Study of Tecovirimat for Human Monkeypox Virus

Study Overview
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Brief Summary
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A5418 is a randomized, placebo-controlled, double-blind study to establish the efficacy of tecovirimat for the treatment of people with laboratory-confirmed or presumptive HMPXV disease.

Detailed Description
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Eligible and consented participants for the randomized arms (N=530) will be randomized 2:1 to receive either tecovirimat or placebo; participants with severe disease, significant skin conditions, participants with severe immune suppression will receive open-label tecovirimat. Participants who are pregnant or breastfeeding will receive open-label tecovirimat after discussion of the potential risks and benefits. Participants less than 18 years of age will receive open-label tecovirimat. Participants receiving a potent inducing concomitant medication will receive open-label tecovirimat. Once enrolled, study drug administration will be for 14 days. Participants who progress to severe HMPXV disease will be seen in person for a confirmation of progression. If severe disease is confirmed, participants will stop blinded study treatment and start a 14-day course of open-label tecovirimat. Participants reporting severe pain 5 days after randomization will stop blinded study treatment and start a 14-day course of open-label tecovirimat. Participants will self-monitor skin and/or mucosal lesions daily through 29 days or resolution (whichever comes first), complete a daily diary of symptoms and complete a daily numerical rating scale for pain assessment. Participants will be seen weekly through day 29 for assessment of HMPXV disease, safety assessments, HMPXV sampling similar to that described for entry, and swabbing of new HMPXV lesions. Participants will be seen at day 57 to assess for possible recrudescence of infection (i.e., new lesions occurring after initial resolution of disease.

Official Title
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A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Monkeypox Virus Disease

Conditions
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MPOX, Monkeypox

Intervention / Treatment
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* Drug: Tecovirimat Oral Capsule
* Drug: Placebo
* Drug: Tecovirimat Oral Capsule (Open Label)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (All participants; Arms A, B, and C): Laboratory-confirmed or presumptive HMPXV infection. HMPXV illness of <14 days duration immediately prior to study entry. At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers. Non-pregnant people of reproductive potential must agree to use at least one 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. Additional Inclusion Criteria for Arms A and B: 1. Age ≥18 years at the time of study entry Additional Inclusion Criteria for Arm C; Participants who meet the above entry criteria who also meet any of the following criteria will be registered to Arm C: Participants age <18 years at the time of study entry Those with severe HMPXV disease Those with or without severe disease and with one or more of the following will also be enrolled into Arm C: Severe immunosuppression Skin conditions placing the person at higher risk for disseminated infection Exclusion Criteria (All participants; Arms A, B, and C): Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism. Planned initiation of intramuscular cabotegravir/rilpivirine during study drug administration or for two weeks following completion of study drug administration. Participants who are stable on long-acting intramuscular cabotegravir/rilpivirine may enroll. Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study. Participants who require intravenous dosing of tecovirimat.
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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br> | Drug: Tecovirimat Oral Capsule<br>* Drug: Tecovirimat Oral capsules Participants weighing 25 kg to less than 40 kg - Tecovirimat 400 mg every 12 hours for 14 days Participants weighing 40 kg to less than 120 kg - Tecovirimat 600 mg every 12 hours for 14 days Participants weighing 120 kg and over - Tecovirimat 600 mg every 8 hours for 14 days<br>|
| Placebo Comparator: Arm B<br> | Drug: Placebo<br>* Drug: Placebo Oral capsules Participants weighing 25 kg to less than 40 kg - Placebo for Tecovirimat 400 mg every 12 hours for 14 days Participants weighing 40 kg to less than 120 kg - Placebo for Tecovirimat 600 mg every 12 hours for 14 days Participants weighing 120 kg and over - Placebo for Tecovirimat 600 mg every 8 hours for 14 days<br>|
| Experimental: Arm C<br> | Drug: Tecovirimat Oral Capsule (Open Label)<br>* Participants weighing 4 to <6kg and >7 days old - Tecovirimat 50mg every 12 hours for 14 days Participants weighing 2.5 to <4kg and >7 days to <4 weeks old - Tecovirimat 20 mg every 12 hours for 14 days Participants weighing 4 to <6kg and ≤7 days old - Tecovirimat 50mg every 24 hours for 14 days Participants weighing 2.5 to <4 kg and ≤7 days old - Tecovirimat 20mg every 24 hours for 14 days Participants weighing 6 kg to less than 13 kg - Tecovirimat 100 mg every 12 hours for 14 days Participants weighing 13 kg to less than 25 kg - Tecovirimat 200 mg every 12 hours for 14 days Participants weighing 25 kg to less than 40 kg - Tecovirimat 400 mg (2 capsules) every 12 hours for 14 days Participants weighing 40 kg to less than 120 kg - Tecovirimat 600 mg every 12 hours for 14 days Participants weighing 120 kg and over - Tecovirimat 600 mg every 8 hours for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical resolution, defined as the first day on which all skin lesions are scabbed, desquamated or healed, and visible mucosal lesions are healed |  | Up to day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain assessed by 11-point numerical rating scale for pain |  | Through day 29 | 
| Time to development of severe HMPXV in those without severe HMPXV at baseline |  | Through day 57 | 
| Level of HMPXV in blood |  | Through day 57 | 
| Level of HMPXV in skin lesions |  | Through day 57 | 
| Level of HMPXV in oropharynx |  | Through day 57 | 
| Level of HMPXV in rectum |  | Through day 57 | 
| Level of HMPXV in genital secretions |  | Through day 57 | 
| Time to complete lesion healing defined as all lesions being re-epithelialized |  | Up to day 29 | 
| Participant-reported adherence |  | Through day 15 | 
| Participant-reported quality-of-life as measured by EQ-5D-5L |  | Through day 29 | 
| Occurrence of Grade 3 or greater adverse event |  | Through day 57 | 
| All-cause mortality |  | Through day 57 | 
| Tecovirimat concentrations in blood in children less than 18 years of age |  | Through day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HMPXV