Clinical trial NCT04582266: PK and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the US
Official title: Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the United States
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Keywords: COVID-19, Pregnancy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Gilead Sciences
First posted: 2020-10-09
Enrollment: 54
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study was conducted among hospitalized pregnant and non-pregnant women receiving RDV for treatment of COVID-19 as part of their clinical care.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 1
timeFrame: 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.
measure: PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 1
timeFrame: 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.
measure: PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 1
timeFrame: 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.
measure: Safety Outcome: Proportion of Participants With Maternal Renal Adverse Event (AE) of Any Grade in Arm 1
timeFrame: First infusion through 7 Days post-last infusion
measure: Safety Outcome: Proportion of Participants With Maternal Hepatic Adverse Event (AE) of Any Grade in Arm 1
timeFrame: First infusion through 7 Days post-last infusion
measure: Safety Outcome: Proportion of Participants With Maternal Hematologic Adverse Event (AE) of Any Grade in Arm 1
timeFrame: First infusion through 7 Days post-last infusion
measure: Safety Outcome: Proportion of Participants With Maternal Grade 3 or Higher Adverse Event (AE) in Arm 1
timeFrame: First infusion through 4 Weeks post-last infusion and Delivery
measure: Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 1
timeFrame: First infusion through 4 Weeks post-last infusion and Delivery
measure: 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
timeFrame: First infusion through 4 Weeks post-last infusion and Delivery
measure: Safety Outcome: Proportion of Participants With Pregnancy Loss in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Proportion of Participants With Congenital Anomalies in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 37 Weeks in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Proportion of Participants With Preterm Birth, Defined as < 34 Weeks in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Proportion of Participants With Small for Gestational Age, Defined as < 10th Percentile in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Mean Newborn Birth Weight in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Mean Newborn Length in Arm 1
timeFrame: Delivery
measure: Safety Outcome: Mean Newborn Head Circumference in Arm 1
timeFrame: Delivery
Secondary outcomes:
measure: PK Outcome: Geometric Mean Area Under the Plasma Concentration-time Curve (AUC) of Remdesivir (RDV) in Arm 2
timeFrame: 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.
measure: PK Outcome: Geometric Mean Half-life (t1/2) of Remdesivir (RDV) in Arm 2
timeFrame: 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.
measure: PK Outcome: Geometric Mean Trough Concentration (Ctrough) of GS-441524 in Arm 2
timeFrame: 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.
measure: Safety Outcome: Proportion of Participants With Renal Adverse Event (AE) of Any Grade in Arm 2
timeFrame: First infusion through 7 Days post-last infusion
measure: Safety Outcome: Proportion of Participants With Hepatic Adverse Event (AE) of Any Grade in Arm 2
timeFrame: First infusion through 7 Days post-last infusion
measure: Safety Outcome: Proportion of Participants With Hematologic Adverse Event (AE) of Any Grade in Arm 2
timeFrame: First infusion through 7 Days post-last infusion
measure: Safety Outcome: Proportion of Participants With Grade 3 or Higher Adverse Event (AE) in Arm 2
timeFrame: First infusion through 4 Weeks post-last infusion
measure: Safety Outcome: Proportion of Participants With Serious Adverse Event (AE) in Arm 2
timeFrame: First infusion through 4 Weeks post-last infusion
measure: 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
timeFrame: First infusion through 4 Weeks post-last infusion
Other outcomes:
measure: PK Outcome: Ratio of Cord Blood/Maternal Plasma Remdisivir (RDV) Concentrations
timeFrame: Delivery
measure: PK Outcome: Ratio of Cord Blood/Maternal Plasma GS-441524 Concentrations
timeFrame: Delivery
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA (Site #: 5112)
state: California
city: Denver
country: United States
facility: Childrens Hospital (U. Colorado, Denver) NICHD CRS (Site #: 5052)
state: Colorado
city: Miami
country: United States
facility: Pediatric Perinatal HIV Clinical Trials Unit (Site #: 5127)
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine (Site #: 5030)
state: Georgia
city: Chicago
country: United States
facility: Rush University Cook County Hospital NICHD CRS (Site #: 5083)
state: Illinois
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago (LCH) CRS (Site #: 4001)
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University NICHD CRS (Site #: 5092)
state: Maryland
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital Center (Site #: 5114)
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center (Site #: 5040)
state: New York
city: Houston
country: United States
facility: Texas Children's Hospital (Site #: 5128)
state: Texas
Study officials:
affiliation: Department of Pediatrics, Boston University Chobanian and Avedisian School of Medicine
name: Mark Mirochnick, MD
role: STUDY_CHAIR
affiliation: Pediatric Infectious Diseases, Boston Medical Center
name: Diana Clarke, PharmD
role: STUDY_CHAIR
affiliation: University of California, San Diego
name: Brookie Best, PharmD, MAS
role: STUDY_CHAIR
References: