ensitrelvir in patients with SARS-CoV-2 infection; a randomized, open-label, molnupiravir-controlled study

JRCT ID: jRCTs071230014

Registered date:16/05/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: COVID-19
• Date of first enrollment: 02/06/2023
• Target sample size: 150
• Study type: Interventional

Intervention(s)

Patients will be randomly allocated to ensitrelvir or molnupiravir groups in a 1:1 ratio.

-Ensitrelvir group: take ensitrelvir fumaric acid (Xocova tablets 125 mg) once a day for 5 days on DAY 1 to 5
DAY1: 375mg (125mg x 3 tablets)
DAY2-5: 125mg (125mg x 1 tablet)

-Molnupiravir group: take molnupiravir 800mg (Lagevrio Capsules 200mg) twice a day for 5 days on DAY1-5

Outcome(s)

• Primary Outcome: Change from baseline on Day 4 in the amount of SARS-CoV-2 viral RNA.

Secondary Outcome

1)SARS-CoV-2 viral RNA levels at each time point
2) Change from baseline in SARS-CoV-2 viral RNA levels at each time point
3) Viral titer of SARS-CoV-2 at each time point
4) Change from baseline in SARS-CoV-2 viral titers at each time point
5) Viral titer positive rate of SARS-CoV-2 at each time point

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all the following criteria will be eligible for this study.
1)Patients who can voluntarily give written consent to participate in the study
2)Patients aged 18 or older at the time of informed consent
3)Patients who are considered to require administration of the study drug, such as having risk factors for severe disease
4)Patients who are confirmed positive for SARS-CoV-2 by any of the following tests by 72 hours before randomization
-Nucleic acid detection test using nasopharyngeal swab, nasal swab, or saliva
-Antigen test (quantitative) using nasopharyngeal swab, nasal swab, or saliva
-Antigen test using nasopharyngeal swab or nasal swab, or saliva (qualitative)
5)Patients with less than 72 hours from the onset of COVID-19* to randomization
*: at least 1 of 14 symptoms of COVID-19 (low energy [tiredness], muscle or body pain, headache, chills/sweating, feeling hot, or feverish, runny or stuffy nose, sore throat, cough, shortness of breath [dyspnea], nausea, vomiting, diarrhea, dysgeusia, dysosmia)
6)Patients who have a fever of 37 degrees Celsius or higher (axillary temperature) at the time screening
7)Patients who have at least 1 moderate symptom (COVID-19 symptom score: 2) among 5 COVID-19 symptoms (runny or stuffy nose, sore throat, cough, feeling hot or feverish, low energy [tiredness]) at the time of screening (excluding symptoms that existed before the onset of COVID-19). Alternatively, patients with 1 or more existing symptoms (symptoms that existed before the onset of COVID-19) that the patient judged to be moderate (COVID-19 symptom score: 2) or higher and are worsened by COVID-19 at the time of screening.
8)The following male and female
male who agrees to abide by the following during study drug administration and for 14 days after the final dose:
- Refrain from sperm donation.
In addition, you agree to any of the following.
- Do not engage in sexual intercourse with a different sex and continue to do so
or
- Follow contraceptive methods detailed below
1. Use a male condom when having intercourse with a fertile woman who is not currently pregnant. In addition, because male condoms can break or leak, the female partner should be advised of the benefits of using highly effective contraceptive methods.
2. Use male condoms in any activity that could expose another person to semen.

female who are not pregnant or breastfeeding and have any of the following conditions:
- Not a woman of childbearing potential
or
- If all the following apply
1. Female of childbearing potential who use a highly effective method of contraception that is user-independent and has an annual failure rate of less than 1% for the duration of study drug administration and for 14 days after the final dose. In addition, agree not to donate eggs (eggs, oocytes) for the purpose of reproduction during the research period.
2. Females of childbearing potential must have a sensitive pregnancy test (urine or serum test) within 24 hours prior to the first dose of study drug and the result must be negative
3. Negative urine pregnancy test not confirmed (e.g., result is equivocal), positive serum pregnancy test ruled out
To reduce the risk of enrolling female whose early pregnancy has not been detected, the investigator will check the medical history, menstrual history, and recent sexual activity, and will exclude those who determine that there is a possibility of pregnancy.

Exclude criteria

Patients who meet any of the following criteria are excluded from this study.
1)Patients with awake percutaneous oxygen saturation (SpO2) of 93% or less (room air)
2)Patients who require oxygen administration for treating SARS-CoV-2 infection
3)Patients who requiring a mechanical ventilation.
4)Patients whom the investigator (sub-investigator) strongly suspected to have worsening of symptoms of SARS-CoV-2 infection within 48 hours after obtaining informed consent.
5)Patients with suspected active systemic bacterial, fungal, or viral infection requiring the treatment at randomization (excluding SARS-CoV-2)
6)Patients with renal or hepatic dysfunction who are receiving colchicine, patients with severe hepatic or renal dysfunction, or patients on dialysis.
7)Patients with a medical history of liver cirrhosis or liver decompensation (including ascites, variceal bleeding, or hepatic encephalopathy)
8)Patients with immunodeficiency
9)Patients who have difficulty entering subject diaries appropriately due to cognitive decline, etc.
10)Patients who used the following drugs within 15 days before randomization
-Approved treatment for SARS-CoV-2 infection
-Drugs with reported activity against SARS-CoV-2 (convalescent plasma, ivermectin, favipiravir, etc.)
11)Patients for whom the investigator (sub-investigator) determines that the use of prohibited drug is necessary during the study period.
12)Patients with substance abuse
13)Patients with a history of hypersensitivity or allergy to the study drug or its ingredients
14)Patients who is not able to swallow tablets or capsules.
15)Patients who have not passed 30 days or five times the half-lives since administration of an investigational drug or unapproved drug at the time of screening.
16)Patients who have been assigned to the study drug in this study.
17)Participants that the investigator(sub-investigator) deems difficult to be participated to the study.

Related Information

• Primary Sponsor: Mukae Hiroshi
• Secondary Sponsor: Shionogi & Co., Ltd.