Clinical trial NCT06721585: Tecovirimat for Treatment of Monkeypox Virus - Study Extension Providing Standard of Care Only
Official title: 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 - Extension Amendment
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Mpox (Monkeypox)
Keywords: Mpox
MPXV
Monkeypox
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
First posted: 2024-12-06
Enrollment: 400
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults and children with laboratory-confirmed monkeypox virus (MPXV) disease at participating sites in the Democratic Republic of Congo

Brief summary: The purpose of the PALM007 extension is to further characterize the clinical and natural history of mpox, and to provide standard of care (SOC) during the ongoing outbreaks.

Detailed description: This open-label extension to the PALM007 protocol began in July 2024 after enrollment into the main study ended. It will further clinically characterize the natural history of mpox, and continue to identify recrudescent cases. Participants were initially provided SOC as well as open-access tecovirimat. The results of PALM007 were unblinded in August 2024, and although no safety concerns were observed with tecovirimat use, efficacy, defined by improvement in days to complete mpox skin lesion resolution, was not observed for tecovirimat compared to placebo. Therefore, the administration of tecovirimat in the extension amendment was discontinued in early August 2024, once these results were known, and only SOC continues to be provided.

Participants are admitted to the hospital and receive SOC for mpox until they have recovered. Recovery is defined as resolution of all lesions and a negative blood test for MPXV. Participants will remain on study through day 59 but will not have a scheduled study visit unless they present with new mpox symptoms. Sick visits will be available for participants who reach full body lesion resolution but subsequently develop at least 1 new lesion consistent with mpox after discharge and on or before day 59, at which time viral PCR and clinical laboratory testing will be performed and participants will be offered standard of care.

Initially, all participants presenting with mpox were eligible to enroll in this extension, regardless of disease severity. As of 05May2025, only patients with severe disease, defined as the presence of any of the following: flat lesions, pregnancy (due to risk for serious complications), suspected sickle cell disease, or severe clinical disease will be enrolled.

Eligibility criteria: This study has no age restriction

Inclusion Criteria:

1. Laboratory-confirmed mpox infection as determined by PCR obtained from blood, oropharynx, or skin lesion within 48 hours of screening
2. Mpox illness of any duration provided that the patient has at least one active, not yet scabbed, lesion
3. Stated willingness to comply with all study procedures (including required inpatient stay) and availability for the duration of the study
4. Ability to provide informed consent personally or by a legally or culturally acceptable representative if the patient is unable to do so
5. Severe disease, defined as the presence of at least one of the following:

   1. Flat lesions (flat and soft lesions; no pustules or vesicles visible to the eye)
   2. Pregnancy (due to risk of serious complication)
   3. Suspected sickle cell disease
   4. Severe clinical disease, defined as having at least 3 of the following:

      * Lesion count greater than 250
      * Fever for greater than 48 hours
      * Hypotension (systolic blood pressure less than 90 mmHg or diastolic blood pressure less than 60 mmHg)
      * Pallor
      * Respiratory distress
      * Altered mental status
      * Extreme lethargy
      * Painful oral lesions making oral intake difficult
      * Difficulty peeing or pooping due to painful lesions
      * Painful lesions on hands and feet
      * Tachycardia (heart rate greater than 100 beats per minute)
      * Diarrhea (greater than or equal to 3 liquid stools per 24 hours)

Exclusion Criteria:

1. Severe anemia, defined as hemoglobin less than 7 g/dL
2. Current or planned use of another investigational drug at any point during study participation
3. Patients who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study

Primary outcomes:
measure: Time to lesion resolution
timeFrame: up to day 28
Secondary outcomes:
measure: Time to lesion resolution for participants with symptom onset less than or equal to 7 days enrollment
timeFrame: up to day 28
measure: Time to lesion resolution for participants with symptom onset greater than 7 days before enrollment
timeFrame: up to day 28
measure: Number of participants that develop at least 1 new mpox lesion after discharge
timeFrame: up to day 59
measure: Mortality within the first 28 days post-enrollment
timeFrame: up to day 28
measure: Number of days to participant death
timeFrame: up to day 59
measure: Frequency of solicited clinical symptoms
timeFrame: up to day 59
measure: Duration of solicited clinical symptoms
timeFrame: up to day 59
Other outcomes:
Locations:
city: Kole
country: Congo, The Democratic Republic of the
facility: L'Hôpital Général de Référence de Kole
city: Tunda
country: Congo, The Democratic Republic of the
facility: L'Hôpital Général de Référence de Tunda
Study officials:
affiliation: Kinshasa University
name: Jean-Jacques Muyembe-Tamfum, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: