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

October 20, 2023 updated by: Calmy Alexandra

A Phase III, Multi-country, Randomized, Placebo-controlled, Double-blinded Trial to Assess the Efficacy and Safety of Tecovirimat Antiviral Treatment for Patients With Monkeypox Virus Disease

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study presented here is the Swiss-Brazil co-sponsored adaptation of the UNITY trial based on the WHO core protocol. It has an original governance to better respond to public health priorities, each country being its own sponsor, allowing for an easier scale-up of the trial and local adaptations of the protocol.

Background and rationale:

Monkeypox is an emerging viral zoonosis caused by a virus of the same name that is closely related to smallpox. It is usually endemic in central and West Africa but since May 2022, the virus has rapidly disseminated to Europe, North and South America, Africa and Australia, and has predominantly affected gay, bisexual and other men who have sex with men (MSM) with multiple partners. On 23 July 2022, the World Health Organization (WHO) declared that the monkeypox outbreak was an international public health emergency. In particular, the WHO called for the use of antivirals for the treatment of monkeypox cases. This declaration must therefore be translated not only into extraordinary public health measures but also as a call for greater investment in research.

This study proposal is a national adaptation for Switzerland and Brazil based on the 'CORE protocol' developed by the WHO. The research team would like to emphasize that this randomized trial is international in scope. Thus, they are joining forces to achieve a more effective and rapid response to important questions, with a harmonized follow-up and in a time frame that can be useful to the patients the medical staff have been caring for since the very beginning of this epidemic. Candidate antivirals are already available for testing in monkeypox. The first studied treatment in this adaptative trial is the antiviral tecovirimat. Tecovirimat (TPOXX®, SIGA Technologies Inc.) is a treatment for smallpox, monkeypox and cowpox. Tecovirimat is approved by the European Medicine Agency (EMA) for this indication for adults and children weighing at least 13 kg, as well as by the United States Food and Drugs Administration (FDA) under expanded access investigational new drug protocol, but it is not yet approved in Switzerland and Brazil.

Objectives:

This study aims to evaluate whether tecovirimat is an efficient and safe antiviral in the treatment of monkeypox in adults and adolescents (14 years old and over).

The primary objective is to evaluate the clinical efficacy of tecovirimat treatment + standard of care (SOC) compared to placebo + SOC for patients with monkeypox as assessed by time to visible lesion(s) resolution. The secondary objectives are to evaluate the clinical efficacy and safety of tecovirimat treatment + SOC compared to placebo + SOC in patients with monkeypox as assessed by mortality, hospitalization, complications, duration of symptoms and virological shedding.

Methods:

This study will include adult and adolescent patients aged ≥14 years with a confirmed or highly suspected monkeypox virus infection and with at least one visible active skin or mucosal lesion. Individuals with a known hypersensitivity to tecovirimat, who are taking medications which cannot be interrupted and for which a major interaction has been described or who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study will not be included. Randomization will be in a ratio of 1:1 to either tecovirimat treatment combined with SOC or to placebo combined with SOC. All participants will be followed-up until day 29 and additionally at day 60 for those who accept this last optional follow-up visit.

Outcome:

The primary outcome is the 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).

Expected results:

The hypothesis is that prompt oral treatment with tecovirimat will result in a reduction of the duration of illness in patients with monkeypox that may correlate with the duration of contagiousness. It is expected that tecovirimat will be well tolerated and acceptable for these patients.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Argentina
      • Ciudad Autonoma de Buenos Aires, Argentina, C1204ABB
        • Not yet recruiting
        • Fundación Huésped
        • Contact:
  • Brazil
      • Belo Horizonte, Brazil
        • Not yet recruiting
        • Faculty of Medicine, Federal University of Minas Gerais
        • Contact:
          • Jorge Andrade Pinto, Dr.
      • Rio De Janeiro, Brazil
        • Not yet recruiting
        • Federal Hospital for State Employees
        • Contact:
          • Esau Custodio João, Dr.
      • Rio De Janeiro, Brazil
        • Not yet recruiting
        • Nova Iguaçu General Hospital
        • Contact:
          • José Henrique Pilotto, Dr.
      • Rio de Janeiro, Brazil
        • Recruiting
        • Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation-FIOCRUZ
        • Contact:
          • Beatriz Grinsztejn, Dr.
      • Salvador, Brazil
        • Not yet recruiting
        • University Hospital Prof. Edgard Santos
        • Contact:
          • Carlos Brites, Dr.
      • São Paulo, Brazil
        • Not yet recruiting
        • Emílio Ribas Institute of Infectious Diseases
        • Contact:
          • Luiz Carlos Pereira Junior, Dr.
      • São Paulo, Brazil
        • Recruiting
        • STD/AIDS Reference and Training Center
        • Contact:
          • José Valdez Ramalho Madruga, Dr.
  • Switzerland
      • Genève, Switzerland, 1211
      • Zürich, Switzerland
    • Vaud
      • Lausanne, Vaud, Switzerland, 1010

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
The control intervention is a placebo and its route of administration will be identical to the experimental intervention administration to allow treatment arm blinding.
Experimental: Tecovirimat
Drug: Tecovirimat

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to all visible lesion(s) resolution
Time Frame: 28 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality within the first 28 days (applied to all patients)
Time Frame: 28 days
All-cause mortality is more reliably measured than monkeypox-specific mortality. It is easy to measure and is reliable.
28 days
All-cause unplanned admission to hospital within first 28 days (applies to outpatients)
Time Frame: 28 days
Most patients will be managed at home or in community and this outcome is an important patient-centered and health system outcome. All-cause is easier to measure than monkeypox specific and will ease data burden.
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)
Time Frame: 28 days
Complications include secondary bacterial skin infection (cellulitis, abscess, necrotizing fasciitis, need for antibiotics), severe pain, ocular impairment (e.g. keratitis), neurologic impairment (e.g. encephalitis) or mental health disturbance, confusion, cardiac impairment (e.g. cardiomyopathy, myocarditis), severe dehydration, and genitourinary complications as urinary retention. Progression to complications is an important patient-centered outcome and an important health system outcome to prepare and anticipate clinical services for monkeypox cases. It is easy to measure, as long as definitions are clear, and the relevant staff is trained. Complications will be differentiated based on drug-related complications and disease-related complications.
28 days
Time to resolution of symptoms and signs within first 28 days (applies to all patients)
Time Frame: 28 days
Symptoms include fatigue, malaise, nausea, vomiting, abdominal pain, anorexia, cough, dysphagia, odynophagia, fever, headache, oral pain, pain with urination, rectal/anal pain. Signs include lymphadenopathy, ocular lesions, pharyngitis, urethritis, and proctitis. Collection of symptoms and signs can be useful to understand the clinical characterization.
28 days
Viral clearance up to 28 days after randomization
Time Frame: 28 days
Occurrence of negative oropharyngeal , rectal swab, and skin swab PCR results, respectively, 7, 14, 21 days and 28 days after randomization. Viral clearance assessment is important to evaluate whether treatment is also a route for reducing transmission.
28 days
Frequency of adverse events (AEs) and serious adverse events (SAEs) for specific therapeutics (applies to all patients)
Time Frame: 60 days
The collection of standardized data of adverse events is of importance in order to increase the understanding of safety and tolerability of the treatment.
60 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Calmy Alexandra

Collaborators

Oswaldo Cruz Foundation
ANRS, Emerging Infectious Diseases

Investigators

  • Study Director: Yazdan Yazdapanah, Pr., ANRS, Emerging Infectious Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 3, 2023

Primary Completion (Estimated)

January 1, 2024

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

October 27, 2022

First Submitted That Met QC Criteria

October 27, 2022

First Posted (Actual)

October 28, 2022

Study Record Updates

Last Update Posted (Actual)

October 23, 2023

Last Update Submitted That Met QC Criteria

October 20, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-01579

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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