Monkeypox
Conditions
Keywords
Monkeypox, MPXV
Brief summary
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
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 after discharge but while still enrolled in the study, they will be eligible to make a sick visit and will be offered standard of care for mpox.
Interventions
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)
DRUGPlacebo
Capsules to match tecovirimat
Sponsors
Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Lesion Resolution | Up to day 28 | Number of days from randomization to the first day on which all lesions on the total body are scabbed or desquamated or a new layer of epidermis has formed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Lesion Resolution for Participants With Symptom Onset Greater Than 7 Days Before Randomization | up to day 28 | 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. |
| Number and Percentage of Participants With Negative Blood PCR Results | day 14 | Percentage of participants with negative blood sample MPXV PCR results 14 days post-randomization, out of those positive at baseline |
| Number and Percentage of Participants With Negative Oropharyngeal Swab PCR Results | day 14 | Number and percentage of participants with negative oropharyngeal swab MPXV PCR results 14 days post-randomization, out of those positive at baseline |
| Number and Percentage of Participants With Negative Lesion Swab PCR Results | day 14 | Number and and percentage of participants with negative lesion swab MPXV PCR results 14 days post-randomization, of those positive at baseline |
| Time to Lesion Resolution for Participants With Symptom Onset Less Than or Equal to 7 Days Before Randomization | up to day 28 | 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. |
| Incidence of Non-fatal Serious Adverse Events Requiring Permanent Drug Discontinuation | Up to day 14 | Number of participants with a non-fatal serious adverse event requiring permanent drug discontinuation through the end of the treatment period (14 days) |
| Incidence of Non-fatal Adverse Events Requiring Permanent Drug Discontinuation | Up to day 14 | Number of participants with a non-fatal adverse event requiring permanent drug discontinuation through the end of the treatment period (14 days) |
| Incidence of Adverse Events | up to day 28 | Number of participants with an adverse event up to day 28 |
| Incidence of Bacterial Infection Adverse Events | up to day 28 | Number of participants with a bacterial infection adverse event up to day 28 |
| Mortality Within the First 28 Days Post-randomization | up to day 28 | Number of deaths post-randomization |
Countries
Democratic Republic of the Congo
Participant flow
Recruitment details
Patients were recruited from the areas surrounding two sites in rural Democratic Republic of the Congo - Tunda and Kole. Patient recruitment took place from October 2022 through July 9, 2024.
Participants by arm
| Arm | Count |
|---|---|
| Tecovirimat Tecovirimat capsules administered orally to participants for 14 days plus SOC. | 295 |
| Placebo Matching placebo capsules administered orally to participants for 14 days plus SOC. | 302 |
| Total | 597 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 5 | 4 |
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Tecovirimat |
|---|---|---|---|
| Age, Continuous | 15.3 Years STANDARD_DEVIATION 13.9 | 15.8 Years STANDARD_DEVIATION 13.9 | 16.4 Years STANDARD_DEVIATION 13.9 |
| Days since onset of symptoms | 5.9 Days STANDARD_DEVIATION 2.8 | 5.9 Days STANDARD_DEVIATION 2.6 | 5.9 Days STANDARD_DEVIATION 2.5 |
| Greater than 7 days since onset of symptoms | 63 Participants | 124 Participants | 61 Participants |
| Less than or equal to 7 days since onset of symptoms | 239 Participants | 473 Participants | 234 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 151 Participants | 292 Participants | 141 Participants |
| Sex: Female, Male Male | 151 Participants | 305 Participants | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 295 | 5 / 302 |
| other Total, other adverse events | 214 / 295 | 211 / 302 |
| serious Total, serious adverse events | 15 / 295 | 15 / 302 |
Outcome results
Primary
Time to Lesion Resolution
Number of days from randomization to the first day on which all lesions on the total body are scabbed or desquamated or a new layer of epidermis has formed.
Time frame: Up to day 28
Population: Intention to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tecovirimat | Time to Lesion Resolution | 7 Days |
| Placebo | Time to Lesion Resolution | 8 Days |
Secondary
Incidence of Adverse Events
Number of participants with an adverse event up to day 28
Time frame: up to day 28
Population: As-treated population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Incidence of Adverse Events | 196 Participants |
| Placebo | Incidence of Adverse Events | 199 Participants |
Secondary
Incidence of Bacterial Infection Adverse Events
Number of participants with a bacterial infection adverse event up to day 28
Time frame: up to day 28
Population: As-treated population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Incidence of Bacterial Infection Adverse Events | 23 Participants |
| Placebo | Incidence of Bacterial Infection Adverse Events | 27 Participants |
Secondary
Incidence of Non-fatal Adverse Events Requiring Permanent Drug Discontinuation
Number of participants with a non-fatal adverse event requiring permanent drug discontinuation through the end of the treatment period (14 days)
Time frame: Up to day 14
Population: As-treated population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Incidence of Non-fatal Adverse Events Requiring Permanent Drug Discontinuation | 1 Participants |
| Placebo | Incidence of Non-fatal Adverse Events Requiring Permanent Drug Discontinuation | 0 Participants |
Secondary
Incidence of Non-fatal Serious Adverse Events Requiring Permanent Drug Discontinuation
Number of participants with a non-fatal serious adverse event requiring permanent drug discontinuation through the end of the treatment period (14 days)
Time frame: Up to day 14
Population: As-treated population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Incidence of Non-fatal Serious Adverse Events Requiring Permanent Drug Discontinuation | 0 Participants |
| Placebo | Incidence of Non-fatal Serious Adverse Events Requiring Permanent Drug Discontinuation | 2 Participants |
Secondary
Mortality Within the First 28 Days Post-randomization
Number of deaths post-randomization
Time frame: up to day 28
Population: Intention to treat population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Mortality Within the First 28 Days Post-randomization | 3 Participants |
| Placebo | Mortality Within the First 28 Days Post-randomization | 4 Participants |
Secondary
Number and Percentage of Participants With Negative Blood PCR Results
Percentage of participants with negative blood sample MPXV PCR results 14 days post-randomization, out of those positive at baseline
Time frame: day 14
Population: Intention to treat population - participants with positive MPXV PCR in the blood at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Number and Percentage of Participants With Negative Blood PCR Results | 140 Participants |
| Placebo | Number and Percentage of Participants With Negative Blood PCR Results | 141 Participants |
Secondary
Number and Percentage of Participants With Negative Lesion Swab PCR Results
Number and and percentage of participants with negative lesion swab MPXV PCR results 14 days post-randomization, of those positive at baseline
Time frame: day 14
Population: Intention to treat population - participants with positive lesion swab MPXV PCR results at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Number and Percentage of Participants With Negative Lesion Swab PCR Results | 256 Participants |
| Placebo | Number and Percentage of Participants With Negative Lesion Swab PCR Results | 259 Participants |
Secondary
Number and Percentage of Participants With Negative Oropharyngeal Swab PCR Results
Number and percentage of participants with negative oropharyngeal swab MPXV PCR results 14 days post-randomization, out of those positive at baseline
Time frame: day 14
Population: Intention to treat population - participants with positive oropharyngeal swab MPXV PCR results at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Tecovirimat | Number and Percentage of Participants With Negative Oropharyngeal Swab PCR Results | 144 Participants |
| Placebo | Number and Percentage of Participants With Negative Oropharyngeal Swab PCR Results | 136 Participants |
Secondary
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.
Time frame: up to day 28
Population: Intention to treat population - participants with symptom onset greater than 7 days before randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tecovirimat | Time to Lesion Resolution for Participants With Symptom Onset Greater Than 7 Days Before Randomization | 8 Days |
| Placebo | Time to Lesion Resolution for Participants With Symptom Onset Greater Than 7 Days Before Randomization | 8 Days |
Secondary
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.
Time frame: up to day 28
Population: Intention to treat population - participants with symptom onset less than or equal to 7 days before randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tecovirimat | Time to Lesion Resolution for Participants With Symptom Onset Less Than or Equal to 7 Days Before Randomization | 7 Days |
| Placebo | Time to Lesion Resolution for Participants With Symptom Onset Less Than or Equal to 7 Days Before Randomization | 8 Days |