STOMP: Study of Tecovirimat for Human Monkeypox Virus

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT05534984

Collaborator

SIGA Technologist (Other)

530

Enrollment

Locations

Arms

12.6

Anticipated Duration (Months)

8.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Monkeypox	Drug: Tecovirimat Oral Capsule Drug: Placebo Drug: Tecovirimat Oral Capsule (Open Label)	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

530 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Monkeypox Virus Disease

Actual Study Start Date :

Sep 12, 2022

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A	Drug: Tecovirimat Oral Capsule Drug: Tecovirimat Oral capsules 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
Placebo Comparator: Arm B	Drug: Placebo Drug: Placebo Oral capsules 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
Experimental: Arm C	Drug: Tecovirimat Oral Capsule (Open Label) Participants weighing 4 to <6kg and >7 days old - Tecovirimat 50mg every 12 hours for 14 days Participants weighing 2.5 to <4kg and >7 days to <4 weeks old - Tecovirimat 20 mg every 12 hours for 14 days Participants weighing 4 to <6kg and ≤7 days old - Tecovirimat 50mg every 24 hours for 14 days Participants weighing 2.5 to <4 kg and ≤7 days old - Tecovirimat 20mg every 24 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 (2 capsules) 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

Arm

Intervention/Treatment

Experimental: Arm A

Drug: Tecovirimat Oral Capsule

Drug: Tecovirimat Oral capsules 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

Placebo Comparator: Arm B

Drug: Placebo

Drug: Placebo Oral capsules 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

Experimental: Arm C

Drug: Tecovirimat Oral Capsule (Open Label)

Participants weighing 4 to <6kg and >7 days old - Tecovirimat 50mg every 12 hours for 14 days Participants weighing 2.5 to <4kg and >7 days to <4 weeks old - Tecovirimat 20 mg every 12 hours for 14 days Participants weighing 4 to <6kg and ≤7 days old - Tecovirimat 50mg every 24 hours for 14 days Participants weighing 2.5 to <4 kg and ≤7 days old - Tecovirimat 20mg every 24 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 (2 capsules) 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

Outcome Measures

Primary Outcome Measures

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 [Up to day 29]

Secondary Outcome Measures

Pain assessed by 11-point numerical rating scale for pain [Through day 29]
Time to development of severe HMPXV in those without severe HMPXV at baseline [Through day 57]
Level of HMPXV in blood [Through day 57]
Level of HMPXV in skin lesions [Through day 57]
Level of HMPXV in oropharynx [Through day 57]
Level of HMPXV in rectum [Through day 57]
Level of HMPXV in genital secretions [Through day 57]
Time to complete lesion healing defined as all lesions being re-epithelialized [Up to day 29]
Participant-reported adherence [Through day 15]
Participant-reported quality-of-life as measured by EQ-5D-5L [Through day 29]
Occurrence of Grade 3 or greater adverse event [Through day 57]
All-cause mortality [Through day 57]
Tecovirimat concentrations in blood in children less than 18 years of age [Through day 15]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Laboratory-confirmed or presumptive HMPXV infection.
HMPXV illness of <14 days duration immediately prior to study entry.
At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis with or without visible ulcers.
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:

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:

Participants age <18 years at the time of study entry
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):

Prior or concomitant receipt of tecovirimat (e.g., under an alternative access mechanism.
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.
Participants who, in the judgement of the investigator, will be at significantly increased risk as a result of participation in the study.
Participants who require intravenous dosing of tecovirimat.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama CRS	Birmingham	Alabama	United States	35294
2	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
3	Los Angeles LGBT Center CRS	Los Angeles	California	United States	90028
4	Usc La Nichd Crs	Los Angeles	California	United States	90033
5	UCLA CARE Center CRS	Los Angeles	California	United States	90035
6	David Geffen School of Medicine at UCLA NICHD CRS	Los Angeles	California	United States	90095
7	Easy Bay AIDS Center CRS City: Oakland	Oakland	California	United States	94609
8	Stanford AIDS Clinical Trials Unit CRS	Palo Alto	California	United States	94304
9	UCSD Antiviral Research Center CRS	San Diego	California	United States	92103
10	University of California, San Francisco HIV/AIDS CRS	San Francisco	California	United States	94110
11	Harbor University of California Los Angeles Center	Torrance	California	United States	90502
12	University of Colorado Denver NICHD CRS	Aurora	Colorado	United States	80045
13	University of Colorado Hospital CRS	Aurora	Colorado	United States	80045
14	Denver Public Health CRS	Denver	Colorado	United States	80204
15	Yale University School of Medicine	New Haven	Connecticut	United States	06510
16	Malcom Randall VA Medical Center CRS	Gainesville	Florida	United States	32610
17	University of Florida Jacksonville NICHD CRS	Jacksonville	Florida	United States	32209
18	University of Miami / Jackson Memorial Hospital	Miami	Florida	United States	33136
19	University of Miami/Pediatric Perinatal HIV NICHD CRS	Miami	Florida	United States	33136
20	Orlando Immunology Center CRS	Orlando	Florida	United States	32803
21	Univ. of South Florida (USF) College of Medicine A	Tampa	Florida	United States	33606
22	The Ponce de Leon Center CRS	Atlanta	Georgia	United States	30308
23	Emory University School of Medicine NICHD CRS	Atlanta	Georgia	United States	30322
24	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
25	Northwestern University	Chicago	Illinois	United States	60611
26	Rush University Cook County Hospital Chicago NICHD CRS	Chicago	Illinois	United States	60612
27	Rush University CRS	Chicago	Illinois	United States	60612
28	Johns Hopkins University CRS	Baltimore	Maryland	United States	21205
29	Massachusetts General Hospital CRS (MGH CRS)	Boston	Massachusetts	United States	02114
30	Brigham and Women's Hospital Therapeutics	Boston	Massachusetts	United States	02115
31	Henry Ford Hospital CRS	Detroit	Michigan	United States	48202
32	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
33	Washington University Therapeutics (WT) CRS	Saint Louis	Missouri	United States	63110
34	University of Nebraska Medical Center (Specialty Care Center)	Omaha	Nebraska	United States	68198
35	New Jersey Medical School Clinical Research Center	Newark	New Jersey	United States	07103
36	Jacobi Medical Center Bronx NICHD CRS	Bronx	New York	United States	10461
37	Mount Sinai West Samuels CRS	New York	New York	United States	10019
38	Harlem Prevention Center	New York	New York	United States	10027
39	Columbia Physicians & Surgeons (P&S) CRS	New York	New York	United States	10032
40	New York Blood Center	New York	New York	United States	10065
41	Weill Cornell Chelsea CRS	New York	New York	United States	10065
42	Weill Cornell Uptown CRS	New York	New York	United States	10065
43	Bronx-Lebanon Hospital Center NICHD CRS	New York	New York	United States	10457
44	Infectious Disease Clinical and Translational Research	New York	New York	United States	11029
45	University of Rochester Adult HIV Therapeutic	Rochester	New York	United States	14642
46	SUNY Stony Brook NICHD CRS	Stony Brook	New York	United States	11794
47	Duke University Medical Center CRS	Durham	North Carolina	United States	27710
48	Wake Forest Baptist Medical Center CRS	Winston-Salem	North Carolina	United States	27157
49	Cincinnati CRS	Cincinnati	Ohio	United States	45267
50	Case Western Reserve University CTU	Cleveland	Ohio	United States	44106
51	Ohio State University CRS	Columbus	Ohio	United States	43210
52	Penn Therapeutics CRS	Philadelphia	Pennsylvania	United States	19104
53	University of Pittsburgh CRS	Pittsburgh	Pennsylvania	United States	15213
54	St. Jude Children's Research Hospital ATN CRS	Memphis	Tennessee	United States	38105
55	Vanderbilt Therapeutics CRS	Nashville	Tennessee	United States	37204
56	North Texas Infectious Disease Consultants	Dallas	Texas	United States	75246
57	UT Southwestern Infectious Disease Research Unit	Dallas	Texas	United States	75390
58	Baylor College of Medicine / Texas Children's Hospital NICHD CRS	Houston	Texas	United States	77030
59	Houston AIDS Research Team (HART) CRS	Houston	Texas	United States	77030
60	University of Texas, San Antonio	San Antonio	Texas	United States	78229
61	University of Washington Positive Research	Seattle	Washington	United States	98104
62	IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS	San Juan		Puerto Rico	00935

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
SIGA Technologist

Investigators

Study Chair: Timothy Wilkin, MD, MPH, Cornell

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT05534984

Other Study ID Numbers:

A5418
38982

First Posted:

Sep 10, 2022

Last Update Posted:

Sep 13, 2022

Last Verified:

Sep 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)

HMPXV

Additional relevant MeSH terms:

Monkeypox

Study Results

No Results Posted as of Sep 13, 2022