COVID-19
Conditions
Keywords
COVID-19, Pregnancy
Brief summary
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study. The objectives of this study were to describe the pharmacokinetic (PK) properties and safety of remdesivir (RDV) administered intravenously as part of clinical care among hospitalized pregnant and non-pregnant women of childbearing potential with coronavirus disease of 2019 (COVID-19). RDV was provided and managed by the participant's treating physician and was not provided as part of this study.
Detailed description
IMPAACT 2032 was a Phase IV prospective, open label, non-randomized opportunistic study to evaluate the PK and safety of RDV when administered to pregnant and non-pregnant women of childbearing potential for treatment of COVID-19. Participants were pregnant and non-pregnant women hospitalized for COVID-19 who received daily RDV infusions, typically for 5 days but in some cases for up to 10 days, as part of their clinical care. RDV was provided and managed by the participants' treating physician and was not provided as a part of this study. This study was comprised of two population-based arms: Arm 1 included pregnant women of any gestational age (GA) and Arm 2 included non-pregnant women of childbearing potential, who were between 18 and 45 years of age. The target sample size was 20 PK-evaluable participants per arm. Study sites were located in the United States. Study procedures for this study were limited to data collection and blood specimens for PK. Except for PK sampling, study procedures were largely done via medical chart abstraction or remote contact/telemedicine visit. Collection of clinical and laboratory data started at 48 hours before the first infusion and continued through 4 weeks after the last infusion. In addition, data were collected at the time of delivery for participants in Arm 1, and limited data were also collected from the birth and newborn exam records of their infants. All participants were followed for safety through 4 weeks after the last infusion; Arm 1 participants who were still pregnant at that time had an additional follow-up at the time of delivery. If there was a gap in time between 4 weeks after the last infusion and delivery, no data were collected during that interval. No formal statistical comparisons were made between Arm 1 and Arm 2 for primary and secondary objectives. Therefore, all analyses for primary and secondary outcome measures represent single arm evaluations.
Interventions
DRUGRemdesivir
RDV was not provided as part of the study. Participants were administered RDV intravenously once daily for up to 10 days per clinical care.
Sponsors
Gilead Sciences
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
Arm 1 (Pregnant Women) * Of legal age or otherwise able to provide independent informed consent or is unable to provide informed consent (e.g., impaired capacity) and a Legally Authorized Representative (LAR) is willing and able to provide written informed consent on behalf of the participant * At study entry, viable intra-uterine pregnancy of any gestational age, based on medical records. * At study entry, hospitalized AND has confirmed or suspected COVID-19, based on medical records. * At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as prescribed by the clinical care provider and documented in medical records. Inclusion Criteria - Arm 2 (Non-Pregnant Women) * Of legal age or otherwise able to provide independent informed consent or is unable to provide informed consent (e.g., impaired capacity) and a Legally Authorized Representative (LAR) is willing and able to provide written informed consent on behalf of the participant * At study entry, between 18 and 45 years of age, based on medical records and participant report. * Assigned female at birth and at study entry not taking cross-sex hormone therapy. * At study entry, not suspected to be pregnant, based on participant report and/or investigator or designee determination. * At study entry, hospitalized AND has confirmed or suspected COVID-19, based on medical records. * At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as prescribed by the clinical care provider and documented in medical records.
Exclusion criteria
* At study entry, has started or received the 4th RDV infusion. * At study entry, evidence of post-menopausal status (medical or surgical), based on medical records and/or participant report. * At study entry, any contraindications to RDV treatment for COVID-19, based on investigator or designee determination. * Received or administered any disallowed medications within 48 hours prior to study entry. * At study entry, has any other condition, that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome: Mean Newborn Head Circumference in Arm 1 | Delivery | We present the newborn mean head circumference among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution. |
| Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1 | First infusion through 7 Days post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term Blood and lymphatic system disorders and high level grouping term Haematology investigations (incl blood groups). The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1 | First infusion through 4 Weeks post-last infusion and Delivery | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher adverse event through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1 | First infusion through 4 Weeks post-last infusion and Delivery | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal serious AE through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 1 | First infusion through 4 Weeks post-last infusion and Delivery | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher AE assessed as related to RDV by the CMC through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1 | Delivery | We present the proportion of participants who had a pregnancy loss at delivery, bounded by an exact 95% confidence interval (CI). |
| Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1 | Delivery | We present the proportion of participants who had a live infant born with congenital anomalies at delivery, bounded by an exact 95% confidence interval (CI). |
| Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1 | Delivery | We present the proportion of participants who had a live preterm birth defined as \< 37 weeks, bounded by an exact 95% confidence interval (CI). |
| Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 34 Weeks in Arm 1 | Delivery | We present the proportion of participants who had a live preterm birth defined as \< 34 weeks, bounded by an exact 95% confidence interval (CI). |
| Safety Outcome: Proportion of Participants With Small for Gestational Age, Defined as < 10th Percentile in Arm 1 | Delivery | We present the proportion of participants who a live born infant who was small for gestational age defined as \< 10th percentile, bounded by an exact 95% confidence interval (CI). |
| Safety Outcome: Mean Newborn Birth Weight in Arm 1 | Delivery | We present the newborn mean weight among the participants who had live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution. |
| Safety Outcome: Mean Newborn Length in Arm 1 | Delivery | We present the newborn mean length among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution. |
| PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1 | At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours. | AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion. |
| PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1 | At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours. | t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion. |
| PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1 | At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours. | GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion. |
| Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1 | First infusion through 7 Days post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term Renal and urinary disorders and high level grouping term Renal and urinary tract investigations and urinalyses. The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1 | First infusion through 7 Days post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term Hepatobiliary disorders and high level grouping term Hepatobiliary investigations. The number of RDV infusions varied by participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 2 | First infusion through 4 Weeks post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one grade 3 or higher AE as related to RDV by the CMC through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant. |
| PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 2 | At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours. | AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion. |
| PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 2 | At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours. | t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion. |
| PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 2 | At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours. | GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion. |
| Safety Outcome: Proportion of Participants With Renal Adverse Event (AE) of Any Grade in Arm 2 | First infusion through 7 Days post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term Renal and urinary disorders and high level grouping term Renal and urinary tract investigations and urinalyses. The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Hepatic Adverse Event (AE) of Any Grade in Arm 2 | First infusion through 7 Days post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term Hepatobiliary disorders and high level grouping term Hepatobiliary investigations. The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Hematologic Adverse Event (AE) of Any Grade in Arm 2 | First infusion through 7 Days post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term Blood and lymphatic system disorders and high level grouping term Haematology investigations (incl blood groups). The number of RDV infusions varied by participant. |
| Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) in Arm 2 | First infusion through 4 Weeks post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one grade 3 or higher AE through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). |
| Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 2 | First infusion through 4 Weeks post-last infusion | Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one serious AE through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant. |
Other
| Measure | Time frame | Description |
|---|---|---|
| PK Outcome: Ratio of Cord Blood/Maternal Plasma Remdisivir (RDV) Concentrations | Delivery | Ratio of cord blood/maternal plasma is calculated for women in Arm 1 who received RDV within 5 days of delivery only. |
| PK Outcome: Ratio of Cord Blood/Maternal Plasma GS-441524 Concentrations | Delivery | GS-441524 is a metabolite of remdesivir (RDV). Ratio of cord blood/maternal plasma is calculated for women in Arm 1 who received RDV within 5 days of delivery only. |
Countries
United States
Participant flow
Recruitment details
Recruitment methods for this study relied on identification of pregnant and non-pregnant women hospitalized for coronavirus disease of 2019 (COVID-19) in a facility that is affiliated with an IMPAACT clinical research site and who recently initiated treatment with remdesivir (RDV) or who may require treatment with RDV. Enrollment occurred between March 31, 2021 and December 29, 2021 across ten sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Pregnant women hospitalized and receiving RDV for treatment of COVID-19.
Remdesivir: RDV was not provided as part of the study. Participants were administered RDV intravenously once daily for up to 10 days per clinical care. | 25 |
| Arm 2 Non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19.
Remdesivir: RDV was not provided as part of the study. Participants were administered RDV intravenously once daily for up to 10 days per clinical care. | 28 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Logistical and Personnel Constraints at Time of Infusion | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 1 | Total | Arm 2 |
|---|---|---|---|
| Age, Continuous | 32.2 years STANDARD_DEVIATION 6.4 | 33.8 years STANDARD_DEVIATION 7 | 35.3 years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 18 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 29 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 22 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) White | 10 Participants | 16 Participants | 6 Participants |
| Region of Enrollment United States | 25 participants | 53 participants | 28 participants |
| Sex: Female, Male Female | 25 Participants | 53 Participants | 28 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 28 |
| other Total, other adverse events | 15 / 25 | 15 / 28 |
| serious Total, serious adverse events | 7 / 25 | 4 / 28 |
Outcome results
Primary
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1
AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Population: Arm 1 women who met the following minimum sampling requirements: (1) at least 3 out of 4 of the end of infusion (EOI) through 3 hours post-end-of-infusion (post-EOI) intensive PK samples AND (2) either the 5 hours post-EOI or the 7 hours post-EOI intensive PK sample AND (3) either the pre-dose or 23-hour post-EOI intensive PK sample, had at least two drug concentrations greater than the lower limit of quantification, and had an available RDV AUC measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 | PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1 | 1246.57 h*ng/mL |
Primary
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1
t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Population: Arm 1 women who met the following minimum sampling requirements: (1) at least 3 out of 4 of the end of infusion (EOI) through 3 hours post-end-of-infusion (post-EOI) intensive PK samples AND (2) either the 5 hours post-EOI or the 7 hours post-EOI intensive PK sample AND (3) either the pre-dose or 23-hour post-EOI intensive PK sample, had at least two drug concentrations greater than the lower limit of quantification, and had an available RDV t1/2 measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 | PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1 | 1.01 hours |
Primary
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1
GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Population: Arm 1 women who met the following minimum sampling requirements: (1) at least 3 out of 4 of the end of infusion (EOI) through 3 hours post-end-of-infusion (post-EOI) intensive PK samples AND (2) either the 5 hours post-EOI or the 7 hours post-EOI intensive PK sample AND (3) either the pre-dose or 23-hour post-EOI intensive PK sample, had at least two drug concentrations greater than the lower limit of quantification, and had an available GS-441524 Ctrough measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 | PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1 | 51.6 ng/mL |
Primary
Safety Outcome: Mean Newborn Birth Weight in Arm 1
We present the newborn mean weight among the participants who had live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Time frame: Delivery
Population: Infants born to Arm 1 women, who received any amount of RDV and had a delivery visit, and had available weight measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 | Safety Outcome: Mean Newborn Birth Weight in Arm 1 | 3.039 kg |
Primary
Safety Outcome: Mean Newborn Head Circumference in Arm 1
We present the newborn mean head circumference among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Time frame: Delivery
Population: Infants born to Arm 1 women, who received any amount of RDV and had a delivery visit, and had available head circumference measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 | Safety Outcome: Mean Newborn Head Circumference in Arm 1 | 29.9 cm |
Primary
Safety Outcome: Mean Newborn Length in Arm 1
We present the newborn mean length among the participants who had a live born infant, bounded by a 95% confidence interval (CI) calculated using the t distribution.
Time frame: Delivery
Population: Infants born to Arm 1 women, who received any amount of RDV and had a delivery visit, and had available length measurement.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 | Safety Outcome: Mean Newborn Length in Arm 1 | 44.1 cm |
Primary
Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1
We present the proportion of participants who had a live infant born with congenital anomalies at delivery, bounded by an exact 95% confidence interval (CI).
Time frame: Delivery
Population: Arm 1 women who receive any amount of RDV, had a delivery visit, and had a live-born infant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1 | 0.00 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher AE assessed as related to RDV by the CMC through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Time frame: First infusion through 4 Weeks post-last infusion and Delivery
Population: Arm 1 women who receive any amount of RDV and had follow-up through 4 weeks post-last infusion and delivery or at least one maternal grade 3 or higher adverse event assessed as related to RDV by the CMC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 1 | 0.00 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one maternal grade 3 or higher adverse event through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Time frame: First infusion through 4 Weeks post-last infusion and Delivery
Population: Arm 1 women who receive any amount of RDV and had follow-up through 4 weeks post-last infusion and delivery or at least one maternal grade 3 or higher adverse event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1 | 0.68 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term Blood and lymphatic system disorders and high level grouping term Haematology investigations (incl blood groups). The number of RDV infusions varied by participant.
Time frame: First infusion through 7 Days post-last infusion
Population: Arm 1 women who receive any amount of RDV and had follow-up through 7 days post-last infusion or a hematologic adverse event of any grade.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1 | 0.30 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term Hepatobiliary disorders and high level grouping term Hepatobiliary investigations. The number of RDV infusions varied by participant.
Time frame: First infusion through 7 Days post-last infusion
Population: Arm 1 women who receive any amount of RDV and had follow-up through 7 days post-last infusion or a hepatic adverse event of any grade.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1 | 0.04 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term Renal and urinary disorders and high level grouping term Renal and urinary tract investigations and urinalyses. The number of RDV infusions varied by participant.
Time frame: First infusion through 7 Days post-last infusion
Population: Arm 1 women who receive any amount of RDV and had follow-up through 7 days post-last infusion or a renal adverse event of any grade.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1 | 0 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1
We present the proportion of participants who had a pregnancy loss at delivery, bounded by an exact 95% confidence interval (CI).
Time frame: Delivery
Population: Arm 1 women who receive any amount of RDV and had a delivery visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1 | 0.06 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 34 Weeks in Arm 1
We present the proportion of participants who had a live preterm birth defined as \< 34 weeks, bounded by an exact 95% confidence interval (CI).
Time frame: Delivery
Population: Arm 1 women who receive any amount of RDV, had a delivery visit, and had a live-born infant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 34 Weeks in Arm 1 | 0.00 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1
We present the proportion of participants who had a live preterm birth defined as \< 37 weeks, bounded by an exact 95% confidence interval (CI).
Time frame: Delivery
Population: Arm 1 women who receive any amount of RDV, had a delivery visit, and had a live-born infant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1 | 0.25 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one maternal serious AE through 4 weeks post last infusion and delivery, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Time frame: First infusion through 4 Weeks post-last infusion and Delivery
Population: Arm 1 women who receive any amount of RDV and had follow-up through 4 weeks post-last infusion and delivery or at least one maternal serious adverse event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1 | 0.33 proportion of participants |
Primary
Safety Outcome: Proportion of Participants With Small for Gestational Age, Defined as < 10th Percentile in Arm 1
We present the proportion of participants who a live born infant who was small for gestational age defined as \< 10th percentile, bounded by an exact 95% confidence interval (CI).
Time frame: Delivery
Population: Arm 1 women who receive any amount of RDV, had a delivery visit, and had a live-born infant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Small for Gestational Age, Defined as < 10th Percentile in Arm 1 | 0.13 proportion of participants |
Secondary
PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 2
AUC calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Population: Arm 2 women who met the following minimum sampling requirements: (1) at least 3 out of 4 of the end of infusion (EOI) through 3 hours post-end-of-infusion (post-EOI) intensive PK samples AND (2) either the 5 hours post-EOI or the 7 hours post-EOI intensive PK sample AND (3) either the pre-dose or 23-hour post-EOI intensive PK sample, had at least two drug concentrations greater than the lower limit of quantification, and had an available RDV AUC measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 | PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 2 | 1302.75 h*ng/mL |
Secondary
PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 2
t1/2 calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Population: Arm 2 women who met the following minimum sampling requirements: (1) at least 3 out of 4 of the end of infusion (EOI) through 3 hours post-end-of-infusion (post-EOI) intensive PK samples AND (2) either the 5 hours post-EOI or the 7 hours post-EOI intensive PK sample AND (3) either the pre-dose or 23-hour post-EOI intensive PK sample, had at least two drug concentrations greater than the lower limit of quantification, and had an available RDV t1/2 measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 | PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 2 | 1.09 hours |
Secondary
PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 2
GS-441524 is a metabolite of remdesivir (RDV). Ctrough calculated using non-compartmental methods with linear up-log down trapezoidal rule (Phoenix WinNonlin v 8.3, Certara®). Intensive PK sampling occurred once, on the day of the 3rd, 4th, or 5th infusion.
Time frame: At 3rd, 4th, or 5th infusion. Collection timepoints included: pre-dose, end of infusion (EOI), EOI + 0.75 hours, EOI + 1.5 hours, EOI + 3 hours, EOI + 5 hours, EOI + 7 hours, EOI + 23 hours.
Population: Arm 2 women who met the following minimum sampling requirements: (1) at least 3 out of 4 of the end of infusion (EOI) through 3 hours post-end-of-infusion (post-EOI) intensive PK samples AND (2) either the 5 hours post-EOI or the 7 hours post-EOI intensive PK sample AND (3) either the pre-dose or 23-hour post-EOI intensive PK sample, had at least two drug concentrations greater than the lower limit of quantification, and had an available GS-441524 Ctrough measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 | PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 2 | 57.1 ng/mL |
Secondary
Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one grade 3 or higher AE as related to RDV by the CMC through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Time frame: First infusion through 4 Weeks post-last infusion
Population: Arm 2 women who receive any amount of RDV and had follow-up through 4 weeks post-last infusion or at least one grade 3 or higher adverse event assess as related to RDV by the CMC.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) Assessed as Related to Remdesivir (RDV) by the Clinical Management Committee (CMC) in Arm 2 | 0.04 proportion of participants |
Secondary
Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: grade 1 indicates a mild event, grade 2 indicates a moderate event, grade 3 indicates a severe event, grade 4 indicates a potentially life-threatening event, and grade 5 indicates death. We present the proportion of participants with at least one grade 3 or higher AE through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI).
Time frame: First infusion through 4 Weeks post-last infusion
Population: Arm 2 women who receive any amount of RDV and had follow-up through 4 weeks post-last infusion or at least one grade 3 or higher adverse event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) in Arm 2 | 0.54 proportion of participants |
Secondary
Safety Outcome: Proportion of Participants With Hematologic Adverse Event (AE) of Any Grade in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one hematologic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hematologic AEs were defined using the MedDRA system organ class term Blood and lymphatic system disorders and high level grouping term Haematology investigations (incl blood groups). The number of RDV infusions varied by participant.
Time frame: First infusion through 7 Days post-last infusion
Population: Arm 2 women who receive any amount of RDV and had follow-up through 7 days post-last infusion or a hematologic adverse event of any grade.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Hematologic Adverse Event (AE) of Any Grade in Arm 2 | 0.26 proportion of participants |
Secondary
Safety Outcome: Proportion of Participants With Hepatic Adverse Event (AE) of Any Grade in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one hepatic AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Hepatic AEs were defined using the MedDRA system organ class term Hepatobiliary disorders and high level grouping term Hepatobiliary investigations. The number of RDV infusions varied by participant.
Time frame: First infusion through 7 Days post-last infusion
Population: Arm 2 women who receive any amount of RDV and had follow-up through 7 days post-last infusion or a hepatic adverse event of any grade.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Hepatic Adverse Event (AE) of Any Grade in Arm 2 | 0.04 proportion of participants |
Secondary
Safety Outcome: Proportion of Participants With Renal Adverse Event (AE) of Any Grade in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one renal AE through 7 days post last infusion, bounded by an exact 95% confidence interval (CI). Renal AEs were defined using the MedDRA system organ class term Renal and urinary disorders and high level grouping term Renal and urinary tract investigations and urinalyses. The number of RDV infusions varied by participant.
Time frame: First infusion through 7 Days post-last infusion
Population: Arm 2 women who receive any amount of RDV and had follow-up through 7 days post-last infusion or a renal adverse event of any grade.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Renal Adverse Event (AE) of Any Grade in Arm 2 | 0.04 proportion of participants |
Secondary
Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 2
Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017. We present the proportion of participants with at least one serious AE through 4 weeks post last infusion, bounded by an exact 95% confidence interval (CI). The number of RDV infusions varied by participant.
Time frame: First infusion through 4 Weeks post-last infusion
Population: Arm 2 women who receive any amount of RDV and had follow-up through 4 weeks post-last infusion or at least one serious adverse event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 2 | 0.17 proportion of participants |
Other Pre-specified
PK Outcome: Ratio of Cord Blood/Maternal Plasma GS-441524 Concentrations
GS-441524 is a metabolite of remdesivir (RDV). Ratio of cord blood/maternal plasma is calculated for women in Arm 1 who received RDV within 5 days of delivery only.
Time frame: Delivery
Population: No cord blood was collected.
Other Pre-specified
PK Outcome: Ratio of Cord Blood/Maternal Plasma Remdisivir (RDV) Concentrations
Ratio of cord blood/maternal plasma is calculated for women in Arm 1 who received RDV within 5 days of delivery only.
Time frame: Delivery
Population: No cord blood was collected.