Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Safety, Tolerability and Efficacy of Molnupiravir (EIDD-2801) to Eliminate Infectious Virus Detection in Persons With COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04405570
Recruitment Status : Completed
First Posted : May 28, 2020
Last Update Posted : February 23, 2021
Sponsor:
Information provided by (Responsible Party):
Ridgeback Biotherapeutics, LP

Tracking Information
First Submitted Date  ICMJE May 26, 2020
First Posted Date  ICMJE May 28, 2020
Last Update Posted Date February 23, 2021
Actual Study Start Date  ICMJE June 16, 2020
Actual Primary Completion Date February 21, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2020)
  • Virologic Efficacy [ Time Frame: 28 days ]
    The distribution of days until first non-detectable SARS-CoV-2 in nasopharyngeal (NP) swabs will be estimated for each randomized arm (drug versus placebo), using Kaplan-Meier methods with a corresponding stratified log-rank test (to account for the "early" versus "late" time from symptom onset randomization strata). Non detectable defined as "a viral load below the limit of quantification
  • Number of Participants with any Adverse Events (AEs) as Assessed by Kaplan Meier Approach [ Time Frame: 28 days ]
    Measure the safety and tolerability of EIDD-2801 by estimating in the randomization arm the probability of 1) any adverse events (AEs) leading to early discontinuation of blinded treatment (active or placebo), 2) study drug-related discontinuation of treatment, 3) new grade 3 or higher AE (not already present at baseline), and 4) study drug-related new grade 3 or higher AE. The cumulative probability of each safety and each tolerability endpoint (4 endpoints) by using the Kaplan-Meier approach and stratified log-rank test.
Original Primary Outcome Measures  ICMJE
 (submitted: May 26, 2020)
  • Virologic Efficacy [ Time Frame: 28 days ]
    The distribution of days until first non-detectable SARS-CoV-2 in nasopharyngeal (NP) swabs will be estimated for each randomized arm (drug versus placebo), using Kaplan-Meier methods with a corresponding stratified log-rank test (to account for the "early" versus "late" time from symptom onset randomization strata)
  • Number of Participants with any Adverse Events (AEs) as Assessed by Kaplan Meier Approach [ Time Frame: 28 days ]
    Measure the safety and tolerability of EIDD-2801 by estimating in the randomization arm the probability of 1) any adverse events (AEs) leading to early discontinuation of blinded treatment (active or placebo), 2) study drug-related discontinuation of treatment, 3) new grade 3 or higher AE (not already present at baseline), and 4) study drug-related new grade 3 or higher AE. The cumulative probability of each safety and each tolerability endpoint (4 endpoints) by using the Kaplan-Meier approach and stratified log-rank test.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2020)
Number of Participants With any Adverse Events (AEs), Grade 2 or higher as Assessed by Kaplan Meier Approach [ Time Frame: 28 days ]
Measure the safety and tolerability of EIDD-2801 by estimating the occurrence of Grade 2 or higher AE and drug related AEs by using the Kaplan-Meier approach and stratified log-rank test.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety, Tolerability and Efficacy of Molnupiravir (EIDD-2801) to Eliminate Infectious Virus Detection in Persons With COVID-19
Official Title  ICMJE A Phase IIa Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19
Brief Summary This is a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 versus placebo as measured by infectious virus detection in symptomatic adult outpatients with COVID-19
Detailed Description

This is a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 versus placebo as measured by infectious virus detection in symptomatic adult outpatients with COVID-19. The study is a multicenter trial that will be conducted in the United States.

In this study up to approximately 108 participants will be randomized to receive EIDD-2801 or Placebo orally twice a day (BID) for 5 days. The study may enroll up to 5 parts with subsequent doses that may be higher or lower than doses studied in previous cohorts, and will be doses that have been studied for safety in a Phase 1 study. Doses will be chosen based on emerging virology and safety data from this and ongoing studies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE SARS-CoV 2
Intervention  ICMJE
  • Drug: EIDD-2801
    Oral capsule of EIDD-2801
  • Drug: Placebo (PBO)
    Placebo oral capsule
Study Arms  ICMJE
  • Experimental: EIDD-2801 twice daily (BID) for 5 days
    Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, Dose H, Dose, I
    Intervention: Drug: EIDD-2801
  • Placebo Comparator: placebo (PBO) twice daily (BID for five days
    Intervention: Drug: Placebo (PBO)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 7, 2020)
204
Original Estimated Enrollment  ICMJE
 (submitted: May 26, 2020)
44
Actual Study Completion Date  ICMJE February 21, 2021
Actual Primary Completion Date February 21, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Able to provide informed consent prior to initiation of any study procedures.
  2. ≥18 years of age at Screening.
  3. Study treatment is expected to begin within ≤168 hours from first symptom onset.
  4. Ability to swallow pills.
  5. Documentation of confirmed active SARS-CoV-2 infection, as determined by a molecular test conducted at any US clinic or laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent from an NP swab collected ≤96 hours prior to study entry.
  6. Experiencing at least one of the following SARS-CoV-2 infection symptoms: fever (can be subjective including feeling feverish or having chills) OR signs/symptoms of respiratory illness (including but not limited to upper respiratory congestion, loss of sense of smell or taste, sore throat OR lower respiratory illness - cough, shortness of breath).
  7. Agrees to not participate in another interventional clinical trial for the treatment of SARS-CoV-2 during the study period (28 days) unless hospitalized.
  8. Agrees to not obtain investigational medications outside of the EIDD-2801 study.
  9. Agrees to the sampling detailed in the schedule of evaluations (SOE) and to comply with study requirements including contraception requirements.
  10. Female participants of childbearing potential must meet the following criteria to be enrolled:

    i. Have a negative pregnancy test at Day 1, prior to randomization.

    ii. Must agree to undergo a follow-up pregnancy test on Study Day 28.

    iii. Must agree to use at least 2 forms of contraception during the study and for at least 50 days after dosing of the study drug is complete, as discussed with and approved by the investigator.

    OR Must have an azoospermic partner (vasectomized or due to a to medical cause). Note: azoospermic partner is acceptable provided that the partner is the sole sexual partner of the woman of childbearing potential and the absence of sperm has been confirmed.

    Note that female not of childbearing potential is defined as either:

    1. Surgically sterile: females who are permanently sterile via hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy by reported medical history and/or medical records. Surgical sterilization to have occurred a minimum of 6 weeks, or at the Investigator's discretion, prior to Screening. OR
    2. Postmenopausal: Females at least 60 years of age with amenorrhea for ≥12 months (by history) or 45 years of age with amenorrhea for 12 months without an alternative medical reason with confirmatory follicle stimulating hormone levels of ≥40 mIU/mL. The amenorrhea should not be induced by a medical condition such as anorexia nervosa, hypothyroid disease or polycystic ovarian disease, or by extreme exercise. It should not be due to concomitant medications that may have induced the amenorrhea such as oral contraceptives, hormones, gonadotropin releasing hormones, anti-estrogens, or selective estrogen receptor modulators.
  11. Male participants must refrain from donating sperm during the study and for 100 days after dosing of the study drug is complete.
  12. Male participants with female partners must have either

    1. Surgical sterilization (vasectomy ≥1 month before screening) OR
    2. Female partner must be of not be of childbearing potential OR
    3. Agree to use 2 forms of contraception during the study and for 100 days after dosing of the study drug is complete, as discussed with and approved by the investigator

Exclusion Criteria:

  1. Need for hospitalization or immediate medical attention in the clinical opinion of the study investigator.
  2. Hemoglobin <10 g/dL in men and <9 g/dL in women.
  3. Platelet count <125,000/L.
  4. Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73m2
  5. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥3x upper limit normal (ULN).
  6. History of or current hospitalization for COVID-19. Note: Individuals hospitalized and then discharged, even if only hospitalized for 1 day, are excluded.
  7. History of significant kidney disease in the opinion of the site investigator. Note: If the individual responds "yes" but can provide a creatinine clearance value ≥60 mL/min by Cockcroft Gault equation within 1 year prior to study entry, the individual may participate.
  8. History of significant liver disease in the opinion of the site investigator or active Hepatitis B or active Hepatitis C. Human immunodeficiency virus (HIV) that is advanced (CD4<200/mm3) and/or on treatment with nucleoside analogues.
  9. History of known blood dyscrasia
  10. Use of therapeutic interventions with possible anti-SARS-CoV-2 activity within 30 days prior to study entry, e.g., remdesivir, lopinavir/ritonavir fixed dose combination, ribavirin, chloroquine, hydroxychloroquine, convalescent plasma, or participation in a clinical trial involving any of these drugs whether for treatment or prophylaxis.
  11. Receipt of a SARS-CoV-2 vaccination prior to study entry.
  12. Known allergy/sensitivity or any hypersensitivity to components of EIDD-2801, or its formulation.
  13. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  14. History of recent hemorrhagic cerebrovascular accident (CVA) or major bleed.
  15. Presence of a condition, that in the opinion of the investigator, would place the subject at increased risk from study participation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04405570
Other Study ID Numbers  ICMJE EIDD-2801-2003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ridgeback Biotherapeutics, LP
Study Sponsor  ICMJE Ridgeback Biotherapeutics, LP
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ridgeback Biotherapeutics, LP
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP