VRC07-523LS (VRC-HIVMAB075-00-AB) on Day 0, Week 12 and Week 24 at a dose of 20 mg/kg.
Biological: VRC-HIVMAB075-00-AB
VRC07-523LS is an Investigational Monoclonal Antibody targeted to the CD4 binding site of HIV-1.
Also known as: VRC07-523LS
Number of Subjects Reporting Systemic Reactogenicity Signs and Symptoms Within 3 Days of Any Product Administration
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
Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Product Administration
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
Number of Subjects Reporting 1 or More Unsolicited Non-Serious Adverse Events
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
Number of Subjects Reporting Serious Adverse Events
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
Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups
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
Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Multiple Dose Groups
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
Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS
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
4 Week Mean Serum Concentration of VRC07-523LS
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
Time frame: Week 4 post product administration
12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
Time frame: Week 12 post product administration
12 Week Mean Serum Concentration of VRC07-523LS: Multiple Dose Groups
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
Time frame: Up to 12 weeks after each product administration
Area Under the Curve (AUC(0-inf)): Single Dose Groups
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
Area Under the Curve (AUC0-84D): Multiple Dose Groups
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
VRC07-523LS Clearance Rate
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
Overall IV Half-life (T1/2) of VRC07-523LS
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
Number of Single Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
Serum samples collected 4 weeks and 8 weeks after VRC07-523LS administration
Time frame: Weeks 4 and 8 post product administration
Number of Multiple Dose Subjects Who Produced Anti-Drug Antibodies to VRC07-523LS
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
Healthy adults were recruited at the NIH Clinical Center in Bethesda, Maryland.
| Milestone | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|---|---|---|---|---|
| Started | 4 | 3 | 3 | 3 | 3 | 5 | 5 |
| Received vrc07-523ls per protocol | 3 | 3 | 3 | 3 | 3 | 4 | 4 |
| Discontinued vrc07-523ls administrations | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
| Completed | 3 | 3 | 3 | 3 | 3 | 4 | 4 |
| Not completed | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
| Withdrew: Enrolled, but product never administered | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Physician decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
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.
| Participants | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 7: 20 mg/kg IV Multiple Doses: Dose 1 | Group 7: 20 mg/kg IV Multiple Doses: Dose 2 | Group 7: 20 mg/kg IV Multiple Doses: Dose 3 | Overall IV Groups | Group 3: 5 mg/kg SC Single Dose | Group 6: 5 mg/kg SC Multiple Doses: Dose 1 | Group 6: 5 mg/kg SC Multiple Doses: Dose 2 | Group 6: 5 mg/kg SC Multiple Doses: Dose 3 | Overall SC Groups |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Malaise — None | 3 | 3 | 3 | 2 | 3 | 3 | 3 | 14 | 3 | 2 | 4 | 4 | 5 |
| Malaise — Mild | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 2 | 0 | 3 | 0 | 0 | 3 |
| Malaise — Moderate | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Myalgia — None | 3 | 2 | 3 | 2 | 4 | 3 | 3 | 14 | 3 | 3 | 4 | 4 | 6 |
| Myalgia — Mild | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 2 | 0 | 2 | 0 | 0 | 2 |
| Myalgia — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Headache — None | 3 | 3 | 3 | 2 | 4 | 3 | 4 | 15 | 3 | 3 | 3 | 4 | 5 |
| Headache — Mild | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 2 | 0 | 2 | 1 | 0 | 3 |
| Headache — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Chills — None | 3 | 3 | 3 | 2 | 4 | 3 | 3 | 15 | 3 | 4 | 4 | 4 | 7 |
| Chills — Mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Chills — Moderate | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
| Nausea — None | 3 | 3 | 3 | 2 | 5 | 4 | 4 | 16 | 3 | 4 | 4 | 4 | 7 |
| Nausea — Mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Nausea — Moderate | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Temperature — None | 3 | 3 | 3 | 3 | 4 | 4 | 4 | 16 | 3 | 5 | 4 | 4 | 8 |
| Temperature — Mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Temperature — Moderate | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Joint Pain — None | 3 | 3 | 3 | 2 | 5 | 4 | 3 | 15 | 3 | 3 | 4 | 4 | 6 |
| Joint Pain — Mild | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 2 |
| Joint Pain — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| Any Systemic Symptom Reported — None | 3 | 2 | 3 | 2 | 3 | 3 | 3 | 13 | 3 | 1 | 3 | 4 | 3 |
| Any Systemic Symptom Reported — Mild | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 4 | 1 | 0 | 5 |
| Any Systemic Symptom Reported — Moderate | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
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.
| Participants | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 7: 20 mg/kg IV Multiple Doses: Dose 1 | Group 7: 20 mg/kg IV Multiple Doses: Dose 2 | Group 7: 20 mg/kg IV Multiple Doses: Dose 3 | Overall IV Groups | Group 3: 5 mg/kg SC Single Dose | Group 6: 5 mg/kg SC Multiple Doses: Dose 1 | Group 6: 5 mg/kg SC Multiple Doses: Dose 2 | Group 6: 5 mg/kg SC Multiple Doses: Dose 3 | Overall SC Groups |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pain/Tenderness — None | 3 | 3 | 2 | 3 | 5 | 4 | 4 | 16 | 2 | 2 | 1 | 2 | 4 |
| Pain/Tenderness — Mild | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 3 | 3 | 2 | 4 |
| Pain/Tenderness — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Bruising — None | 3 | 3 | 3 | 3 | 4 | 4 | 4 | 16 | 3 | 5 | 4 | 4 | 8 |
| Bruising — Mild | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Bruising — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Swelling — None | 3 | 3 | 3 | 3 | 5 | 4 | 4 | 17 | 3 | 5 | 4 | 4 | 8 |
| Swelling — Mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Swelling — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Redness — None | 3 | 3 | 3 | 3 | 5 | 4 | 4 | 17 | 3 | 5 | 4 | 3 | 7 |
| Redness — Mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Redness — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Pruritus — None | 3 | 3 | 3 | 3 | 5 | 4 | 4 | 17 | 3 | 5 | 4 | 4 | 8 |
| Pruritus — Mild | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pruritus — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Any Local Symptom Reported — None | 3 | 3 | 2 | 3 | 4 | 4 | 4 | 15 | 2 | 2 | 1 | 1 | 4 |
| Any Local Symptom Reported — Mild | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 1 | 3 | 3 | 2 | 3 |
| Any Local Symptom Reported — Moderate | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
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.
| Participants | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Overall |
|---|---|---|---|---|---|---|---|---|
| Related to study product | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 4 |
| Unrelated to study product | 2 | 1 | 1 | 0 | 0 | 5 | 3 | 12 |
Serious adverse events (SAEs) collected during the period from study product administration at Day 0 through 24 weeks after the last product administration.
| Participants | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Overall |
|---|---|---|---|---|---|---|---|---|
| Related to study product | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unrelated to study product | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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
| µg/mL | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose |
|---|---|---|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of VRC07-523LS: Single Dose Groups | 47 ± 16 | 240 ± 35 | 50 ± 11 | 869 ± 190 | 1630 ± 644 |
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
| µg/mL | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|
| Dose 1 | 38 ± 17 | 1196 ± 74 |
| Dose 3 | 37 ± 12 | 799 ± 98 |
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
| days | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|---|---|---|---|---|
| Time to Reach Maximum Observed Serum Concentration (Tmax) of VRC07-523LS | 0.7 ± 0.5 | 0.04 ± 0.02 | 10 ± 9.5 | 0.3 ± 0.4 | 0.04 ± 0.02 | 5.7 ± 5.0 | 0.04 ± 0.02 |
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
| µg/mL | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|---|---|---|---|---|
| 4 Week Mean Serum Concentration of VRC07-523LS | 14 ± 7.5 | 57 ± 11 | 31 ± 11 | 148 ± 28 | 272 ± 52 | 25 ± 13 | 242 ± 51 |
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
| µg/mL | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose |
|---|---|---|---|---|---|
| 12 Week Mean Serum Concentration of VRC07-523LS: Single Dose Groups | 3.8 ± 0.7 | 57 ± 11 | 7.1 ± 1.3 | 44 ± 14 | 85 ± 30 |
The mean of individual subject VRC07-523LS serum concentrations by administered dose group
| µg/mL | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|
| Dose 1 | 6.3 ± 1.5 | 46 ± 13 |
| Dose 3 | 9.8 ± 2.5 | 71 ± 29 |
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
| µg*d/mL | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose |
|---|---|---|---|---|---|
| Area Under the Curve (AUC(0-inf)): Single Dose Groups | 1381 ± 325 | 4551 ± 904 | 2189 ± 309 | 13748 ± 1853 | 25517 ± 5097 |
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
| µg*d/mL | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|
| Dose 1 | 1440 ± 563 | 14760 ± 2646 |
| Dose 3 | 1671 ± 443 | 13573 ± 1115 |
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
| mL/day | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 7: 20 mg/kg IV Multiple Doses | Overall IV Groups | Group 3: 5 mg/kg SC Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Overall SC Groups |
|---|---|---|---|---|---|---|---|---|---|
| VRC07-523LS Clearance Rate | 70 ± 20 | 78 ± 18 | 110 ± 19 | 105 ± 14 | 101 ± 15 | 94 ± 22 | 226 ± 54 | 158 ± 34 | 184 ± 52 |
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
| days | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 7: 20 mg/kg IV Multiple Doses | Overall IV Groups | Group 3: 5 mg/kg SC Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Overall SC Groups |
|---|---|---|---|---|---|---|---|---|---|
| Overall IV Half-life (T1/2) of VRC07-523LS | 48 ± 26 | 32 ± 1.1 | 45 ± 5.2 | 42 ± 5.1 | 27 ± 1.8 | 38 ± 12 | 36 ± 6.7 | 31 ± 10 | 33 ± 8.9 |
Serum samples collected 4 weeks and 8 weeks after VRC07-523LS administration
| Participants | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose |
|---|---|---|---|---|---|
| Week 4: Subjects with Anti-Drug Antibodies | 0 | 0 | 0 | 0 | 0 |
| Week 8: Subjects with Anti-Drug Antibodies | 0 | 0 | 0 | 0 | 0 |
Serum samples collected 4 weeks, 28 weeks and 32 weeks after VRC07-523LS administration
| Participants | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses |
|---|---|---|
| Week 4: Subjects with Anti-Drug Antibodies | 0 | 0 |
| Week 28: Subjects with Anti-Drug Antibodies | 0 | 0 |
| Week 32: Subjects with Anti-Drug Antibodies | 0 | 0 |
Collected over Solicited adverse events (AEs) included systemic AEs reported by subjects at the worst severity through 3 days post any product administration; and local administration site AEs reported for subjects at the worst severity through 7 days post any product administration. Unsolicited AEs were reported from the date of product administration through 56 days thereafter, and new chronic medical conditions and SAEs with onset any time following the date of last product administration through 24 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group 1: 1 mg/kg IV Single Dose | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) |
| Group 2: 5 mg/kg IV Single Dose | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) |
| Group 4: 20 mg/kg IV Single Dose | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) |
| Group 5: 40 mg/kg IV Single Dose | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) |
| Group 7: 20 mg/kg IV Multiple Doses | 0/5 (0%) | 0/5 (0%) | 5/5 (100%) |
| Group 3: 5 mg/kg SC Single Dose | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) |
| Group 6: 5 mg/kg SC Multiple Doses | 0/5 (0%) | 0/5 (0%) | 5/5 (100%) |
| Event | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 7: 20 mg/kg IV Multiple Doses | Group 3: 5 mg/kg SC Single Dose | Group 6: 5 mg/kg SC Multiple Doses |
|---|---|---|---|---|---|---|---|
| Upper respiratory tract infectionInfections and infestations | 0/3 | 1/3 | 0/3 | 0/3 | 2/5 | 0/3 | 3/5 |
| HypernatraemiaMetabolism and nutrition disorders | 1/3 | 0/3 | 0/3 | 0/3 | 3/5 | 0/3 | 2/5 |
| Administration site pain/tendernessGeneral disorders | 0/3 | 0/3 | 1/3 | 0/3 | 0/5 | 1/3 | 3/5 |
| MalaiseGeneral disorders | 0/3 | 0/3 | 0/3 | 1/3 | 2/5 | 0/3 | 3/5 |
| HeadacheNervous system disorders | 0/3 | 0/3 | 0/3 | 1/3 | 1/5 | 0/3 | 3/5 |
| Muscle strainInjury, poisoning and procedural complications | 0/3 | 0/3 | 0/3 | 0/3 | 2/5 | 0/3 | 0/5 |
| MyalgiaMusculoskeletal and connective tissue disorders | 0/3 | 1/3 | 0/3 | 1/3 | 1/5 | 0/3 | 2/5 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/3 | 0/3 | 0/3 | 1/3 | 1/5 | 0/3 | 2/5 |
| HaemorrhoidsGastrointestinal disorders | 1/3 | 0/3 | 0/3 | 0/3 | 0/5 | 0/3 | 0/5 |
| Viral infectionInfections and infestations | 0/3 | 0/3 | 0/3 | 1/3 | 0/5 | 0/3 | 0/5 |
Population includes all enrolled subjects.
| Age, Continuous(years) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 26.5 ± 7.0 | 28.0 ± 9.5 | 30.0 ± 7.0 | 27.0 ± 2.6 | 40.0 ± 10.4 | 25.8 ± 4.1 | 30.0 ± 10.6 | 29.2 ± 8.1 |
| Age, Customized(Participants) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| 21-30 years | 3 | 2 | 2 | 3 | 1 | 4 | 3 | 18 |
| 31-40 years | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 5 |
| 41-50 years | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 3 |
| Sex: Female, Male(Participants) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 2 | 2 | 0 | 1 | 3 | 5 | 2 | 15 |
| Male | 2 | 1 | 3 | 2 | 0 | 0 | 3 | 11 |
| Ethnicity (NIH/OMB)(Participants) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 4 |
| Not Hispanic or Latino | 4 | 3 | 2 | 2 | 2 | 4 | 5 | 22 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| Asian | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 3 |
| Black or African American | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 3 |
| White | 2 | 2 | 2 | 2 | 1 | 4 | 3 | 16 |
| Multiracial | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 4 |
| Weight(kg) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 75.8 ± 4.6 | 65.5 ± 17.3 | 89.4 ± 15.0 | 75.9 ± 11.0 | 67.2 ± 20.1 | 55.2 ± 7.1 | 76.1 ± 11.4 | 71.3 ± 14.9 |
| Education(Participants) | Group 1: 1 mg/kg IV Single Dose | Group 2: 5 mg/kg IV Single Dose | Group 3: 5 mg/kg SC Single Dose | Group 4: 20 mg/kg IV Single Dose | Group 5: 40 mg/kg IV Single Dose | Group 6: 5 mg/kg SC Multiple Doses | Group 7: 20 mg/kg IV Multiple Doses | Total |
|---|---|---|---|---|---|---|---|---|
| High school graduate/GeneralEducationalDevelopment | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
| College/University | 2 | 2 | 2 | 2 | 2 | 4 | 4 | 18 |
| Advanced degree | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 6 |
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