Tecovirimat for Treatment of Monkeypox Virus

Study Overview
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Brief Summary
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The purpose of this study is to find out if tecovirimat is a safe and effective drug to treat monkeypox (mpox) in combination with standard of care (SOC). Participants will be randomly assigned to receive oral tecovirimat plus SOC or placebo plus SOC for 14 days.

Detailed Description
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This is a randomized, placebo-controlled, double-blind study to test the antiviral drug tecovirimat for the treatment of adults and children with laboratory-confirmed monkeypox virus (MPXV) disease at participating sites in the Democratic Republic of Congo. Eligible and consented participants will be randomized 1:1 to receive either oral tecovirimat or placebo, each administered in the hospital with standard-of-care (SOC) treatment for 14 days. Participants will be followed for 28 days with an optional visit at Day 59 for long-term assessment. If a participant reaches full body lesion resolution but subsequently develops at least one new lesion consistent with mpox while still enrolled in the study, they will be eligible to make a sick visit and will be offered standard of care.

Official Title
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A Randomized, Placebo-controlled, Double-blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Adult and Pediatric Patients With Monkeypox Virus Disease

Conditions
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Monkeypox

Intervention / Treatment
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* Drug: Tecovirimat Oral Capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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This study has no age restriction. Inclusion Criteria: Laboratory-confirmed monkeypox virus infection as determined by PCR obtained from blood, oropharynx, or skin lesion within 48 hours of screening Monkeypox illness of any duration provided that the patient has at least one active, not yet scabbed, lesion Weight ≥3 kg Men and non-pregnant women of reproductive potential must agree to use effective means of contraception when engaging in sexual activities that can result in pregnancy, from the time of enrollment through the end of study participation. Acceptable methods of contraception include the following: Hormonal contraception Male or female condom Diaphragm or cervical cap with a spermicide Intrauterine device Stated willingness to comply with all study procedures (including required inpatient stay) and availability for the duration of the study Ability to provide informed consent personally or by a legally or culturally acceptable representative if the patient is unable to do so Exclusion Criteria: Current or planned use of a meglitinide (repaglinide, nateglinide) Planned use of midazolam while on study drug Severe anemia, defined as hemoglobin <7 g/dL Current or planned use of another investigational drug at any point during study participation Patients who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study Participants who are unable to safely swallow oral medications, such as those who are at risk of aspiration
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tecovirimat<br>Tecovirimat capsules administered orally to participants for 14 days plus SOC. | Drug: Tecovirimat Oral Capsule<br>* 200 mg capsules Number of capsules and frequency of dosage will be based on participant weight: ≥120 kg: three capsules three times a day (total daily tecovirimat dose: 1,800 mg) 40 to <120 kg: three capsules twice a day (total daily tecovirimat dose: 1,200 mg) 25 to <40 kg: two capsules twice a day (total daily tecovirimat dose: 800 mg) 13 to <25 kg: one capsule twice a day (total daily tecovirimat dose: 400 mg) 6 to <13 kg: ½ the contents of a capsule twice daily (total daily tecovirimat dose: 200 mg) 3 to <6 kg: ¼ the contents of a capsule twice daily (total daily tecovirimat dose: 100 mg)<br>* Other names: TPOXX;|
| Placebo Comparator: Placebo<br>Matching placebo capsules administered orally to participants for 14 days plus SOC. | Drug: Placebo<br>* Capsules to match tecovirimat<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to lesion resolution | Number of days to the first day on which all lesions on the total body are scabbed or desquamated or a new layer of epidermis has formed. | up to day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to lesion resolution for participants with symptom onset less than or equal to 7 days before randomization | Number of days to the first day on which all lesions on the total body are scabbed or desquamated or a new layer of epidermis has formed. | up to day 28 | 
| Time to lesion resolution for participants with symptom onset greater than 7 days before randomization | Number of days to the first day on which all lesions on the total body are scabbed or desquamated or a new layer of epidermis has formed. | up to day 28 | 
| Number of participants with negative blood PCR results | Proportion of participants with negative blood sample MPXV PCR results 14 days post-randomization | day 14 | 
| Number of participants with negative oropharyngeal swab PCR results | Proportion of participants with negative oropharyngeal swab MPXV PCR results 14 days post-randomization | day 14 | 
| Number of participants with negative lesion swab PCR results | Proportion of participants with negative lesion swab MPXV PCR results 14 days post-randomization | day 14 | 
| Mortality within the first 28 days post-randomization | Number of deaths post-randomization | up to day 28 | 
| Number of days to participant death | Number of days post-randomization | up to day 28 | 
| Frequency of solicited clinical symptoms | Clinical symptoms defined as: nausea, vomiting, abdominal pain, diarrhea, anorexia, cough, lymphadenopathy, dysphagia, sore throat, muscle aches, fatigue/lack of energy, fever, chills, night sweats, headache, ocular lesions, eye pain, change in vision, buccal ulcers, nasal congestion, cough, joint pain, pain with urination, painful skin lesions, pruritic skin lesions. | up to day 59 | 
| Duration of solicited clinical symptoms | Number of days | up to day 59 | 
| Incidence of serious adverse events requiring drug discontinuation | Number of SAEs | up to day 14 | 
| Incidence of adverse events requiring drug discontinuation | Number of AEs | up to day 14 | 
| Incidence of other adverse events | Number of AEs | up to day 28 | 
| Incidence of bacterial infections | Number of clinically defined bacterial infections. Laboratory and radiographical confirmation when possible. | up to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monkeypox, MPXV