Tecovirimat for Treatment of Monkeypox Virus

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

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.

Study Overview

• Status: Completed
• Conditions: Monkeypox
• Intervention / Treatment: Drug: Tecovirimat Oral Capsule; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 597
• Phase: Phase 2

Contacts and Locations

Study Locations

• Democratic Republic of the Congo
  • Kole, Democratic Republic of the Congo
    • L'Hôpital Général de Référence de Kole
  • Tunda, Democratic Republic of the Congo
    • L'Hôpital Général de Référence de Tunda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tecovirimat; Tecovirimat capsules administered orally to participants for 14 days plus SOC.	Drug: Tecovirimat Oral Capsule; 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); Other Names: TPOXX
Placebo Comparator: Placebo; Matching placebo capsules administered orally to participants for 14 days plus SOC.	Drug: Placebo; Capsules to match tecovirimat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to day 28
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.	up to day 28
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	day 14
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	day 14
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	day 14
Mortality Within the First 28 Days Post-randomization	Number of deaths post-randomization	up to day 28
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)	Up to day 14
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)	Up to day 14
Incidence of Adverse Events	Number of participants with an adverse event up to day 28	up to day 28
Incidence of Bacterial Infection Adverse Events	Number of participants with a bacterial infection adverse event up to day 28	up to day 28

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Institut National de Recherche Biomédicale. Kinshasa, République Démocratique du Congo
• Investigators: Principal Investigator: Jean-Jacques Muyembe-Tamfum, MD PhD, Kinshasa University

Publications and helpful links

General Publications

• PALM007 Writing Group; Ali R, Alonga J, Biampata JL, Kombozi Basika M, Maljkovic Berry I, Bisento N, Blum E, Bonnett T, Cone K, Crozier I, Davey R, Dilu A, Dodd LE, Gulati I, Hruby D, Ibanda A, Isse F, Kasareka SS, Kayembe G, Kojan R, Luzolo EK, Lane HC, Lawanga L, Liesenborghs L, Shosongo Lunghe C, Lula Y, Lusakibanza M, Lutete GT, Mbala-Kingebeni P, Miranda A, Mukadi-Bamuleka D, Mukendi G, Lupola PM, Muyembe-Tamfum JJ, Ndungunu R, Nganga B, Ntamabyaliro N, Nussenblatt V, Omulepu I, Omalokoho Onosomba J, Proschan M, Rubenstein K, Saknite I, Schechner A, Shaw-Saliba K, Sivahera B, Smolskis M, Tillman A, Tkaczyk E, Tshimanga C, Tshiani Mbaya O, Tshomba A, Yemba Unda Tshomba F, Vallee D, Vogel S, Weyers S. Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo. N Engl J Med. 2025 Apr 17;392(15):1484-1496. doi: 10.1056/NEJMoa2412439.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2022
• Primary Completion (Actual): September 3, 2024
• Study Completion (Actual): September 3, 2024

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Monkeypox; MPXV
• Additional Relevant MeSH Terms: Infections; Virus Diseases; Poxviridae Infections; DNA Virus Infections; Animal Diseases; Primate Diseases; Rodent Diseases; Mpox, Monkeypox; Anti-Infective Agents; Antiviral Agents; tecovirimat
• Other Study ID Numbers: PALM 007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes