Assessment of the Efficacy and Safety of Tecovirimat in Patients With Monkeypox Virus Disease

NCT05597735 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2022-01579
• Study Type: interventional
• Target: 480
• Locations: 3 countries
• Sites: 12

Brief Summary

The overall purpose of this study is to evaluate whether tecovirimat is an efficient and safe antiviral in the treatment of monkeypox in adults and adolescents (14 years old and older). The primary objective is to evaluate the clinical efficacy, as assessed by time to all visible lesion(s) resolution, of tecovirimat treatment + Standard of Care (SOC) compared to placebo + SOC for patients with monkeypox. The secondary objective is to evaluate the clinical efficacy, as assessed by mortality, hospitalization, complications, duration of symptoms and virological shedding, and the safety of tecovirimat treatment + SOC compared to placebo + SOC in patients with monkeypox.

Conditions

Monkeypox; Mpox

Keywords

Tecovirimat; Antiviral agent

Outcome Measures

Primary Outcomes (1)

• Time to all visible lesion(s) resolution

  Time for all visible lesions (skin, mucosal) to heal with a new fresh layer of skin re-epithelialization (i.e resurfacing of a wound with a new epithelium layer). For skin lesions, typically this means the lesion has scabbed, desquamated and new layer of skin has been formed. For mucosal lesions, the phase of scabbing and desquamation is absent, and healing with new layer of skin ensues.

  28 days

Secondary Outcomes (6)

• All-cause mortality within the first 28 days (applied to all patients)

  28 days

• All-cause unplanned admission to hospital within first 28 days (applies to outpatients)

  28 days

• Occurrence of patients with a complication within first 28 days (applies to all patients who did not already have a complication at baseline)

  28 days

• Time to resolution of symptoms and signs within first 28 days (applies to all patients)

  28 days

• Viral clearance up to 28 days after randomization

  28 days

Study Arms (2)

Tecovirimat

EXPERIMENTAL

Drug: Tecovirimat

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tecovirimat DRUG

The experimental intervention is tecovirimat, available as immediate-release capsules containing tecovirimat monohydrate, equivalent to 200 mg of tecovirimat. The route of administration of tecovirimat is oral. Tecovirimat treatment will be initiated as soon as possible after diagnosis. The international recommended doses will be followed: * 25 kg to less than 40 kg: 400 mg (two tecovirimat 200 mg capsules) every 12 hours for 14 consecutive days. * 40 kg and above: 600 mg (three tecovirimat 200 mg capsules) every 12 hours for 14 consecutive days.

Tecovirimat

Placebo DRUG

The control intervention is a placebo and its route of administration will be identical to the experimental intervention administration to allow treatment arm blinding.

Placebo

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults and adolescents (14 years old and older) with laboratory-confirmed (PCR if available) or highly suspected monkeypox virus infection of any duration
• At least one visible active skin or mucosal lesion
• Reachable via smartphone (for video calls) for outpatient participants
• Signed informed consent

You may not qualify if:

• Current or planned use of another investigational drug at any point during study participation.
• Ongoing treatment which cannot be interrupted and for which a major interaction has been described with tecovirimat
• Patients who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study (for example: if the investigator judges that an antiviral treatment is indicated in the framework of compassionate therapeutic access in Switzerland).
• Hypersensitivity to tecovirimat

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• University Hospital, Geneva: collaborator
• Oswaldo Cruz Foundation: collaborator
• Fundacion Huesped, Buenos Aires, Argentina: collaborator

Study Sites (12)

Fundación Huésped

Buenos Aires, C1204ABB, Argentina

RECRUITING

Faculty of Medicine, Federal University of Minas Gerais

Belo Horizonte, Brazil

RECRUITING

Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation-FIOCRUZ

Rio de Janeiro, Brazil

RECRUITING

Federal Hospital for State Employees

Rio de Janeiro, Brazil

RECRUITING

Nova Iguaçu General Hospital

Rio de Janeiro, Brazil

RECRUITING

University Hospital Prof. Edgard Santos

Salvador, Brazil

NOT YET RECRUITING

Emílio Ribas Institute of Infectious Diseases

São Paulo, Brazil

NOT YET RECRUITING

STD/AIDS Reference and Training Center

São Paulo, Brazil

RECRUITING

Hôpitaux Universitaires de Genève

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

Pr Alexandra Calmy

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

CHUV

Lausanne, Canton of Vaud, 1010, Switzerland

NOT YET RECRUITING

Zürich checkpoint

Zurich, Canton of Zurich, Switzerland

RECRUITING

Related Publications (9)

• Thornhill JP, Barkati S, Walmsley S, Rockstroh J, Antinori A, Harrison LB, Palich R, Nori A, Reeves I, Habibi MS, Apea V, Boesecke C, Vandekerckhove L, Yakubovsky M, Sendagorta E, Blanco JL, Florence E, Moschese D, Maltez FM, Goorhuis A, Pourcher V, Migaud P, Noe S, Pintado C, Maggi F, Hansen AE, Hoffmann C, Lezama JI, Mussini C, Cattelan A, Makofane K, Tan D, Nozza S, Nemeth J, Klein MB, Orkin CM; SHARE-net Clinical Group. Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022. N Engl J Med. 2022 Aug 25;387(8):679-691. doi: 10.1056/NEJMoa2207323. Epub 2022 Jul 21.

  PMID: 35866746 BACKGROUND

• Girometti N, Byrne R, Bracchi M, Heskin J, McOwan A, Tittle V, Gedela K, Scott C, Patel S, Gohil J, Nugent D, Suchak T, Dickinson M, Feeney M, Mora-Peris B, Stegmann K, Plaha K, Davies G, Moore LSP, Mughal N, Asboe D, Boffito M, Jones R, Whitlock G. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect Dis. 2022 Sep;22(9):1321-1328. doi: 10.1016/S1473-3099(22)00411-X. Epub 2022 Jul 1.

  PMID: 35785793 BACKGROUND

• Siegrist EA, Sassine J. Antivirals With Activity Against Mpox: A Clinically Oriented Review. Clin Infect Dis. 2023 Jan 6;76(1):155-164. doi: 10.1093/cid/ciac622.

  PMID: 35904001 BACKGROUND

• Smith SK, Self J, Weiss S, Carroll D, Braden Z, Regnery RL, Davidson W, Jordan R, Hruby DE, Damon IK. Effective antiviral treatment of systemic orthopoxvirus disease: ST-246 treatment of prairie dogs infected with monkeypox virus. J Virol. 2011 Sep;85(17):9176-87. doi: 10.1128/JVI.02173-10. Epub 2011 Jun 22.

  PMID: 21697474 BACKGROUND

• O'Laughlin K, Tobolowsky FA, Elmor R, Overton R, O'Connor SM, Damon IK, Petersen BW, Rao AK, Chatham-Stephens K, Yu P, Yu Y; CDC Monkeypox Tecovirimat Data Abstraction Team. Clinical Use of Tecovirimat (Tpoxx) for Treatment of Monkeypox Under an Investigational New Drug Protocol - United States, May-August 2022. MMWR Morb Mortal Wkly Rep. 2022 Sep 16;71(37):1190-1195. doi: 10.15585/mmwr.mm7137e1.

  PMID: 36107794 BACKGROUND

• Desai AN, Thompson GR 3rd, Neumeister SM, Arutyunova AM, Trigg K, Cohen SH. Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection. JAMA. 2022 Oct 4;328(13):1348-1350. doi: 10.1001/jama.2022.15336.

  PMID: 35994281 BACKGROUND

• Adler H, Gould S, Hine P, Snell LB, Wong W, Houlihan CF, Osborne JC, Rampling T, Beadsworth MB, Duncan CJ, Dunning J, Fletcher TE, Hunter ER, Jacobs M, Khoo SH, Newsholme W, Porter D, Porter RJ, Ratcliffe L, Schmid ML, Semple MG, Tunbridge AJ, Wingfield T, Price NM; NHS England High Consequence Infectious Diseases (Airborne) Network. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022 Aug;22(8):1153-1162. doi: 10.1016/S1473-3099(22)00228-6. Epub 2022 May 24.

  PMID: 35623380 BACKGROUND

• Carvalho T. The unknown efficacy of tecovirimat against monkeypox. Nat Med. 2022 Nov;28(11):2224-2225. doi: 10.1038/d41591-022-00094-0. No abstract available.

  PMID: 36100750 BACKGROUND

• Merchlinsky M, Albright A, Olson V, Schiltz H, Merkeley T, Hughes C, Petersen B, Challberg M. The development and approval of tecoviromat (TPOXX(R)), the first antiviral against smallpox. Antiviral Res. 2019 Aug;168:168-174. doi: 10.1016/j.antiviral.2019.06.005. Epub 2019 Jun 7.

  PMID: 31181284 BACKGROUND

Related Links

• WHO Director-General's statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox - 23 July 2022
• Second meeting of the International Health Regulations (2005) (IHR) Emergency Committee regarding the multi-country outbreak of monkeypox
• CORE PROTOCOL - An international adaptive multi-country randomized,placebo-controlled, double-blinded trial of the safety and efficacy of treatments for patients with monkeypox virus disease

MeSH Terms

Conditions

Mpox, Monkeypox

Interventions

tecovirimat

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Study Officials

• Yazdan Yazdapanah, Pr.

  ANRS, Emerging Infectious Diseases

  STUDY DIRECTOR

Central Study Contacts

Michele GENIN, PhD

CONTACT

0182533538; michele.genin@inserm.fr

Alexandra Calmy, Pr

CONTACT

0223729812; alexandra.calmyl@hcuge.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Randomized, Placebo-controlled, Double-blinded Trial

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: October 28, 2022
• Study Start: March 3, 2023
• Primary Completion: September 30, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 15, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (7); CH (4); AR (1)