HIV Infections
Conditions
Brief summary
The purpose of this study was to assess the safety and pharmacokinetics (PK) of three monoclonal antibodies, VRC01, VRC01LS, and VRC07-523LS, in HIV-exposed infants who are at increased risk of mother-to-child HIV transmission.
Detailed description
VRC01, VRC01LS, and VRC07-523LS are anti-HIV neutralizing monoclonal antibodies that may help prevent mother-to-child transmission of HIV. This study enrolled HIV-infected mothers who were at increased risk of passing HIV on to their children. The purpose of this study was to assess the safety and PK of VRC01, VRC01LS, and VRC07-523LS in HIV-exposed infants. This study enrolled mother-infant pairs into five dose groups. Infants enrolled in Dose Group 1 and Dose Group 2 received a single VRC01 injection less than 72 hours after birth. Infants in Dose Group 3 received a VRC01 injection less than 5 days after birth, followed by VRC01 injections monthly for at least 6 months and no more than 18 months, while breastfeeding. Dose Groups 4 and 5 each enrolled infants into two cohorts: Cohort 1 (non-breastfeeding) or Cohort 2 (breastfeeding). Infants in Dose Group 4, Cohort 1 received a single VRC01LS injection less than 72 hours after birth. Infants in Dose Group 4, Cohort 2 received an initial VRC01LS injection no longer than 5 days after birth, and a second VRC01LS injection at Week 12 if they were still breastfeeding. Infants in Dose Group 5, Cohort 1 received a single VRC07-523LS injection less than 72 hours after birth. Infants in Dose Group 5, Cohort 2 received an initial VRC07-523LS injection no longer than 5 days after birth, and a second VRC07-523LS injection at Week 12 if they were still breastfeeding. The mothers did not receive any VRC01, VRC01LS, or VRC07-523LS injections. At study entry, all mothers underwent a medical history review and a blood collection, and then the study ended for the mothers. Infants in Dose Groups 1 and 2 attended study visits at days 0, 1, 3, 7, 14, 28 and at weeks 8, 16, 24, and 48. Infants in Dose Group 3 attended study visits at days 0, 1, 14, 28 and at weeks 8, 12, 16, 20, 24, and every 4 weeks until cessation of breastfeeding or week 72, then at weeks 84 and 96. Infants in Dose Group 4 attended study visits at days 0, 1, 14, 28 and at weeks 8, 12, 24, 36, 48, 60, 72, 84 and 96, with additional visits at weeks 14 and 16 for Cohort 2 participants. Infants in Dose Group 5 attended study visits at days 0, 1, 3, 7, 14, 28 and at weeks 8, 12, 24, 36, 48, 60, 72, 84 and 96, with additional visits at weeks 14 and 16 for Cohort 2 participants. Visits included a medical history review, physical examination, blood collection, and oral fluid collection.
Interventions
BIOLOGICALVRC01
Administered by subcutaneous injection in the thigh
BIOLOGICALVRC01LS
Administered by subcutaneous injection in the thigh
BIOLOGICALVRC07-523LS
Administered by subcutaneous injection in the thigh
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Days to 5 Days
Healthy volunteers
No
Inclusion criteria
Maternal Inclusion Criteria: * HIV infection * Greater than or equal to 18 years of age * Able and willing to provide signed informed consent for herself and her infant Maternal
Exclusion criteria
* Prior participation in any HIV-1 vaccine trial * Receipt of any other active or passive HIV immunotherapy or investigational product during this pregnancy. (Note that administration of Food and Drug Administration \[FDA\]-approved antiretroviral (ARV) drugs when used to treat disease or prevent mother-to-child transmission were not considered investigational.) * Documented or suspected serious medical illness or immediate life-threatening condition (other than HIV infection) in the mother that may have interfered with the ability to complete study requirements, as judged by the examining clinician Infant Inclusion Criteria: * Born to an HIV-1-infected woman who met all maternal inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died | From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.) | The Overall Number of Participants Analyzed represents infants. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Deaths from day 0 to 4 weeks after the participants' last immunization were included. |
| Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.) | The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Adverse events from day 0 to 4 weeks after the participants' last immunization were included. |
| Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.) | The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. The study sites assessed and determined if AEs were related to study treatment. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Adverse events from day 0 to 4 weeks after the participants' last immunization were included. |
| Percentage of Participants Diagnosed With HIV Infection | From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.) | The Overall Number of Participants Analyzed represents infants. Diagnosis testing was performed using a HIV-1 NAT (nucleic acid testing) by a method that detects DNA. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. HIV diagnoses from day 0 to 4 weeks after the participants' last immunization were included. |
| Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4 | Dose Groups (DG) 1, 2: at days 0, 1, 3, 7, 14, 28; DG 3: at days 0, 1, 14, 28, weeks 16, 20, 24; DG 4-Cohort 1: at days 0, 1, 14, 28; Cohort 2: at days 0, 1, 14, 28, 84. | The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). AUC0-28 days (area-under-the-curve from 0 to 28 days) for Dose Groups 1, 2 and 3 and AUC0-84 days for Dose Group 4, were determined using the linear trapezoidal rule. Median and range were summarized. |
| Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Group 5 | Dose Group 5 - Cohort 1: at days 0, 1, 3, 7, 14, 28; Cohort 2: at days 0, 1, 3, 7, 14, 28, 84. | The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). AUC0-84 days (area-under-the-curve from 0 to 84 days) were determined using the linear trapezoidal rule. Median and range were summarized. |
| Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4 | Dose Groups (DG) 1, 2: at days 0, 1, 3, 7, 14, 28; DG 3: at days 0, 1, 14, 28, weeks 16, 20, 24; DG 4-Cohort 1: at days 0, 1, 14, 28; Cohort 2: at days 0, 1, 14, 28, 84. | The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). Median and range were summarized for C28 days (concentration at 28 days) for Dose Groups 1, 2 and 3 and C84 days for Dose Group 4. |
| Pharmacokinetics (PK) Parameter: Concentration for Dose Group 5 | Dose Group 5 - Cohort 1: at days 0, 1, 3, 7, 14, 28; Cohort 2: at days 0, 1, 3, 7, 14, 28, 84. | The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). Median and range were summarized for C84 days (concentration at 84 days). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Group 3 and 4). | The Overall Number of Participants Analyzed represents infants. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here. |
| Number of Participants Who Developed Anti-VRC Antibodies | At weeks 24 and 48. | The Overall Number of Participants Analyzed represents infants with samples collected and tested. The number of infants who developed anti antibodies to the study products are summarized. For Dose Groups 1, 2, and 3, these are anti-VRC01 antibodies. For Dose Group 4, these are anti-VCR07 antibodies and for Dose Group 5, these are anti-VRC07-523LS antibodies. |
| Percentage of Participants Who Died After Last Immunization for Dose Group 5 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5). | The Overall Number of Participants Analyzed represents infants. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. |
| Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Groups 3 and 4). | The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here. |
| Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Group 5 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5). | The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. |
| Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Groups 3 and 4). | The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. The study sites assessed if AEs were related to study treatment. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here. |
| Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Group 5 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5). | The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. The study sites assessed if AEs were related to study treatment. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. |
| Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Groups 3 and 4). | The Overall Number of Participants Analyzed represents infants. Diagnosis testing was performed using a HIV-1 NAT (nucleic acid testing) by a method that detects DNA. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here. |
| Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Group 5 | From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5). | The Overall Number of Participants Analyzed represents infants. Diagnosis testing was performed using a HIV-1 NAT (nucleic acid testing) by a method that detects DNA. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. |
Countries
Puerto Rico, South Africa, United States, Zimbabwe
Participant flow
Recruitment details
83 mother-infant pairs were enrolled in the study. Since the mothers did not receive any treatment on study and were taken off study immediately after enrollment, the number of participants shown in all tables is the number of infants (83). Participants were enrolled from June 2015 to February 2020, at 14 medical clinics in the United States, Puerto Rico, South Africa and Zimbabwe.
Pre-assignment details
Dose groups enrolled sequentially. There was no randomization.
Participants by arm
| Arm | Count |
|---|---|
| Dose Group 1 Infants in Dose Group 1 received a single VRC01 20 mg/kg injection less than 72 hours after birth.
VRC01: Administered by subcutaneous injection in the thigh | 13 |
| Dose Group 2 Infants in Dose Group 2 received a single VRC01 40 mg/kg injection less than 72 hours after birth.
VRC01: Administered by subcutaneous injection in the thigh | 14 |
| Dose Group 3 Infants in Dose Group 3 received a VRC01 40 mg/kg injection less than 5 days after birth. They then received a VRC01 20 mg/kg injection monthly for at least 6 months and no more than 18 months while breastfeeding.
VRC01: Administered by subcutaneous injection in the thigh | 13 |
| Dose Group 4, Cohort 1 Infants in Cohort 1 received a single VRC01LS injection less than 72 hours after birth. Dose was based on weight: 80 mg for infants weighing less than 4.5 kg and 100 mg for infants weighing 4.5 kg or greater.
VRC01LS: Administered by subcutaneous injection in the thigh | 10 |
| Dose Group 4, Cohort 2 Infants in Cohort 2 received an initial VRC01LS injection no longer than 5 days after birth. Dose was based on weight: 80 mg for infants weighing less than 4.5 kg and 100 mg for infants weighing 4.5 kg or greater. A second dose of 100 mg VRC01LS was administered at Week 12 if an infant was still breastfeeding.
VRC01LS: Administered by subcutaneous injection in the thigh | 11 |
| Dose Group 5, Cohort 1 Infants in Cohort 1 received a single VRC07-523LS injection less than 72 hours after birth. Dose was based on weight: 80 mg for infants weighing less than 4.5 kg and 100 mg for infants weighing 4.5 kg or greater.
VRC07-523LS: Administered by subcutaneous injection in the thigh | 11 |
| Dose Group 5, Cohort 2 Infants in Cohort 2 received an initial VRC07-523LS injection no longer than 5 days after birth. Dose was based on weight: 80 mg for infants weighing less than 4.5 kg and 100 mg for infants weighing 4.5 kg or greater. A second dose of 100 mg VRC07-523LS was administered at Week 12 if an infant was still breastfeeding.
VRC07-523LS: Administered by subcutaneous injection in the thigh | 11 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 2 | 0 | 4 | 1 |
| Overall Study | Unable to get to clinic | 0 | 2 | 0 | 1 | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Dose Group 1 | Dose Group 2 | Dose Group 3 | Dose Group 4, Cohort 1 | Dose Group 4, Cohort 2 | Dose Group 5, Cohort 1 | Dose Group 5, Cohort 2 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Customized Age at first dose | 2 days | 2 days | 2 days | 2 days | 2 days | 1 days | 4 days | 2 days |
| Birth Weight | 3045 grams | 3160 grams | 2860 grams | 2865 grams | 2920 grams | 2810 grams | 3235 grams | 2920 grams |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 10 Participants | 13 Participants | 9 Participants | 11 Participants | 8 Participants | 11 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 13 Participants | 8 Participants | 11 Participants | 8 Participants | 11 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 6 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 11 Participants |
| Region of Enrollment Puerto Rico | 2 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment South Africa | 1 participants | 5 participants | 10 participants | 3 participants | 5 participants | 0 participants | 7 participants | 31 participants |
| Region of Enrollment United States | 10 participants | 9 participants | 0 participants | 7 participants | 0 participants | 11 participants | 0 participants | 37 participants |
| Region of Enrollment Zimbabwe | 0 participants | 0 participants | 3 participants | 0 participants | 6 participants | 0 participants | 4 participants | 13 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 5 Participants | 4 Participants | 6 Participants | 6 Participants | 3 Participants | 37 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 8 Participants | 6 Participants | 5 Participants | 5 Participants | 8 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 14 | 0 / 13 | 0 / 10 | 0 / 11 | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 13 / 13 | 13 / 14 | 13 / 13 | 9 / 10 | 11 / 11 | 11 / 11 | 10 / 11 |
| serious Total, serious adverse events | 4 / 13 | 1 / 14 | 0 / 13 | 2 / 10 | 0 / 11 | 6 / 11 | 1 / 11 |
Outcome results
Primary
Percentage of Participants Diagnosed With HIV Infection
The Overall Number of Participants Analyzed represents infants. Diagnosis testing was performed using a HIV-1 NAT (nucleic acid testing) by a method that detects DNA. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. HIV diagnoses from day 0 to 4 weeks after the participants' last immunization were included.
Time frame: From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.)
Population: All infant study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
| Dose Group 5, Cohort 1 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
| Dose Group 5, Cohort 2 | Percentage of Participants Diagnosed With HIV Infection | 0 percentage of participants |
Primary
Percentage of Participants Who Died
The Overall Number of Participants Analyzed represents infants. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Deaths from day 0 to 4 weeks after the participants' last immunization were included.
Time frame: From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.)
Population: All infant study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants Who Died | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants Who Died | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants Who Died | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants Who Died | 0 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants Who Died | 0 percentage of participants |
| Dose Group 5, Cohort 1 | Percentage of Participants Who Died | 0 percentage of participants |
| Dose Group 5, Cohort 2 | Percentage of Participants Who Died | 0 percentage of participants |
Primary
Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE)
The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Adverse events from day 0 to 4 weeks after the participants' last immunization were included.
Time frame: From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.)
Population: All infant study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 31 percentage of participants |
| Dose Group 2 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 14 percentage of participants |
| Dose Group 3 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 31 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 10 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 27 percentage of participants |
| Dose Group 5, Cohort 1 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 36 percentage of participants |
| Dose Group 5, Cohort 2 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) | 9 percentage of participants |
Primary
Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE)
The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. The study sites assessed and determined if AEs were related to study treatment. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Adverse events from day 0 to 4 weeks after the participants' last immunization were included.
Time frame: From day 0 to 4 weeks after last immunization (at week 4 for Dose Groups 1, 2, 4-Cohort 1, 5-Cohort 1; at week 16-48 for Dose Group 3; at week 16 for Dose Group 4-Cohort 2, 5-Cohort 2.)
Population: All infant study participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
| Dose Group 5, Cohort 1 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
| Dose Group 5, Cohort 2 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) | 0 percentage of participants |
Primary
Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Group 5
The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). AUC0-84 days (area-under-the-curve from 0 to 84 days) were determined using the linear trapezoidal rule. Median and range were summarized.
Time frame: Dose Group 5 - Cohort 1: at days 0, 1, 3, 7, 14, 28; Cohort 2: at days 0, 1, 3, 7, 14, 28, 84.
Population: Participants who received the correct dose and were evaluated for PK at the designated timepoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Group 5 | 5358 mcg*d/mL |
| Dose Group 2 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Group 5 | 4462 mcg*d/mL |
Primary
Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4
The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). AUC0-28 days (area-under-the-curve from 0 to 28 days) for Dose Groups 1, 2 and 3 and AUC0-84 days for Dose Group 4, were determined using the linear trapezoidal rule. Median and range were summarized.
Time frame: Dose Groups (DG) 1, 2: at days 0, 1, 3, 7, 14, 28; DG 3: at days 0, 1, 14, 28, weeks 16, 20, 24; DG 4-Cohort 1: at days 0, 1, 14, 28; Cohort 2: at days 0, 1, 14, 28, 84.
Population: Infants who received the correct dose and were evaluated for PK at the designated timepoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4 | 2672 mcg*d/mL |
| Dose Group 2 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4 | 4435 mcg*d/mL |
| Dose Group 3 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4 | 6654 mcg*d/mL |
| Dose Group 4, Cohort 1 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4 | 9825 mcg*d/mL |
| Dose Group 4, Cohort 2 | Pharmacokinetics (PK) Parameter: Area Under the Curve (AUC) for Dose Groups 1, 2, 3 and 4 | 8639 mcg*d/mL |
Primary
Pharmacokinetics (PK) Parameter: Concentration for Dose Group 5
The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). Median and range were summarized for C84 days (concentration at 84 days).
Time frame: Dose Group 5 - Cohort 1: at days 0, 1, 3, 7, 14, 28; Cohort 2: at days 0, 1, 3, 7, 14, 28, 84.
Population: Participants who received the correct dose and were evaluated for PK at the designated timepoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Pharmacokinetics (PK) Parameter: Concentration for Dose Group 5 | 15.81 mcg/mL |
| Dose Group 2 | Pharmacokinetics (PK) Parameter: Concentration for Dose Group 5 | 19.07 mcg/mL |
Primary
Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4
The Overall Number of Participants Analyzed represents infants. PK parameters were determined from plasma concentration-time profiles using noncompartmental methods (SAS 9.4, Cary, NC). Median and range were summarized for C28 days (concentration at 28 days) for Dose Groups 1, 2 and 3 and C84 days for Dose Group 4.
Time frame: Dose Groups (DG) 1, 2: at days 0, 1, 3, 7, 14, 28; DG 3: at days 0, 1, 14, 28, weeks 16, 20, 24; DG 4-Cohort 1: at days 0, 1, 14, 28; Cohort 2: at days 0, 1, 14, 28, 84.
Population: Infants who received the correct dose and were evaluated for PK at the designated timepoints.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Group 1 | Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4 | 39.19 mcg/mL |
| Dose Group 2 | Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4 | 75.25 mcg/mL |
| Dose Group 3 | Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4 | 124.24 mcg/mL |
| Dose Group 4, Cohort 1 | Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4 | 44.64 mcg/mL |
| Dose Group 4, Cohort 2 | Pharmacokinetics (PK) Parameter: Concentration for Dose Groups 1, 2, 3 and 4 | 49.60 mcg/mL |
Secondary
Number of Participants Who Developed Anti-VRC Antibodies
The Overall Number of Participants Analyzed represents infants with samples collected and tested. The number of infants who developed anti antibodies to the study products are summarized. For Dose Groups 1, 2, and 3, these are anti-VRC01 antibodies. For Dose Group 4, these are anti-VCR07 antibodies and for Dose Group 5, these are anti-VRC07-523LS antibodies.
Time frame: At weeks 24 and 48.
Population: Infant study participants with samples collected and tested.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Group 1 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
| Dose Group 2 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
| Dose Group 3 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
| Dose Group 4, Cohort 1 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
| Dose Group 4, Cohort 2 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
| Dose Group 5, Cohort 1 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
| Dose Group 5, Cohort 2 | Number of Participants Who Developed Anti-VRC Antibodies | 0 Participants |
Secondary
Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Group 5
The Overall Number of Participants Analyzed represents infants. Diagnosis testing was performed using a HIV-1 NAT (nucleic acid testing) by a method that detects DNA. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Group 5 | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Group 5 | 0 percentage of participants |
Secondary
Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4
The Overall Number of Participants Analyzed represents infants. Diagnosis testing was performed using a HIV-1 NAT (nucleic acid testing) by a method that detects DNA. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Groups 3 and 4).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants Diagnosed With HIV Infection After Last Immunization for Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
Secondary
Percentage of Participants Who Died After Last Immunization for Dose Group 5
The Overall Number of Participants Analyzed represents infants. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants Who Died After Last Immunization for Dose Group 5 | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants Who Died After Last Immunization for Dose Group 5 | 0 percentage of participants |
Secondary
Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4
The Overall Number of Participants Analyzed represents infants. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Group 3 and 4).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants Who Died After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
Secondary
Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Group 5
The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Group 5 | 18 percentage of participants |
| Dose Group 2 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Group 5 | 27 percentage of participants |
Secondary
Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4
The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Groups 3 and 4).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4 | 23 percentage of participants |
| Dose Group 2 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4 | 20 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants With an Occurrence of at Least One Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Groups 1, 2, 3 and 4 | 18 percentage of participants |
Secondary
Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Group 5
The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. The study sites assessed if AEs were related to study treatment. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 96 for Dose Group 5).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Group 5 | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization for Dose Group 5 | 0 percentage of participants |
Secondary
Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4
The Overall Number of Participants Analyzed represents infants. AE severity grading was based on the Division of AIDS (DAIDS) AE Grading table, Corrected Version 2.1. The study sites assessed if AEs were related to study treatment. Two-sided 90% exact Clopper-Pearson confidence intervals (CI) were calculated. Data for Dose Groups 1, 2, 3 and 4 are presented here.
Time frame: From four weeks after the participants' last immunization to the end of the study follow-up (at week 48 for Dose Groups 1 and 2 and at week 96 for Dose Groups 3 and 4).
Population: All infants enrolled in these Dose Groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 2 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 3 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 1 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |
| Dose Group 4, Cohort 2 | Percentage of Participants With at Least One VRC01-, VRC01LS-, or VRC07-523LS-related Grade 3 or Higher Adverse Event (AE) After Last Immunization For Dose Groups 1, 2, 3, and 4 | 0 percentage of participants |