PK and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the US

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT04582266

Collaborator

(none)

Enrollment

Locations

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to describe the pharmacokinetic (PK) properties and safety of remdesivir (GS-5734TM) (RDV) administered to pregnant and non-pregnant women with COVID-19. It is a Phase I, prospective, open label, non-randomized opportunistic PK study in pregnant and non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19. RDV will not be provided as part of the study.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Remdesivir

Detailed Description

This is a Phase I 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. RDV is not provided as part of this study; a requirement for entry is that participants receive RDV as part of their clinical care (i.e., outside of the study). A target of 20 PK evaluable pregnant women will be enrolled into Arm 1; a target of 20 PK evaluable non-pregnant women of childbearing potential will be enrolled into Arm 2. Study sites will be located in the United States.

Participants will be pregnant and non-pregnant women hospitalized for COVID-19 and will receive daily RDV infusions, typically for 5 days but in some cases for up to 10 days, as part of their clinical care. RDV will be provided and managed by the participants' treating physician and will not be provided as a part of this study. Participants will undergo intensive PK sampling.

For all women, clinical and laboratory evaluations will be abstracted from the medical record. Pregnancy, birth, and infant outcomes will be obtained from pregnant women enrolled in Arm 1. Women will be followed for safety through 4 weeks after the last infusion; Arm 1 women who are still pregnant at that time will also be followed for safety at delivery.

Study Design

Study Type:

Observational

Actual Enrollment :

54 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the United States

Actual Study Start Date :

Feb 12, 2021

Actual Primary Completion Date :

Apr 13, 2022

Actual Study Completion Date :

Apr 13, 2022

Arms and Interventions

Arm	Intervention/Treatment
Arm 1 Pregnant women hospitalized and receiving RDV for treatment of COVID-19.	Drug: Remdesivir RDV will not be provided as part of the study. Participants will be administered RDV intravenously once daily for up to 10 days per clinical care.
Arm 2 Non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19.	Drug: Remdesivir RDV will not be provided as part of the study. Participants will be administered RDV intravenously once daily for up to 10 days per clinical care.

Arm

Intervention/Treatment

Arm 1

Pregnant women hospitalized and receiving RDV for treatment of COVID-19.

Drug: Remdesivir

RDV will not be provided as part of the study. Participants will be administered RDV intravenously once daily for up to 10 days per clinical care.

Arm 2

Non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19.

Drug: Remdesivir

RDV will not be provided as part of the study. Participants will be administered RDV intravenously once daily for up to 10 days per clinical care.

Outcome Measures

Primary Outcome Measures

PK Outcome: Area under the plasma concentration-time curve (AUC) of RDV [Through Day 5 of infusions]
For Arm 1 only; Calculated using non-compartmental methods
PK Outcome: Half-life (t1/2) of RDV [Through Day 5 of infusions]
For Arm 1 only; Calculated using non-compartmental methods
PK Outcome: Trough concentration (Ctrough) of GS-441524 [Through Day 5 of infusions]
For Arm 1 only; Calculated using non-compartmental methods
Safety Outcome: Maternal renal adverse event (AE) of any grade [Through 7 Days post-last infusion]
For Arm 1 only; 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
Safety Outcome: Maternal hepatic AE of any grade [Through 7 Days post-last infusion]
For Arm 1 only; 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
Safety Outcome: Maternal hematologic AE of any grade [Through 7 Days post-last infusion]
For Arm 1 only; 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
Safety Outcome: Maternal Grade 3 or higher AE [Through 4 Weeks post-last infusion and Delivery]
For Arm 1 only; 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
Safety Outcome: Serious AE [Through 4 Weeks post-last infusion and Delivery]
For Arm 1 only; 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
Safety Outcome: Maternal Grade 3 or higher AE assessed as related to RDV by the Clinical Management Committee (CMC) [Through 4 Weeks post-last infusion and Delivery]
For Arm 1 only; 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
Safety Outcome: Pregnancy loss [Delivery]
For Arm 1 only
Safety Outcome: Congenital anomalies [Delivery]
For Arm 1 only
Safety Outcome: Preterm birth, defined as < 37 weeks [Delivery]
For Arm 1 only
Safety Outcome: Preterm birth, defined as < 34 weeks [Delivery]
For Arm 1 only
Safety Outcome: Small for gestational age, defined as < 10th percentile [Delivery]
For Arm 1 only
Safety Outcome: Newborn birth weight [Delivery]
For Arm 1 only
Safety Outcome: Newborn length [Delivery]
For Arm 1 only
Safety Outcome: Newborn head circumference [Delivery]
For Arm 1 only

Secondary Outcome Measures

PK Outcome: AUC of RDV [Through Day 5 of infusions]
For Arm 2 only; Calculated using non-compartmental methods
PK Outcome: t1/2 of RDV [Through Day 5 of infusions]
For Arm 2 only; Calculated using non-compartmental methods
PK Outcome: Ctrough of GS-441524 [Through Day 5 of infusions]
For Arm 2 only; Calculated using non-compartmental methods
Safety Outcome: Renal AE of any grade [Through 7 Days post-last infusion]
For Arm 2 only; 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
Safety Outcome: Hepatic AE of any grade [Through 7 Days post-last infusion]
For Arm 2 only; 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
Safety Outcome: Hematologic AE of any grade [Through 7 Days post-last infusion]
For Arm 2 only; 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
Safety Outcome: Grade 3 or higher AE [Through 4 Weeks post-last infusion]
For Arm 2 only; 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
Safety Outcome: Serious AE [Through 4 Weeks post-last infusion]
For Arm 2 only; 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
Safety Outcome: Grade 3 or higher AE assessed as related to RDV by the CMC [Through 4 Weeks post-last infusion]
For Arm 2 only; 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

Other Outcome Measures

PK Outcome: Ratio of cord blood/maternal plasma RDV concentrations [Delivery]
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]
For women in Arm 1 who received RDV within 5 days of delivery only

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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, not within 6 weeks postpartum, based on participant report, medical records, 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Usc La Nichd Crs	Los Angeles	California	United States	90033-1075
2	USC/Los Angeles County Medical Center NICHD CRS (5048)	Los Angeles	California	United States	90089
3	David Geffen School of Medicine at UCLA (CRS 5112)	Los Angeles	California	United States	90095
4	University California, San Diego (CRS 4601)	San Diego	California	United States	92103
5	Childrens Hospital (U. Colorado, Denver) NICHD CRS (5052)	Denver	Colorado	United States	80218-1088
6	University of Florida (5051)	Jacksonville	Florida	United States	32209
7	Univ of Miami Pediatric/Perinatal HIV/AIDS (4201)	Miami	Florida	United States	33136
8	Emory University School of Medicine (CRS 5030)	Atlanta	Georgia	United States	30308
9	Ann & Robert H Lurie Children's Hospital of Chicago (4001)	Chicago	Illinois	United States	60611
10	Rush University Cook County Hospital NICHD CRS (5083)	Chicago	Illinois	United States	60612
11	Lurie Children's Hospital of Chicago (LCH) CRS	Chicago	Illinois	United States	60614
12	Johns Hopkins University NICHD CRS (5092)	Baltimore	Maryland	United States	21287
13	Boston Medical Center Ped. HIV Program NICHD CRS (5011)	Boston	Massachusetts	United States	02118
14	Bronx-Lebanon Hospital Center (CRS 5114)	Bronx	New York	United States	10457
15	Stony Brook University Medical Center (CRS 5040)	Stony Brook	New York	United States	11794
16	St. Jude Childrens Research Hosp, Memphis (6501)	Memphis	Tennessee	United States	38105
17	Texas Children's Hospital (Site 5128)	Houston	Texas	United States	77030
18	University of Puerto Rico Pediatric HIV/AIDS CRS (6601)	San Juan		Puerto Rico	00936-5067

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair: Mark Mirochnick, MD, Department of Pediatrics, Boston University
Study Chair: Diana Clarke, PharmD, Pediatric Infectious Diseases, Boston Medical Center
Study Chair: Brookie Best, PharmD, MAS, University of California, San Diego

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT04582266

Other Study ID Numbers:

IMPAACT 2032
DAIDS Study ID 38746

First Posted:

Oct 9, 2020

Last Update Posted:

Aug 16, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)

COVID-19, Pregnancy

Additional relevant MeSH terms:

COVID-19

Remdesivir

Study Results

No Results Posted as of Aug 16, 2022