The Safety of Molnupiravir (EIDD-2801) and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID)

• ClinicalTrials.gov Identifier: NCT04405739
• Recruitment Status: Recruiting
• First Posted: May 28, 2020
• Last Update Posted: February 21, 2021
• Sponsor: Ridgeback Biotherapeutics, LP
• Information provided by (Responsible Party): Ridgeback Biotherapeutics, LP

Study Description

Brief Summary:

Designed as a multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of EIDD-2801 on SARS-CoV-2 Virus Shedding in Newly Hospitalized Adults with polymerase chain reaction (PCR)-Confirmed COVID-19.

Condition or disease	Intervention/treatment	Phase
SARS-CoV 2	Drug: EIDD-2801; Drug: Placebo (PB0)	Phase 2

Detailed Description:

Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 in adult men and women who have tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection within 144 hours of polymerase chain reaction (PCR) confirmation and are hospitalized with a diagnosis of COVID-19. Rapid enrollment and treatment will be initiated such that the first dose of EIDD-2801 or placebo will be administered as soon as possible and within 7 days of onset of symptoms.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2
• Actual Study Start Date: June 16, 2020
• Estimated Primary Completion Date: May 28, 2021
• Estimated Study Completion Date: May 28, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: EIDD-2801 twice daily (BID) for 5 days; Dose A, Dose B, Dose C, Dose D, Dose E, Dose F	Drug: EIDD-2801; Oral capsule of EIDD-2801
Placebo Comparator: placebo (PBO) twice daily (BID) for 5 days	Drug: Placebo (PB0); Oral placebo capsule

Outcome Measures

Primary Outcome Measures :

1. Number of Participants that achieve Virologic Clearance after oral administration of EIDD-2801 [ Time Frame: 28 days ]
   Achievement of undetectable SARS-CoV-2 RNA by Day 5 in nasopharyngeal (NP) swabs by quantitative reverse transcription polymerase chain reaction (qPCR) after administration with EIDD-2801
2. Number of Participants With any Serious Adverse Events(SAEs) as assessed by DAIDS [ Time Frame: 28 days ]
   Incidence of Serious Adverse Events in subjects receiving EIDD-2801
3. Number of Participants With any Adverse Events(AEs) as assessed by DAIDS [ Time Frame: 28 days ]
   Incidence of Adverse Events in subjects receiving EIDD-2801

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Has COVID-19 disease, defined by having one or more of the following new symptoms and signs (within 7 days):

   • Fevers OR
   • At least one of the following symptoms: cough, shortness of breath, respiratory rate ≥ 20, radiographic evidence of pneumonia OR
   • Anosmia OR
   • other clinical symptoms or signs of COVID-19 that are not otherwise explained by comorbidities or co-diagnoses
2. PCR+ test for SARS-CoV-2.
3. Has new signs or symptoms of COVID-19 that began ≤7 days of anticipated first dose of study drug.
4. Persons ≥18 years old.
5. Is admitted and is anticipated to remain in the hospital for ≥ 24 hours.
6. Is willing and able to comply with all study procedures including providing informed consent, collection of virology samples, and any safety tests that are not included as part of standard of care (SOC).

7. Is willing and able to take oral medications, and is anticipated to be able to take the full course of 5 days of study agent.

   Pregnancy and Contraception: Treatment with EIDD-2801 is contraindicated in women who are pregnant or nursing and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during the study and for 50 days after completion of EIDD 2801 dosing in female participants and for 100 days after completion of EIDD-2801 dosing in female partners of male participants.

8. Female participants of childbearing potential must meet the the following criteria to be enrolled:

   1. Have a negative serum pregnancy test at Screening
   2. Must agree to undergo a follow-up pregnancy test on Study Day 28.
   3. 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:

   i. 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

   ii. 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.

9. Male participants must refrain from donating sperm during the study and for 100 days after dosing of the study drug is complete.

10. 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

       • 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. Has an illness within the past 30 days that requires mechanical ventilation prior to enrollment.
2. Is anticipated to require ICU admission for mechanical ventilation within 24 hours of enrollment.
3. Requires more than 6 liters/minute of oxygen to maintain O2 saturation above 95%
4. Is not expected to survive longer than 24 hours.
5. Has a platelet count less than 100,000/µL, hemoglobin less than 10 g/dL, or has a disorder of the hematologic system including anemic disorder or other blood dyscrasia, cancer of the hematologic system, history of bone marrow transplant, or other significant hematologic disease.
6. Women who are pregnant or breastfeeding.
7. Is experiencing DAIDS AE grading scale grade 4 baseline medical conditions or laboratory abnormalities..
8. Has received an experimental vaccine for COVID-19 prior to the first dose of study drug
9. Has received hydroxychloroquine or chloroquine within 30 days of study enrollment.
10. Is participating in another clinical study that involves pharmacologic intervention or has participated in another study within 30 days of 5 half-lives of the investigational agent (observational study participation is permitted).
11. In the opinion of the investigator, has end-organ disease as a result of relevant comorbidities: chronic kidney disease (reduced glomerular filtration rate (GFR) <30 mL/min by the Modification of Diet in Renal Disease (MDRD) study equation prior to COVID-19 symptom onset), decompensated chronic liver disease or cirrhosis, decompensated congestive heart failure, active peripheral vascular disease including active diabetic ulcers, chronic pulmonary disease prior to COVID-19 symptom onset requiring bilevel positive airway pressure (BiPAP) or >2 L/min supplemental oxygen at baseline; if using ≤2 L/min supplemental oxygen at baseline, consultation with and approval of the sponsor is required prior to enrollment.
12. Has a diagnosis of cancer that is not in remission. Noninvasive cancers, such as basal and squamous cell carcinoma or history of in situ tumors are allowed at the discretion of the investigator after discussion with the sponsor.
13. Has received an organ transplantation.
14. Has received a bone marrow transplantation.
15. Has been on immunosuppressive medications within one month prior to enrollment.
16. Has any condition that would, in the opinion of the investigator, put the participant at increased risk for participation in a clinical trial.
17. Has known active hepatitis C (HCV RNA positive), active hepatitis B (hepatitis B surface antigen positive), or HIV (ELISA and confirmatory Western blotting). New screening tests not required.
18. Is currently taking nucleos(t)ide analogues for HIV or Hepatitis B, or for their prevention, within 30 days of study enrollment.
19. Is currently taking systemic corticosteroids other than replacement doses, or for treatment of COVID-19.
20. Has a Body Mass Index (BMI) >50 kg/m2.
21. Is anticipated to require surgery within 48 hours after hospital admission.
22. Is anticipated to have a nothing per mouth (NPO) order placed within 48 hours after hospital admission that is expected to last for > 24 hours.

Contacts and Locations

Contacts

Contact: Laura Szewczyk; 786-687-2495; EIDD2801@ridgebackbio.com

Locations

United States, California

Ronald Reagan UCLA Medical Center; Recruiting

Los Angeles, California, United States, 90095-8358

Contact: Chen "Anna" Zheng 310-794-0129 czheng@mednet.ucla.edu

Principal Investigator: Debika Bhattacharya, MD

United States, Illinois

Cook County Hospital; Not yet recruiting

Chicago, Illinois, United States, 60612

Contact: Mathew Itteera 312-864-4606

Advocate Christ Medical Center; Recruiting

Oak Lawn, Illinois, United States, 60453

Contact: Adam Treitman, MD 847-723-8200

Advocate Lutheran General Hospital; Recruiting

Park Ridge, Illinois, United States, 60068

Contact: Adam Treitman, MD 847-723-8200

United States, Maryland

Johns Hopkins Bayview Medical Center; Recruiting

Baltimore, Maryland, United States, 21224

Contact: Stephanie Swords sswords1@jhmi.edu

Principal Investigator: Ashwan Balagopal

John Hopkins Hospital; Recruiting

Baltimore, Maryland, United States, 21287

Contact: Stephanie Swords sswords1@jhmi.edu

Principal Investigator: Ashwin Balagopal

Suburban Hospital; Recruiting

Bethesda, Maryland, United States, 20814

Contact: Stephanie Swords sswords1@jhmi.edu

Principal Investigator: Ashwin Balagopal

Howard County General Hospital; Recruiting

Columbia, Maryland, United States, 21044

Contact: Stephanie Swords sswords1@jhmi.edu

Principal Investigator: Ashwin Balagopal

United States, North Carolina

Wake Forest Baptist Health; Recruiting

Winston-Salem, North Carolina, United States, 27157

Contact: Elizabeth Zieser-Misenheimer ezeiserm@wakehealth.com

Principal Investigator: Caryn Morse, MD

United States, Tennessee

Vanderbilt University; Recruiting

Nashville, Tennessee, United States, 37235

Contact: Todd Rice, MD

United States, Texas

Houston Methodist Hospital; Recruiting

Houston, Texas, United States, 77030

Contact: Krystin Nieto 713-441-3192

Principal Investigator: Daniela Moran, MD

Sponsors and Collaborators

Ridgeback Biotherapeutics, LP

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol. 2021 Jan;6(1):11-18. doi: 10.1038/s41564-020-00835-2. Epub 2020 Dec 3.

• Responsible Party: Ridgeback Biotherapeutics, LP
• ClinicalTrials.gov Identifier: NCT04405739
• Other Study ID Numbers: EIDD-2801-2004
• First Posted: May 28, 2020
• Last Update Posted: February 21, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No