SARS-CoV 2Phase 2NCT04405739
The Safety of Molnupiravir (EIDD-2801) and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID)
A Phase 2 study testing EIDD-2801 in people with SARS-CoV 2, run by Ridgeback Biotherapeutics, LP at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SARS-CoV 2
- What is being tested?
- EIDD-2801
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 11 sitesUnited States
- Study dates
- 16 Jun 2020to 21 Feb 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- PCR+ test for SARS-CoV-2.
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- Has new signs or symptoms of COVID-19 that began ≤7 days of anticipated first dose of study drug.
- Persons ≥18 years old.
- at the time of first dose.
- 5. ≥18 years old.
- 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 drug.
- Pregnancy and Contraception: In nonclinical developmental and reproductive toxicity studies, developmental toxicity including malformation was observed in fetuses from pregnant animals dosed with EIDD-2801 (MK 4482). Therefore, 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 4 days after completion of EIDD 2801 dosing in female participants and for 4 days after completion of EIDD-2801 dosing in female partners of male participants.
- 8. A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP) OR
- Is 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 be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 2 during the intervention period and for at least 4 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
- A WOCBP must have a negative highly sensitive pregnancy test (serum test is required) within 24 hours before the first dose of study intervention.
- Additional requirements for pregnancy testing during and after study intervention are located in Section 4.4.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Given the elevated risk of venous thrombotic events in patients hospitalized with COVID 19 (Benson et al 2020; Spratt et al 2020), estrogen-containing contraceptives must not be started to fulfill the contraceptive requirement of this study at any time during participant's hospitalization. If contraceptives are interrupted as standard of care management of COVID-19 patients and resumed at a later time point, such as at hospital discharge, then abstinence must be practiced for the defined period of back-up contraception per the contraceptive product labeling. After this period, contraceptive use must adhere to Appendix 2.
- 9. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 4 days after the last dose of study intervention:
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
- Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause [Appendix 2]) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Who cannot join
- Is anticipated to require ICU admission for mechanical ventilation within 24 hours of enrollment.
- Requires more than 6 liters/minute of oxygen to maintain O2 saturation above 95%
- Is not expected to survive longer than 24 hours.
- Has a platelet count less than 100,000/µL, hemoglobin less than 9 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.
- Women who are pregnant or breastfeeding.
- Is experiencing DAIDS AE grading scale grade 4 baseline medical conditions or laboratory abnormalities..
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- Has received a vaccine for COVID-19 prior to enrollment, or plans to receive a vaccine for COVID-19 before the end-of-study visit.
- Has received an experimental antiviral treatment for COVID-19 prior to enrollment.
- Has received convalescent plasma or other monoclonal antibodies prior to enrollment..
- 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).
- 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 >4 L/min supplemental oxygen at baseline; if using ≤4 L/min supplemental oxygen at baseline, consultation with and approval of the sponsor is required prior to enrollment.
- 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.
- Has received an organ transplantation.
- Has received a bone marrow transplantation.
- Has been on immunosuppressive medications within one month prior to enrollment.
- Has any condition that would, in the opinion of the investigator, put the participant at increased risk for participation in a clinical trial.
- 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.
- Is currently taking nucleos(t)ide analogues for HIV or Hepatitis B, or for their prevention, within 30 days of study enrollment.
- Is currently taking systemic corticosteroids other than replacement doses, or for treatment of COVID-19.
- Has a Body Mass Index (BMI) >50 kg/m2.
- Is anticipated to require surgery within 48 hours after hospital admission.
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
John Hopkins Hospital
Baltimore, Maryland, 21287
Cook County Hospital
Chicago, Illinois, 60612
Howard County General Hospital
Columbia, Maryland, 21044
Houston Methodist Hospital
Houston, Texas, 77030
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095-8358
Vanderbilt University
Nashville, Tennessee, 37235
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068
Ochsner LSU Health Shreveport Academic Medical Center
Shreveport, Louisiana, 71101
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
Official title: The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2
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.
Read the detailed description
Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 (also known as MK 4482) in adult men and women who have tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection by polymerase chain reaction (PCR) test within 6 days (144 hours) prior to randomization 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.
- Conditions
- SARS-CoV 2
- Being tested
- EIDD-2801, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EIDD-2801Drug
Also called molnupiravir, MK-4482
Oral capsule of EIDD-2801
PlaceboDrug
Also called PBO
Oral placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| EIDD-2801 twice daily (BID) for 5 days | Experimental | EIDD-2801 orally twice daily (BID) for 5 days at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F Receives: Drug: EIDD-2801 |
| placebo (PBO) twice daily (BID) for 5 days | Placebo comparator | Placebo (PBO) orally twice daily (BID) for 5 days matched for size and appearance to active IP Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Achieve Virologic Clearance After Oral Administration of EIDD-2801
Achievement of undetectable (below the limit of detection of the assay) SARS-CoV-2 RNA by day 5 in NP swabs by quantitative Polymerase Chain Reaction (qPCR) in the Efficacy Analysis Set (EAS). The Efficacy Analysis Set consisted of all participants treated with at least on dose of study drug and with at least 1 post baseline assessment of SARS-CoV-2 RNA in NP swabs by qPCR
Measured: 28 days
Number of Participants With Any Serious Adverse Events(SAEs) as Assessed by DAIDS
Incidence of Serious Adverse Events in subjects receiving EIDD-2801 as assessed by DAIDS in the Safety Population, defined as all participants treated with at least one dose of study drug.
Measured: 28 days
Number of Participants With Any Adverse Events(AEs) as Assessed by DAIDS
Incidence of Adverse Events in subjects receiving EIDD-2801 as assessed by DAIDS
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2020
- Study start16 Jun 2020
- Primary completion21 Feb 2022
- Study completion21 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ridgeback Biotherapeutics, LP
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Ashwin Balagopal, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04405739
- Sponsor's protocol ID
- EIDD-2801-2004
- Status last verified
- Mar 2023
- First submitted
- 26 May 2020
- Last updated
- 23 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 33273742
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2
- ClinicalTrials.gov ID
- NCT04405739
- Acronym / sponsor ID
- EIDD-2801-2004
- Conditions
- SARS-CoV 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Ridgeback Biotherapeutics, LPIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 16 Jun 2020 (actual)
- Primary completion
- 21 Feb 2022 (actual)
- Study completion
- 21 Feb 2022 (actual)
- First posted
- 28 May 2020 (actual)
- Results
- Posted 23 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 (also known as MK 4482) in adult men and women who have tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection by polymerase chain reaction (PCR) test within 6 days (144 hours) prior to randomization 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EIDD-2801 twice daily (BID) for 5 days | Experimental | Drug: EIDD-2801EIDD-2801 orally twice daily (BID) for 5 days at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F |
| placebo (PBO) twice daily (BID) for 5 days | Placebo comparator | Drug: PlaceboPlacebo (PBO) orally twice daily (BID) for 5 days matched for size and appearance to active IP |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Has COVID-19 disease, defined by having one or more of the following new symptoms and signs (within 7 days):
- PCR+ test for SARS-CoV-2.
- Has new signs or symptoms of COVID-19 that began ≤7 days of anticipated first dose of study drug.
- Persons ≥18 years old.
- at the time of first dose.
Key exclusion criteria (22 listed)
- Is anticipated to require ICU admission for mechanical ventilation within 24 hours of enrollment.
- Requires more than 6 liters/minute of oxygen to maintain O2 saturation above 95%
- Is not expected to survive longer than 24 hours.
- Has a platelet count less than 100,000/µL, hemoglobin less than 9 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.
- Women who are pregnant or breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EIDD-2801Also: molnupiravir, MK-4482Oral capsule of EIDD-2801 | Drug | EIDD-2801 twice daily (BID) for 5 days |
| PlaceboAlso: PBOOral placebo capsule | Drug | placebo (PBO) twice daily (BID) for 5 days |
Primary outcome
Number of Participants That Achieve Virologic Clearance After Oral Administration of EIDD-2801
Time frame: 28 days
Achievement of undetectable (below the limit of detection of the assay) SARS-CoV-2 RNA by day 5 in NP swabs by quantitative Polymerase Chain Reaction (qPCR) in the Efficacy Analysis Set (EAS). The Efficacy Analysis Set consisted of all participants treated with at least on dose of study drug and with at least 1 post baseline assessment of SARS-CoV-2 RNA in NP swabs by qPCR
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 as assessed by DAIDS in the Safety Population, defined as all participants treated with at least one dose of study drug.
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 as assessed by DAIDS
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33273742Cox 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashwin Balagopal, MD principal investigator
Johns Hopkins University
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EIDD-2801 in people with SARS-CoV 2, run by Ridgeback Biotherapeutics, LP at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants That Achieve Virologic Clearance After Oral Administration of EIDD-2801 (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04405739, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2023.