Clinical trial NCT05534984: Study of Tecovirimat for Human Mpox Virus
Official title: A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Mpox Virus Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: MPOX
Keywords: HMPXV
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: SIGA Technologies
First posted: 2022-09-10
Enrollment: 719
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A5418 is a randomized, placebo-controlled, double-blind study to establish the efficacy of tecovirimat for the treatment of people with laboratory-confirmed or presumptive HMPXV disease.

Detailed description: Eligible and consented participants for the randomized arms (N=530) will be randomized 2:1 to receive either tecovirimat or placebo; participants with severe disease, significant skin conditions, participants with severe immune suppression will receive open-label tecovirimat. Participants who are pregnant or breastfeeding will receive open-label tecovirimat after discussion of the potential risks and benefits. Participants less than 18 years of age will receive open-label tecovirimat. Participants receiving a potent inducing concomitant medication will receive open-label tecovirimat.

Once enrolled, study drug administration will be for 14 days. Participants who progress to severe HMPXV disease will be seen in person for a confirmation of progression. If severe disease is confirmed, participants will stop blinded study treatment and start a 14-day course of open-label tecovirimat. Participants reporting severe pain 5 days after randomization will stop blinded study treatment and start a 14-day course of open-label tecovirimat.

Participants will self-monitor skin and/or mucosal lesions daily through 29 days or resolution (whichever comes first), complete a daily diary of symptoms and complete a daily numerical rating scale for pain assessment.

Participants will be seen weekly through day 29 for assessment of HMPXV disease, safety assessments, HMPXV sampling similar to that described for entry, and swabbing of new HMPXV lesions.

Participants will be seen at day 57 to assess for possible recrudescence of infection (i.e., new lesions occurring after initial resolution of disease.

Eligibility criteria: Inclusion Criteria (All participants; Arms A, B, and C):

1. Laboratory-confirmed or presumptive HMPXV infection.
2. HMPXV illness of \<14 days duration immediately prior to study entry.
3. At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers.
4. Non-pregnant people of reproductive potential must agree to use at least one 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.

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:

1. Participants age \<18 years at the time of study entry
2. Those with severe HMPXV disease

Those with or without severe disease and with one or more of the following will also be enrolled into Arm C:

* Severe immunosuppression
* Skin conditions placing the person at higher risk for disseminated infection

Exclusion Criteria (All participants; Arms A, B, and C):

1. Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism.
2. Planned initiation of intramuscular cabotegravir/rilpivirine during study drug administration or for two weeks following completion of study drug administration. Participants who are stable on long-acting intramuscular cabotegravir/rilpivirine may enroll.
3. Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study.
4. Participants who require intravenous dosing of tecovirimat.

Primary outcomes:
measure: Time to clinical resolution, defined as the first day on which all skin lesions are scabbed, desquamated or healed, and visible mucosal lesions are healed
timeFrame: Up to day 29
Secondary outcomes:
measure: Pain assessed by 11-point numerical rating scale for pain
timeFrame: Through day 29
measure: Time to development of severe HMPXV in those without severe HMPXV at baseline
timeFrame: Through day 57
measure: Level of HMPXV in blood
timeFrame: Through day 57
measure: Level of HMPXV in skin lesions
timeFrame: Through day 57
measure: Level of HMPXV in oropharynx
timeFrame: Through day 57
measure: Level of HMPXV in rectum
timeFrame: Through day 57
measure: Level of HMPXV in genital secretions
timeFrame: Through day 57
measure: Time to complete lesion healing defined as all lesions being re-epithelialized
timeFrame: Up to day 29
measure: Participant-reported adherence
timeFrame: Through day 15
measure: Participant-reported quality-of-life as measured by EQ-5D-5L
timeFrame: Through day 29
measure: Occurrence of Grade 3 or greater adverse event
timeFrame: Through day 57
measure: All-cause mortality
timeFrame: Through day 57
measure: Tecovirimat concentrations in blood in children less than 18 years of age
timeFrame: Through day 15
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama CRS
state: Alabama
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles LGBT Center CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Sacramento
country: United States
facility: University of California, Davis CRS
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco HIV/AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor University of California Los Angeles Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver NICHD CRS
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Denver
country: United States
facility: Denver Public Health CRS
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: University of Miami / Jackson Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Univ. of South Florida (USF) College of Medicine A
state: Florida
city: Atlanta
country: United States
facility: The Ponce de Leon Center CRS
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Cook County Hospital Chicago NICHD CRS
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital CRS (MGH CRS)
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital Therapeutics
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital CRS
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Chelsea CRS
state: New York
city: New York
country: United States
facility: Mount Sinai West Samuels CRS
state: New York
city: New York
country: United States
facility: Harlem Prevention Center
state: New York
city: New York
country: United States
facility: Columbia Physicians & Surgeons (P&S) CRS
state: New York
city: New York
country: United States
facility: Weill Cornell Uptown CRS
state: New York
city: New York
country: United States
facility: Bronx-Lebanon Hospital Center NICHD CRS
state: New York
city: New York
country: United States
facility: Infectious Disease Clinical and Translational Research
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Durham
country: United States
facility: Duke University Medical Center CRS
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University CTU
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Philadelphia
country: United States
facility: Penn Therapeutics CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh CRS
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital ATN CRS
state: Tennessee
city: Dallas
country: United States
facility: North Texas Infectious Disease Consultants
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Infectious Disease Research Unit
state: Texas
city: Houston
country: United States
facility: Houston AIDS Research Team (HART) CRS
state: Texas
city: San Antonio
country: United States
facility: University of Texas, San Antonio
state: Texas
city: Seattle
country: United States
facility: University of Washington Positive Research
state: Washington
city: Buenos Aires
country: Argentina
facility: Fundacion Huesped CRS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao CRS
city: São Paulo
country: Brazil
facility: Centro de Pesquisas Clínicas IC-HCFMUSP CRS
city: Tokyo
country: Japan
facility: National Center for Global Health and Medicine
city: Mexico City
country: Mexico
facility: Nutricion Mexico CRS
city: Callao
country: Peru
facility: Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) CRS
city: Lima
country: Peru
facility: Barranco CRS
city: Lima
country: Peru
facility: San Miguel CRS
city: Lima
country: Peru
facility: Socios En Salud Sucursal Peru
city: Lima
country: Peru
facility: Via Libre CRS
city: Johannesburg
country: South Africa
facility: Soweto CRS
city: Johannesburg
country: South Africa
facility: University of the Witwatersrand Helen Joseph (WITS HJH)
city: Bangkok
country: Thailand
facility: Thai Red Cross AIDS Research Centre
city: Bangkok
country: Thailand
facility: Vaccine Trial Centre, Mahidol University CRS
Study officials:
affiliation: Cornell
name: Timothy Wilkin, MD, MPH
role: STUDY_CHAIR
References: