A Phase 3 interventional study of Tecovirimat Oral Capsule and Placebo for Tecovirimat in MPOX, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 54 sites in 6 countries. Per ClinicalTrials.gov, last updated 2026-06-23.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 3, Interventional, and Treatment
The purpose of this study was to see if tecovirimat is safe and successful at treating mpox. The main questions were whether tecovirimat reduced time to lesion resolution and pain compared to placebo (no treatment).
This phase 3, randomized, placebo-controlled, double-blind clinical trial evaluated the efficacy of tecovirimat for the treatment of mpox. Participants who had or were at higher risk for severe disease because of their age or medical history, were pregnant or breastfeeding, or were taking medications that could have decreased their exposure to tecovirimat were assigned to receive open-label tecovirimat for 14 days. All other participants were randomized 2:1 to receive either tecovirimat or placebo for 14 days.
Randomized participants who reported severe pain 5 days after randomization (on Day 6) or later or progressed to severe disease stopped blinded study treatment and started a 14-day course of open-label tecovirimat.
Participants self-monitored lesions daily through 28 days (Day 29) or resolution, whichever came first, and completed a daily pain scale and symptom diary. Study visits occurred weekly through 28 days (Day 29) and included safety and skin assessments and specimen collections. A final study visit occurred at 56 days (Day 57) to assess for recrudescence of infection (development of new lesions after initial resolution of disease).
Version 3 of the protocol gave participants the option to enroll and complete study visits remotely. Participants did not provide specimens at remote visits.
On November 26, 2024, the Data and Safety Monitoring Board (DSMB) recommended that the study close due to statistical futility. The study team and sponsor agreed with the DSMB's recommendation and the study closed to accrual on November 27, 2024. The primary analysis report forming the basis of the primary manuscript used data from follow-up visits occurring through October 23, 2024, the data cutoff for the November 2024 DSMB review (the primary completion date). Outcome measures submitted to clinicaltrials.gov were also based on data from follow-up visits occurring through October 23, 2024, and summaries of participant flow, baseline characteristics, and adverse events submitted to clinicaltrials.gov were based on data from follow-up visits occurring through February 22, 2025 (the study completion date).
72 studies on the registry are indexed under Mpox, Monkeypox; 30 are open to participants now.
This study's enrollment of 719 is above the median of 305 across 36 interventional studies indexed under Mpox, Monkeypox.
Browse Mpox, Monkeypox studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria (All participants; Arms A, B, and C):
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.
Those with severe HMPXV disease defined as having one or more of the following conditions:
Those with or without severe disease and with one or more of the following:
Exclusion Criteria (All participants; Arms A, B, and C):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants randomized to tecovirimat.
Drug: Tecovirimat Oral Capsule
Participants randomized to placebo.
Drug: Placebo for Tecovirimat
Participants assigned to open-label tecovirimat.
Drug: Tecovirimat Oral Capsule (Open Label)
* 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
* 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
* Participants weighing \<3 kg - Tecovirimat 33.3 mg every 12 hours for 14 days * Participants weighing 3 kg to less than 6 kg- Tecovirimat 50 mg every 12 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 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
Cumulative Proportion With Clinical Resolution by Day 29
Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution was estimated using the Aalen-Johansen estimator. The treatment effect, i.e., the subdistribution hazard ratio of tecovirimat relative to placebo, was estimated using the Fine and Gray subdistribution proportional hazards model. All-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: From study entry through 28 days of follow-up (i.e., Day 29)
Mean Time-weighted Average of Pain Intensity Difference Over 5 Days of Treatment
Pain was measured on 11-point numerical rating scale (NRS) where 0 = no pain and 10 = worst possible pain. Pain intensity difference at ith day of treatment (i = 2, ..., 6) calculated as NRS pain score at baseline (last available pre-treatment) minus NRS pain score on ith day of treatment Time-weighted average of pain intensity difference over 5 days of treatment was a weighted average of the pain intensity difference from treatment day 2 to treatment day 6, where the weights were calculated as the duration in days between the ith day of treatment and the day of the previous measurement. The lowest possible value that this could have been was -10, which would have indicated an increase in pain by 10 points on average over 5 days of treatment. The highest possible value that this could have been was +10, which would have indicated a decrease in pain by 10 points on average over 5 days of treatment. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Through 5 days of treatment (i.e., Treatment Day 6)
Mean Time-weighted Average of Pain Intensity Difference Over 14 Days of Treatment
Pain was measured on 11-point numerical rating scale (NRS) where 0 = no pain and 10 = worst possible pain. Pain intensity difference at ith day of treatment (i = 2, ..., 15) calculated as NRS pain score at baseline (last available pre-treatment) minus NRS pain score on ith day of treatment Time-weighted average of pain intensity difference over 14 days of treatment was a weighted average of the pain intensity difference from treatment day 2 to treatment day 15, where the weights were calculated as the duration in days between the ith day of treatment and the day of the previous measurement. The lowest possible value that this could have been was -10, which would have indicated an increase in pain by 10 points on average over 5 days of treatment. The highest possible value that this could have been was +10, which would have indicated a decrease in pain by 10 points on average over 5 days of treatment. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Through 14 days of treatment (i.e., Treatment Day 15)
Number of Participants Who Developed Severe HMPXV Disease
Severe HMPXV disease was defined as one or more of the following conditions: suspected or confirmed ocular involvement, facial lesions on the malar, nose, or eyelid region, confluent facial lesions, hospitalization due to HMPXV infection or its complications, or lesions that required surgical intervention including debridement, urinary catheterization, or sigmoidoscopy, or extended below the dermis.
Time frame: From study entry through 56 days of follow-up (i.e., Day 57)
Number of Participants With HMPXV DNA Below Limit of Detection in Skin Lesions
HMPXV DNA was measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, 22, 29, and 57
Number of Participants With HMPXV DNA Below Limit of Detection in Oropharynx
HMPXV DNA was measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, 22, 29, and 57
Number of Participants With HMPXV DNA Below Limit of Detection in Rectum
HMPXV DNA was measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, 22, 29, and 57
Number of Participants With HMPXV DNA Below Limit of Detection in Blood
HMPXV DNA measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, 22, 29, and 57
Number of Participants With HMPXV DNA Below Limit of Detection in Vaginal Swabs
HMPXV DNA measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, 22, 29, and 57
Cumulative Proportion With Complete Lesion Healing by Day 29
Complete lesion healing was defined as all lesions re-epithelialized. The cumulative incidence of complete lesion healing was estimated using the Aalen-Johansen estimator. The treatment effect, i.e., the subdistribution hazard ratio of tecovirimat relative to placebo, was estimated using the Fine and Gray subdistribution proportional hazards model. All-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: From study entry through 28 days of follow-up (i.e., Day 29)
Number of Participants With no Missed Doses (of Last Three Prescribed Doses)
Since the adherence assessment was removed from protocol version 3.0, the number of participants with adherence data was expected to be small and no formal statistical comparison between treatment arms was done. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Days 8 and 15
Median Change From Baseline in EuroQol (EQ) Visual Analogue Scale (VAS) Score
Participants' self-rated health measured on a visual analogue scale (VAS) where 0 = "The worst health you can imagine" and 100 = "The best health you can imagine." Change in EQ VAS score at each timepoint calculated as absolute change from baseline (last available pre-treatment). Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Days 8, 15, and 29
Number of Participants Who Reported Each Level of Response on Mobility Dimension of EuroQol EQ-5D-5L Questionnaire
Participants' self-reported health state within mobility dimension of the five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, and 29
Number of Participants Who Reported Each Level of Response on Self-Care Dimension of EuroQol EQ-5D-5L Questionnaire
Participants' self-reported health state within self-care dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, and 29
Number of Participants Who Reported Each Level of Response on Usual Activities Dimension of EuroQol EQ-5D-5L Questionnaire
Participants' self-reported health state within usual activities dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, and 29
Number of Participants Who Reported Each Level of Response on Pain/Discomfort Dimension of EuroQol EQ-5D-5L Questionnaire
Participants' self-reported health state within pain/discomfort dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, and 29
Number of Participants Who Reported Each Level of Response on Anxiety/Depression Dimension of EuroQol EQ-5D-5L Questionnaire
Participants' self-reported health state within anxiety/depression dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Baseline, Days 8, 15, and 29
Proportion of Participants With Grade 3 or Greater Treatment-emergent Adverse Event
Study protocol required reporting of all adverse events (AEs) that (1) led to a change in study treatment regardless of grade, (2) met the serious AE (SAE) or Expedited AE (EAE) reporting requirement, and (3) were Grade 3 or greater. AEs were graded using the DAIDS AE Grading Table (Version 2.1). Severity Grade: 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Life-Threatening, 5 = Death Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Through 56 days of follow-up (i.e., Day 57)
Number of Participants Who Died From Any Cause
Includes data from follow-up visits occurring through October 23, 2024.
Time frame: Through 56 days of follow-up (i.e., Day 57)
Tecovirimat Concentrations in Children Less Than 18 Years of Age
Plasma tecovirimat concentrations were quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. The lower limit of quantification was 5.0 ng/mL.
Time frame: On Day 8, blood samples were collected pre-dose and at 1, 2, 3, 4, 6, 8, and 10 hours post-dose. On Day 15, a single blood sample was collected within 4 hours of study product administration.
Cumulative Proportion With Clinical Resolution by Day 29 by Sex
NIH-required analysis. Subgroup analysis of the primary outcome measure by sex. Interaction of treatment and sex was not tested because of the small number of females enrolled. Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution in the presence of competing events was estimated using the Aalen-Johansen estimator, where all-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: From study entry through 28 days of follow-up (i.e., Day 29)
Cumulative Proportion With Clinical Resolution by Day 29 by Race
NIH-required analysis. Subgroup analysis of the primary outcome measure by race (White, Non-White). "Non-White" includes participants who identified as Black or African American, Asian, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, "other" race, having more than one race, or having unknown race. Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution in the presence of competing events was estimated using the Aalen-Johansen estimator, where all-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: From study entry through 28 days of follow-up (i.e., Day 29)
Cumulative Proportion With Clinical Resolution by Day 29 by Ethnicity
NIH-required analysis. Subgroup analysis of the primary outcome measure by ethnicity (Hispanic or Latino, Not Hispanic or Latino). Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution in the presence of competing events was estimated using the Aalen-Johansen estimator, where all-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
Time frame: From study entry through 28 days of follow-up (i.e., Day 29)
Participants were enrolled at 58 clinical research sites in 7 countries (United States, Peru, Mexico, Thailand, Argentina, Japan, and Brazil) from September 2022 to November 2024.
| Milestone | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Started | 290 | 148 | 281 |
| Started treatment | 290 | 146 | 281 |
| Started open-label tecovirimat | 23 | 13 | 281 |
| Completed | 231 | 112 | 233 |
| Not completed | 59 | 36 | 48 |
| Withdrew: Negative for hmpxv | 30 | 21 | 20 |
| Withdrew: Lost to follow-up | 23 | 11 | 26 |
| Withdrew: Withdrawal by subject | 6 | 3 | 2 |
| Withdrew: Adverse event | 0 | 1 | 0 |
Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution was estimated using the Aalen-Johansen estimator. The treatment effect, i.e., the subdistribution hazard ratio of tecovirimat relative to placebo, was estimated using the Fine and Gray subdistribution proportional hazards model. All-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
| cumulative proportion of participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Cumulative Proportion With Clinical Resolution by Day 29 | 0.83 (0.77 to 0.87) | 0.84 (0.76 to 0.90) | 0.85 (0.79 to 0.90) |
Pain was measured on 11-point numerical rating scale (NRS) where 0 = no pain and 10 = worst possible pain. Pain intensity difference at ith day of treatment (i = 2, ..., 6) calculated as NRS pain score at baseline (last available pre-treatment) minus NRS pain score on ith day of treatment Time-weighted average of pain intensity difference over 5 days of treatment was a weighted average of the pain intensity difference from treatment day 2 to treatment day 6, where the weights were calculated as the duration in days between the ith day of treatment and the day of the previous measurement. The lowest possible value that this could have been was -10, which would have indicated an increase in pain by 10 points on average over 5 days of treatment. The highest possible value that this could have been was +10, which would have indicated a decrease in pain by 10 points on average over 5 days of treatment. Includes data from follow-up visits occurring through October 23, 2024.
| score on a scale | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Mean Time-weighted Average of Pain Intensity Difference Over 5 Days of Treatment | 3.2 ± 2.1 | 3.1 ± 2.0 | 3.6 ± 2.1 |
Pain was measured on 11-point numerical rating scale (NRS) where 0 = no pain and 10 = worst possible pain. Pain intensity difference at ith day of treatment (i = 2, ..., 15) calculated as NRS pain score at baseline (last available pre-treatment) minus NRS pain score on ith day of treatment Time-weighted average of pain intensity difference over 14 days of treatment was a weighted average of the pain intensity difference from treatment day 2 to treatment day 15, where the weights were calculated as the duration in days between the ith day of treatment and the day of the previous measurement. The lowest possible value that this could have been was -10, which would have indicated an increase in pain by 10 points on average over 5 days of treatment. The highest possible value that this could have been was +10, which would have indicated a decrease in pain by 10 points on average over 5 days of treatment. Includes data from follow-up visits occurring through October 23, 2024.
| score on a scale | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Mean Time-weighted Average of Pain Intensity Difference Over 14 Days of Treatment | 4.8 ± 2.2 | 4.9 ± 2.1 | 5.5 ± 2.0 |
Severe HMPXV disease was defined as one or more of the following conditions: suspected or confirmed ocular involvement, facial lesions on the malar, nose, or eyelid region, confluent facial lesions, hospitalization due to HMPXV infection or its complications, or lesions that required surgical intervention including debridement, urinary catheterization, or sigmoidoscopy, or extended below the dermis.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Number of Participants Who Developed Severe HMPXV Disease | 9 | 6 | 1 |
HMPXV DNA was measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline | 18 | 12 | 23 |
| Day 8 | 68 | 26 | 66 |
| Day 15 | 106 | 53 | 122 |
| Day 22 | 110 | 59 | 105 |
| Day 29 | 112 | 64 | 102 |
| Day 57 | 115 | 60 | 92 |
HMPXV DNA was measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline | 85 | 45 | 48 |
| Day 8 | 137 | 67 | 140 |
| Day 15 | 132 | 68 | 142 |
| Day 22 | 121 | 63 | 115 |
| Day 29 | 123 | 64 | 107 |
| Day 57 | 120 | 61 | 95 |
HMPXV DNA was measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline | 46 | 26 | 39 |
| Day 8 | 108 | 48 | 91 |
| Day 15 | 134 | 64 | 120 |
| Day 22 | 124 | 63 | 103 |
| Day 29 | 123 | 65 | 103 |
| Day 57 | 120 | 60 | 88 |
HMPXV DNA measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline | 69 | 45 | 40 |
| Day 8 | 139 | 65 | 127 |
| Day 15 | 136 | 65 | 133 |
| Day 22 | 122 | 62 | 106 |
| Day 29 | 125 | 67 | 105 |
| Day 57 | 118 | 62 | 99 |
HMPXV DNA measured as detected or below limit of detection. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline | 0 | 0 | 1 |
| Day 8 | 1 | 0 | 2 |
| Day 15 | 1 | 0 | 2 |
| Day 22 | 3 | 1 | 3 |
| Day 29 | 4 | 1 | 3 |
| Day 57 | 3 | 1 | 2 |
Complete lesion healing was defined as all lesions re-epithelialized. The cumulative incidence of complete lesion healing was estimated using the Aalen-Johansen estimator. The treatment effect, i.e., the subdistribution hazard ratio of tecovirimat relative to placebo, was estimated using the Fine and Gray subdistribution proportional hazards model. All-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
| cumulative proportion of participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Cumulative Proportion With Complete Lesion Healing by Day 29 | 0.75 (0.68 to 0.80) | 0.75 (0.66 to 0.83) | 0.69 (0.62 to 0.75) |
Since the adherence assessment was removed from protocol version 3.0, the number of participants with adherence data was expected to be small and no formal statistical comparison between treatment arms was done. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Day 8 — 0 missed doses | 43 | 18 | 27 |
| Day 8 — 1 missed doses | 0 | 0 | 1 |
| Day 8 — 2 missed doses | 1 | 2 | 0 |
| Day 8 — 3 missed doses | 1 | 1 | 0 |
| Day 15 — 0 missed doses | 36 | 16 | 24 |
| Day 15 — 1 missed doses | 1 | 1 | 2 |
| Day 15 — 2 missed doses | 0 | 0 | 1 |
| Day 15 — 3 missed doses | 0 | 0 | 0 |
Participants' self-rated health measured on a visual analogue scale (VAS) where 0 = "The worst health you can imagine" and 100 = "The best health you can imagine." Change in EQ VAS score at each timepoint calculated as absolute change from baseline (last available pre-treatment). Includes data from follow-up visits occurring through October 23, 2024.
| score on a scale | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Day 8 | 10 (0 to 20) | 10 (5 to 25) | 15 (5 to 30) |
| Day 15 | 20 (5 to 35) | 20 (10 to 30) | 25 (10 to 40) |
| Day 29 | 20 (10 to 35) | 24.5 (10 to 30) | 25 (10 to 45) |
Participants' self-reported health state within mobility dimension of the five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline — No problems | 169 | 86 | 153 |
| Baseline — Any problems | 58 | 28 | 71 |
| Day 8 — No problems | 197 | 98 | 180 |
| Day 8 — Any problems | 21 | 8 | 39 |
| Day 15 — No problems | 184 | 96 | 188 |
| Day 15 — Any problems | 6 | 1 | 14 |
| Day 29 — No problems | 170 | 83 | 176 |
| Day 29 — Any problems | 8 | 2 | 15 |
Participants' self-reported health state within self-care dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline — No problems | 177 | 86 | 170 |
| Baseline — Any problems | 49 | 28 | 54 |
| Day 8 — No problems | 203 | 99 | 195 |
| Day 8 — Any problems | 15 | 7 | 24 |
| Day 15 — No problems | 184 | 94 | 186 |
| Day 15 — Any problems | 6 | 3 | 16 |
| Day 29 — No problems | 174 | 83 | 185 |
| Day 29 — Any problems | 4 | 2 | 6 |
Participants' self-reported health state within usual activities dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline — No problems | 140 | 72 | 123 |
| Baseline — Any problems | 87 | 42 | 101 |
| Day 8 — No problems | 171 | 88 | 164 |
| Day 8 — Any problems | 47 | 18 | 55 |
| Day 15 — No problems | 179 | 93 | 176 |
| Day 15 — Any problems | 11 | 4 | 26 |
| Day 29 — No problems | 172 | 82 | 171 |
| Day 29 — Any problems | 6 | 3 | 20 |
Participants' self-reported health state within pain/discomfort dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline — No problems | 41 | 15 | 23 |
| Baseline — Any problems | 186 | 99 | 201 |
| Day 8 — No problems | 119 | 59 | 98 |
| Day 8 — Any problems | 99 | 47 | 121 |
| Day 15 — No problems | 152 | 81 | 148 |
| Day 15 — Any problems | 38 | 16 | 54 |
| Day 29 — No problems | 158 | 80 | 157 |
| Day 29 — Any problems | 20 | 5 | 34 |
Participants' self-reported health state within anxiety/depression dimension of five-dimension EuroQol EQ-5D-5L questionnaire. Participants were asked to indicate their health state by selecting the most appropriate response level for them from five ordinal response levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems (5). Results were dichotomized into no problems (level 1) and any problems (levels 2, 3, 4, and 5 combined) for reporting and analysis. Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Baseline — No problems | 78 | 50 | 63 |
| Baseline — Any problems | 149 | 64 | 161 |
| Day 8 — No problems | 121 | 59 | 114 |
| Day 8 — Any problems | 97 | 47 | 105 |
| Day 15 — No problems | 123 | 70 | 119 |
| Day 15 — Any problems | 67 | 27 | 83 |
| Day 29 — No problems | 138 | 65 | 127 |
| Day 29 — Any problems | 40 | 20 | 64 |
Study protocol required reporting of all adverse events (AEs) that (1) led to a change in study treatment regardless of grade, (2) met the serious AE (SAE) or Expedited AE (EAE) reporting requirement, and (3) were Grade 3 or greater. AEs were graded using the DAIDS AE Grading Table (Version 2.1). Severity Grade: 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Life-Threatening, 5 = Death Includes data from follow-up visits occurring through October 23, 2024.
| proportion of participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Proportion of Participants With Grade 3 or Greater Treatment-emergent Adverse Event | 0.044 (0.019 to 0.068) | 0.044 (0.010 to 0.079) | 0.071 (0.040 to 0.102) |
Includes data from follow-up visits occurring through October 23, 2024.
| Participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Number of Participants Who Died From Any Cause | 0 | 0 | 0 |
Plasma tecovirimat concentrations were quantified using validated liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. The lower limit of quantification was 5.0 ng/mL.
No measurements were reported for this outcome.
NIH-required analysis. Subgroup analysis of the primary outcome measure by sex. Interaction of treatment and sex was not tested because of the small number of females enrolled. Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution in the presence of competing events was estimated using the Aalen-Johansen estimator, where all-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
| cumulative proportion of participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Male | 0.83 (0.77 to 0.87) | 0.84 (0.75 to 0.90) | 0.84 (0.78 to 0.88) |
| Female | 1.00 (NA to NA) | 1.00 (NA to NA) | 0.89 (0.22 to 0.99) |
NIH-required analysis. Subgroup analysis of the primary outcome measure by race (White, Non-White). "Non-White" includes participants who identified as Black or African American, Asian, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, "other" race, having more than one race, or having unknown race. Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution in the presence of competing events was estimated using the Aalen-Johansen estimator, where all-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
| cumulative proportion of participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Non-White | 0.83 (0.74 to 0.89) | 0.85 (0.71 to 0.93) | 0.82 (0.72 to 0.88) |
| White | 0.83 (0.74 to 0.89) | 0.83 (0.70 to 0.91) | 0.86 (0.78 to 0.92) |
NIH-required analysis. Subgroup analysis of the primary outcome measure by ethnicity (Hispanic or Latino, Not Hispanic or Latino). Clinical resolution defined as all skin lesions scabbed, desquamated, or healed, and visible mucosal lesions healed. The cumulative proportion with clinical resolution in the presence of competing events was estimated using the Aalen-Johansen estimator, where all-cause death, start of open-label tecovirimat due to disease progression or severe pain, and use of other antivirals with expected activity against mpox were treated as competing events. Follow-up time was censored at last contact. Includes data from follow-up visits occurring through October 23, 2024.
| cumulative proportion of participants | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|
| Hispanic or Latino | 0.85 (0.76 to 0.91) | 0.88 (0.73 to 0.95) | 0.85 (0.76 to 0.91) |
| Not Hispanic or Latino | 0.81 (0.72 to 0.87) | 0.80 (0.67 to 0.88) | 0.83 (0.74 to 0.89) |
Collected over From study entry to study completion at Day 57 or premature study discontinuation.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Tecovirimat (Arm A) | 0/267 (0%) | 4/267 (1.5%) | 7/267 (2.6%) |
| Tecovirimat (Arm A) to Open-Label Tecovirimat (Arm C) | 0/23 (0%) | 2/23 (8.7%) | 12/23 (52.2%) |
| Placebo (Arm B) | 0/132 (0%) | 0/132 (0%) | 4/132 (3%) |
| Placebo (Arm B) to Open-Label Tecovirimat (Arm C) | 0/13 (0%) | 2/13 (15.4%) | 9/13 (69.2%) |
| Open-Label Tecovirimat (Arm C) | 0/281 (0%) | 14/281 (5%) | 14/281 (5%) |
| Event | Tecovirimat (Arm A) | Tecovirimat (Arm A) to Open-Label Tecovirimat (Arm C) | Placebo (Arm B) | Placebo (Arm B) to Open-Label Tecovirimat (Arm C) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|---|---|
| HypersensitivityImmune system disorders | 1/267 | 0/23 | 0/132 | 1/13 | 0/281 |
| Peritonsillar abscessInfections and infestations | 0/267 | 0/23 | 0/132 | 1/13 | 0/281 |
| Skin infectionInfections and infestations | 0/267 | 0/23 | 0/132 | 1/13 | 1/281 |
| MonkeypoxInfections and infestations | 0/267 | 1/23 | 0/132 | 0/13 | 3/281 |
| Rectal abscessInfections and infestations | 1/267 | 1/23 | 0/132 | 0/13 | 1/281 |
| PneumoniaInfections and infestations | 0/267 | 0/23 | 0/132 | 0/13 | 2/281 |
| Haemoglobin decreasedInvestigations | 0/267 | 0/23 | 0/132 | 0/13 | 2/281 |
| LymphadenopathyBlood and lymphatic system disorders | 1/267 | 0/23 | 0/132 | 0/13 | 0/281 |
| Skin ulcerSkin and subcutaneous tissue disorders | 1/267 | 0/23 | 0/132 | 0/13 | 0/281 |
| Abscess limbInfections and infestations | 0/267 | 0/23 | 0/132 | 0/13 | 1/281 |
| Event | Tecovirimat (Arm A) | Tecovirimat (Arm A) to Open-Label Tecovirimat (Arm C) | Placebo (Arm B) | Placebo (Arm B) to Open-Label Tecovirimat (Arm C) | Open-Label Tecovirimat (Arm C) |
|---|---|---|---|---|---|
| MonkeypoxInfections and infestations | 0/267 | 4/23 | 0/132 | 5/13 | 0/281 |
| ProctalgiaGastrointestinal disorders | 0/267 | 4/23 | 0/132 | 2/13 | 0/281 |
| Penile swellingReproductive system and breast disorders | 0/267 | 1/23 | 0/132 | 1/13 | 0/281 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 0/267 | 0/23 | 1/132 | 1/13 | 0/281 |
| LymphadenopathyBlood and lymphatic system disorders | 0/267 | 1/23 | 0/132 | 0/13 | 0/281 |
| SwellingGeneral disorders | 0/267 | 1/23 | 0/132 | 0/13 | 0/281 |
| CellulitisInfections and infestations | 0/267 | 1/23 | 0/132 | 0/13 | 0/281 |
| Penile painReproductive system and breast disorders | 0/267 | 1/23 | 0/132 | 0/13 | 0/281 |
| Pain of skinSkin and subcutaneous tissue disorders | 0/267 | 1/23 | 0/132 | 0/13 | 0/281 |
| Skin ulcerSkin and subcutaneous tissue disorders | 0/267 | 1/23 | 0/132 | 0/13 | 0/281 |
All eligible participants. One participant randomized to the placebo arm was later found ineligible for study participation and excluded from all analyses.
| Age, Continuous(years) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| Median | 34 (28 to 40) | 34 (29 to 41) | 35 (30 to 41) | 34 (28 to 41) |
| Age, Customized(Participants) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| <40 years | 214 | 103 | 194 | 511 |
| >=40 years | 76 | 44 | 87 | 207 |
| Sex/Gender, Customized(Participants) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| Cisgender | 284 | 141 | 269 | 694 |
| Transgender spectrum | 6 | 6 | 12 | 24 |
| Sex: Female, Male(Participants) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| Female | 4 | 5 | 12 | 21 |
| Male | 286 | 142 | 269 | 697 |
| Ethnicity (NIH/OMB)(Participants) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 137 | 60 | 133 | 330 |
| Not Hispanic or Latino | 150 | 82 | 143 | 375 |
| Unknown or Not Reported | 3 | 5 | 5 | 13 |
| Race/Ethnicity, Customized(Participants) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| White | 149 | 86 | 150 | 385 |
| Black or African American | 35 | 11 | 69 | 115 |
| Asian | 19 | 16 | 12 | 47 |
| Native Hawaiian or Other Pacific Islander | 2 | 0 | 1 | 3 |
| American Indian or Alaska Native | 3 | 0 | 1 | 4 |
| Other | 28 | 11 | 15 | 54 |
| Multiple | 6 | 3 | 7 | 16 |
| Unknown | 48 | 20 | 26 | 94 |
| Region of Enrollment(Participants) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| Argentina | 3 | 2 | 3 | 8 |
| United States | 234 | 120 | 241 | 595 |
| Japan | 1 | 1 | 2 | 4 |
| Brazil | 1 | 0 | 13 | 14 |
| Mexico | 13 | 7 | 8 | 28 |
| Thailand | 10 | 4 | 7 | 21 |
| Peru | 28 | 13 | 7 | 48 |
| Days from Symptom Onset, Continuous(days) | Tecovirimat (Arm A) | Placebo (Arm B) | Open-Label Tecovirimat (Arm C) | Total |
|---|---|---|---|---|
| Median | 7 (5 to 10) | 8 (5 to 10) | 8 (6 to 10) | 8 (5 to 10) |
11 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Individual participant data that underlie results in the publication after deidentification
Supporting information: Study protocol, Statistical analysis plan
Time frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH
Access criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. For what types of analyses? To achieve aims in the proposal approved by the ACTG. By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data
Ran from Sep 2022 to primary completion in Oct 2024, 25 months.
Results were first posted in Feb 2026, 1 year 3 months after primary completion.
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Studies of the drug tested here: Tecovirimat
National Institute of Allergy and Infectious Diseases (NIAID) →