European Trial Into Mpox Infection

Study Overview
=================
Brief Summary
-----------------
The goal of this randomized controlled double-blind clinical trial is to test the drug tecovirimat in patients with mpox (previously known as monkeypox) disease. The main questions it aims to answer are: Is tecovirimat effective in treating mpox infection. Is tecovirimat safe to treat patients with mpox infection. Participants will receive either the drug tecovirimat orally, 600 mg twice per day, or a matching placebo. The outcome of the infection and the side effect experienced will be compared between the two groups.

Official Title
-----------------
European Randomised Clinical Trial on mPOX Infection

Conditions
-----------------
Monkeypox

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Polymerase Chain Reaction (PCR) /Nucleic Acid Amplification Test (NAAT) -confirmed mpox infection The presence of active skin or mucosal lesion(s) Signed Informed Consent Form Exclusion Criteria: Age <18 years. Body weight <40 kg Pregnant and breastfeeding patients are not eligible for inclusion in this study. Lack of mental capacity to provide informed consent Trial participation is considered not in the best interest of patient Known hypersensitivity to the active substance or to any of the excipients of the study drug. Use of contraindicated treatment repaglinide. (Repaglinide, an oral treatment for diabetes mellitus, may be discontinued while taking study treatment with the agreement of the patient's general practitioner, who may start alternate diabetes treatment if considered necessary.) Previous, current or planned use of another investigational drug (tecovirimat) at any point during study participation. The patient's own doctor considers there to be a definite indication for the patient to receive tecovirimat or the local guidelines establish that tecovirimat treatment should be initiated The patient's own doctor considers there to be a definite contraindication to the patient receiving tecovirimat. The patient suffers from hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tecovirimat<br>Oral treatment with tecovirimat 200 mg capsules. Twice daily three capsules orally. Duration of treatment: 14 days (28 administrations). | Drug: Tecovirimat Oral Capsule<br>* 600 mg, twice daily, 14 days.<br>* Other names: Tpoxx Tecovirimat;|
| Placebo Comparator: Placebo<br>Matching placebo to tecovirimat capsules. Twice daily three capsules orally. Duration of treatment: 14 days (28 administrations). | Drug: Placebo<br>* 3 capsules, twice daily, 14 days.<br>* Other names: Oral placebo capsule;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to complete mpox lesion resolution | Time in days until day 28 after randomization, until the first day on which all lesions are completely healed with a new fresh layer of skin. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to active lesion resolution | The first day on which all skin lesions are scabbed or desquamated (and mucosal lesions healed), counted from start of therapy, with follow-up up to 28 days after randomisation | 28 days | 
| Status of the lesions on day 7, 14 and 28 | Status of the lesions on day 7, 14, 21 and 28 according to an ordinal scale. The ordinal scale is a) all lesions completely resolved (all scabs dropped off and intact skin remains underneath, and all mucosal lesions healed), b) active lesions resolved (all skin lesions scabbed or desquamated, but not fully resolved), c) active lesions persist but no new lesions in last 24 hours, d) new lesion(s) in last 24 hours. | Day 7, day 14 and day 28 | 
| Time to resolution of symptoms | Time to resolution of symptoms. Symptoms are counted from start of therapy and assessed by self-assessment. These include fatigue, malaise, nausea, vomiting, abdominal pain, anorexia, cough, dysphagia, odynophagia, fever, headache, oral pain, pain with urination, rectal/anal pain. Signs will be evaluated at study visits only, including lymphadenopathy and proctitis, and are not included in the evaluation of symptoms. | 90 days | 
| Occurrence of a negative monkeypox PCR of skin or mucosal swab | Negative monkeypox PCR (Polymerase Chain Reaction) of skin or mucosal swab, assessed for the two most active skin lesions or for the mucosal lesion. | Days 7, 14 and 28 | 
| Persistence of scars and skin discoloration | Assessment of scars and/or skin discoloration of mpox lesions. | Assessed on day 90 | 
| Change from baseline in quality of life | Change from baseline of quality of life, assessed by the Dermatology Life Quality Index (DLQI). Minimum value = 0, maximum value = 30, a higher score indicates a worse outcome. (Ten questions with each a minimum of 0 and a maximum of 3.) | Assessed on day 14 and day 90. | 
| All-cause mortality | All-cause mortality | Assessed on day 28 and on day 90 | 
| Time to complication or all-cause admission to hospital or all-cause death | Time to complication or all-cause admission to hospital or all-cause death, within 28 days and within 90 days, applicable to outpatients only, and counted from start of therapy. A complication includes genitourinary complications (e.g. urinary retention, paraphimosis), lower respiratory tract complication (e.g. pneumonia and need for oxygen), ocular impairment (e.g. keratitis), neurologic impairment (e.g. encephalitis) or mental health disturbance (e.g. confusion), cardiac impairment (e.g. cardiomyopathy or myocarditis), severe dehydration needing admission, secondary bacterial skin infection or severe pain needing hospital admission. | Assessed within 28 days and within 90 days. | 
| Frequency of AEs, SAEs and SUSARs | Frequency of Adverse Events (AEs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reaction (SUSARs) for the specific therapeutic, within the first 28 days, but also assessed during the total follow-up (up to day 90). | Assessed within 28 days and within 90 days. | 
| Resolution of pain | Resolution of pain, by measuring: time to resolution of pain assessed by the Numeric Rating Scale (NRS) for pain, time to cessation of the use of analgesic medication, defined as time to consistently reporting no use of analgesia for mpox-related lesions, up to 90 days after randomisation. anal pain on days 7, 14, and 90 assessed by the Health Related Symptom Index. | Assessed on days 7, 14 and 90. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
tecovirimat, mpox, TPOXX