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

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ClinicalTrials.gov Identifier: NCT04582266
Recruitment Status : Not yet recruiting
First Posted : October 9, 2020
Last Update Posted : October 9, 2020
Sponsor:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

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
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.

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Study Type : Observational
Estimated Enrollment : 40 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
Estimated Study Start Date : October 15, 2020
Estimated Primary Completion Date : January 15, 2022
Estimated Study Completion Date : January 15, 2022

Group/Cohort 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.




Primary Outcome Measures :
  1. PK Outcome: Area under the plasma concentration-time curve (AUC) of RDV [ Time Frame: Through Day 5 of infusions ]
    For Arm 1 only; Calculated using non-compartmental methods

  2. PK Outcome: Half-life (t1/2) of RDV [ Time Frame: Through Day 5 of infusions ]
    For Arm 1 only; Calculated using non-compartmental methods

  3. PK Outcome: Trough concentration (Ctrough) of GS-441524 [ Time Frame: Through Day 5 of infusions ]
    For Arm 1 only; Calculated using non-compartmental methods

  4. Safety Outcome: Maternal renal adverse event (AE) of any grade [ Time Frame: 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

  5. Safety Outcome: Maternal hepatic AE of any grade [ Time Frame: 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

  6. Safety Outcome: Maternal hematologic AE of any grade [ Time Frame: 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

  7. Safety Outcome: Maternal Grade 3 or higher AE [ Time Frame: 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

  8. Safety Outcome: Serious AE [ Time Frame: 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

  9. Safety Outcome: Maternal Grade 3 or higher AE assessed as related to RDV by the Clinical Management Committee (CMC) [ Time Frame: 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

  10. Safety Outcome: Pregnancy loss [ Time Frame: Delivery ]
    For Arm 1 only

  11. Safety Outcome: Congenital anomalies [ Time Frame: Delivery ]
    For Arm 1 only

  12. Safety Outcome: Preterm birth, defined as < 37 weeks [ Time Frame: Delivery ]
    For Arm 1 only

  13. Safety Outcome: Preterm birth, defined as < 34 weeks [ Time Frame: Delivery ]
    For Arm 1 only

  14. Safety Outcome: Small for gestational age, defined as < 10th percentile [ Time Frame: Delivery ]
    For Arm 1 only

  15. Safety Outcome: Newborn birth weight [ Time Frame: Delivery ]
    For Arm 1 only

  16. Safety Outcome: Newborn length [ Time Frame: Delivery ]
    For Arm 1 only

  17. Safety Outcome: Newborn head circumference [ Time Frame: Delivery ]
    For Arm 1 only


Secondary Outcome Measures :
  1. PK Outcome: AUC of RDV [ Time Frame: Through Day 5 of infusions ]
    For Arm 2 only; Calculated using non-compartmental methods

  2. PK Outcome: t1/2 of RDV [ Time Frame: Through Day 5 of infusions ]
    For Arm 2 only; Calculated using non-compartmental methods

  3. PK Outcome: Ctrough of GS-441524 [ Time Frame: Through Day 5 of infusions ]
    For Arm 2 only; Calculated using non-compartmental methods

  4. Safety Outcome: Renal AE of any grade [ Time Frame: 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

  5. Safety Outcome: Hepatic AE of any grade [ Time Frame: 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

  6. Safety Outcome: Hematologic AE of any grade [ Time Frame: 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

  7. Safety Outcome: Grade 3 or higher AE [ Time Frame: 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

  8. Safety Outcome: Serious AE [ Time Frame: 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

  9. Safety Outcome: Grade 3 or higher AE assessed as related to RDV by the CMC [ Time Frame: 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:
  1. PK Outcome: Ratio of cord blood/maternal plasma RDV concentrations [ Time Frame: Delivery ]
    For women in Arm 1 who received RDV within 5 days of delivery only

  2. PK Outcome: Ratio of cord blood/maternal plasma GS-441524 concentrations [ Time Frame: Delivery ]
    For women in Arm 1 who received RDV within 5 days of delivery only



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
This study will be conducted among hospitalized pregnant and non-pregnant women receiving RDV infusion for treatment of COVID-19 as part of their clinical care
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, 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04582266


Contacts
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Contact: Elizabeth Greene, MPH 9195447040 ext 11124 egreene@fhi360.org
Contact: Kathleen George, MPH 9195447040 ext 11150 kgeorge@fhi360.org

Locations
Show Show 17 study locations
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Investigators
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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
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Responsible Party: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT04582266    
Other Study ID Numbers: IMPAACT 2032
DAIDS Study ID 38746 ( Other Identifier: DAIDS CRMS )
First Posted: October 9, 2020    Key Record Dates
Last Update Posted: October 9, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie results in the publication, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Beginning 3 months following publication and available throughout period of funding of the International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network by NIH.
Access Criteria:
  • With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the IMPAACT Network.
  • For what types of analyses? To achieve aims in the proposal approved by the IMPAACT Network.
  • By what mechanism will data be made available? Researchers may submit a request for access to data using the IMPAACT "Data Request" form at: https://www.impaactnetwork.org/resources/study-proposals.htm. Researchers of approved proposals will need to sign an IMPAACT Data Use Agreement before receiving the data.
URL: https://www.impaactnetwork.org/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:
COVID-19, Pregnancy