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

NCT04405570 | Completed Phase 2 Results FDA Drug

• 1 other identifier: EIDD-2801-2003
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 10

Brief Summary

This was a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 (molnupiravir) versus placebo as measured by SARS-CoV-2 viral RNA detection in symptomatic adult outpatients with COVID-19.

Conditions

SARS-CoV-2 Infection, COVID-19

Outcome Measures

Primary Outcomes (3)

• Number of Participants Until First Non-detectable SARS-CoV-2 in Nasopharyngeal (NP) Swabs

  The number of participants 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 log-rank test. Non detectable defined as "a viral load below the limit of quantification

  28 days

• Time to Clearance of SARS-CoV-2 in Nasopharyngeal Swabs

  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 log-rank test. Non detectable defined as "a viral load below the limit of quantification

  28 days

• Number of Participants With Adverse Events (AEs) Grade 3 or Higher or Leading to Discontinuation of Study Treatment

  1\) any AEs leading to early discontinuation of blinded treatment (active or placebo), 2) study drug-related discontinuation of treatment, 3) new grade 3 or higher AEs (not already present at baseline), and 4) study drug-related new grade 3 or higher AEs.

  28 days

Secondary Outcomes (1)

• Number of Participants With Any Adverse Events (AEs), Grade 2 or Higher

  28 days

Study Arms (4)

Molnupiravir 200 mg

EXPERIMENTAL

Molnupiravir 200 mg, twice daily (BID) for 5 days

Drug: Molnupiravir 200 mg

Molnupiravir 400 mg

EXPERIMENTAL

Molnupiravir 400 mg, twice daily (BID) for 5 days

Drug: Molnupiravir 400 mg

Molnupiravir 800 mg

EXPERIMENTAL

Molnupiravir 800 mg, twice daily (BID) for 5 days

Drug: Molnupiravir 800 mg

Placebo (PBO) twice daily (BID) for 5 days

PLACEBO COMPARATOR

Drug: Placebo (PBO)

Interventions

Molnupiravir 200 mg DRUG

Oral capsule of molnupiravir

Molnupiravir 200 mg

Molnupiravir 400 mg DRUG

Oral capsule of molnupiravir

Molnupiravir 400 mg

Molnupiravir 800 mg DRUG

Oral capsule of molnupiravir

Molnupiravir 800 mg

Placebo (PBO) DRUG

placebo oral capsule

Placebo (PBO) twice daily (BID) for 5 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent prior to initiation of any study procedures.
• ≥18 years of age at Screening.
• Study treatment is expected to begin within ≤168 hours from first symptom onset.
• Ability to swallow pills.
• Documentation of confirmed active SARS-CoV-2 infection, as determined by a molecular or non-molecular ("rapid") test conducted at any clinic or laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent from a sample collected ≤96 hours prior to study entry.
• Was experiencing at least one of the following SARS-CoV-2 infection symptoms at the time of enrollment: fever (could 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).
• Agreed to not participate in another interventional clinical trial for the treatment of SARS-CoV-2 during the study period (28 days) unless hospitalized.
• Agreed to not obtain investigational medications outside of the molnupiravir study.
• Agreed to the sampling detailed in the schedule of evaluations and to comply with study requirements including contraception requirements.
• A female participant was eligible to participate if she was not pregnant or breastfeeding and at least one of the following conditions applied:
• Was not a woman of childbearing potential (WOCBP) OR
• Was a WOCBP and using a contraceptive method that is highly effective (a low user dependency method OR a user-dependent method in combination with a barrier method), or was abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 2 of the study protocol during the intervention period and for at least 50 days after the last dose of study intervention. The investigator evaluated the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have had a negative highly sensitive pregnancy test (serum or urine) within 24 hours before the first dose of study intervention.
• Additional requirements for pregnancy testing during and after study intervention were provided in the study protocol.
• Contraceptive use by women was to be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• Need for hospitalization or immediate medical attention in the clinical opinion of the study investigator.
• Hemoglobin \<10 g/dL in men and \<9 g/dL in women.
• Platelet count \<100,000/ µL or received a platelet transfusion within 5 days prior to enrollment.
• Was on dialysis or has an estimated glomerular filtration rate \<30 mL/min/1.73 m\^2
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>3x upper limit normal (ULN).
• History of or current hospitalization for COVID-19. Note: Individuals hospitalized and then discharged, even if only hospitalized for 1 day, were excluded.
• History of kidney disease as evidenced by estimated creatinine clearance value \<30 mL/min.
• 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/mm\^3) and/or on treatment with nucleos(t)ide analogues.
• 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, and convalescent plasma), or participation in a clinical trial involving any of these drugs whether for treatment or prophylaxis.
• Receipt of a SARS-CoV-2 vaccination prior to study entry.
• Known allergy/sensitivity or any hypersensitivity to components of molnupiravir, or its formulation.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• History of recent (within the past 3 months) hemorrhagic cerebrovascular accident) or major bleed.
• Presence of a condition, that in the opinion of the investigator, would place the subject at increased risk from study participation.

Sponsors & Collaborators

• Ridgeback Biotherapeutics, LP: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Valley Clinical Trials, Inc.

Northridge, California, 91325, United States

Location

FOMAT Medical Research

Oxnard, California, 93030, United States

Location

Southern California Emergency Medicine

Yucaipa, California, 92399, United States

Location

Indago Research and Health Center, Inc.

Hialeah, Florida, 33012, United States

Location

NOLA Research Works, LLC

New Orleans, Louisiana, 70115, United States

Location

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Care United Research, LLC

Forney, Texas, 75126, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (4)

• Mollan KR, Eron JJ, Krajewski TJ, Painter W, Duke ER, Morse CG, Goecker EA, Premkumar L, Wolfe CR, Szewczyk LJ, Alabanza PL, Loftis AJ, Degli-Angeli EJ, Brown AJ, Dragavon JA, Won JJ, Keys J, Hudgens MG, Fang L, Wohl DA, Cohen MS, Baric RS, Coombs RW, Sheahan TP, Fischer WA. Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates. Clin Infect Dis. 2022 Aug 24;75(1):e1028-e1036. doi: 10.1093/cid/ciab968.

  PMID: 35022711 DERIVED

• Fischer W, Eron JJ, Holman W, Cohen MS, Fang L, Szewczyk LJ, Sheahan TP, Baric R, Mollan KR, Wolfe CR, Duke ER, Azizad MM, Borroto-Esoda K, Wohl DA, Loftis AJ, Alabanza P, Lipansky F, Painter WP. Molnupiravir, an Oral Antiviral Treatment for COVID-19. medRxiv [Preprint]. 2021 Jun 17:2021.06.17.21258639. doi: 10.1101/2021.06.17.21258639.

  PMID: 34159342 DERIVED

• Mollan KR, Eron JJ, Krajewski TJ, Painter W, Duke ER, Morse CG, Goecker EA, Premkumar L, Wolfe CR, Szewczyk LJ, Alabanza PL, Loftis AJ, Degli-Angeli EJ, Brown AJ, Dragavon JA, Won JJ, Keys J, Hudgens MG, Fang L, Wohl DA, Cohen MS, Baric RS, Coombs RW, Sheahan TP, Fischer WA 2nd. Infectious SARS-CoV-2 Virus in Symptomatic COVID-19 Outpatients: Host, Disease, and Viral Correlates. medRxiv [Preprint]. 2021 Jun 25:2021.05.28.21258011. doi: 10.1101/2021.05.28.21258011.

  PMID: 34100024 DERIVED

• 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.

  PMID: 33273742 DERIVED

Related Links

• Benson et al, 2020. Society of Family Planning interim clinical recommendations

MeSH Terms

Conditions

COVID-19

Interventions

molnupiravir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Wendy Painter
• Organization: Ridgeback Biotherapeutics

EIDD2801@ridgebackbio.com

786-687-2495

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2020
• First Posted: May 28, 2020
• Study Start: June 19, 2020
• Primary Completion: February 21, 2021
• Study Completion: February 21, 2021
• Last Updated: February 16, 2022
• Results First Posted: February 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)