臨床研究等提出・公開システム

A multicenter, open-label, double-arm trial to evaluate the efficacy and safety of oral tecovirimat therapy for patients with mpox or smallpox.

A multicenter, open-label, double-arm trial to evaluate the efficacy and safety of oral tecovirimat therapy for patients with mpox or smallpox.

31

This study evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into the treatment (oral tecovirimat) group and the control group. No randomization was performed. Participants voluntarily chose the group they wished to join. All 31 subjects were male, aged 21 to 74 years (mean age:39 years). Nineteen subjects had HIV infection. Among them, three patients had risk factors for severe disease, and their CD4-positive T lymphocyte counts were below 200.

All 31 registered cases selected the treatment group, with 2 cases receiving multiple courses of tecovirimat. While 7 cases withdrew consent, none of the research subjects refused the use of samples or information after consent withdrawal.

Adverse events following trial inclusion occurred in only 2 of 31 cases. One case was non-serious, while the other involved serious symptoms (multiple organ failure). Both cases were assessed as having no causal relationship.

The total number of registered cases throughout the entire study period was 31, all of which were included in the Full Analysis Set (FAS). There were no major non-compliant cases or discontinuations, and the FAS and Per Protocol Set (PPS) were identical. All registered cases were assigned to the tecovirimat administration group. The safety analysis population was also identical to the FAS and PPS. Primary Endpoint The proportion of patients with a Ct value of 40 or higher in the PCR test of skin samples from the rash site 14 days after study entry was 16 of 23 (69.6%). In this study, 23 of the 31 patients included in the FAS were evaluable. As all cases were in the tecovirimat group, comparative analysis with a control group was not feasible. Therefore, reporting is limited to descriptive epidemiology. This approach will be applied to all items as a general rule. Secondary Endpoints The mortality rate at 14 and 30 days after study enrollment was 0 of 31 cases (0%) for both time points. Viral loads in blood, throat swab, skin lesion, and urine at 14, 21, 30, 60, and 120 days after study enrollment were as follows: Blood 14 days: ND (24, 381) 21 days: ND (18, ND) 30 days: ND (18, 91) 60 days: ND (14, 59) 120 days: ND (11, ND) Throat Swab 14 days: ND (24, 229) 21 days: ND (18, 1038) 30 days: ND (18, 88) 60 days: ND (14, 39.82) 120 days: ND (11, ND) Skin Lesion 14 days: ND (23, 5829167) 21 days: ND (11, 126) 30 days: ND (4, 122) 60 days: ND (2, ND) 120 days: ND (1, ND) Urine 14 days: ND (24, 942) 21 days: ND (18, 247) 30 days: ND (18, ND) 60 days: ND (14, 122) 120 days: ND (11, ND) Values are medians. Units are copies/ml. Numbers in parentheses indicate (number of evaluable cases, maximum value). The minimum value is always ND (Not Detected) and is therefore omitted. For convenience, ND was treated as 0 copies/ml when calculating the median. Viral load in semen at 60 and 120 days after study enrollment was evaluated in 11 and 10 cases, respectively. No cases showed detectable virus. Regarding the duration of persistent fever of 37.5 degrees Celsius or higher after study enrollment, fever was observed in 9 of 31 cases. In 4 cases, fever lasted only 1 day; in 2 cases, it lasted 2 days. In the remaining 3 cases, fever persisted for 3 days, 9 days, and 42 days, respectively. Adverse events after study enrollment were observed in 2 of 31 cases. One case was non serious, while the other included serious symptoms (multiple organ failure). Both cases were assessed as having no causal relationship. General condition (assessed in three stages: total bedridden, partial bedridden, or total ambulation) was evaluated at study entry, 14 days, and 30 days after entry. At 14 days, 28 of 31 cases were assessed: 26 were total ambulation and 2 were total bedridden. At 30 days, 21 of 31 cases were evaluated: 20 were total ambulation and 1 remained total bedridden.

All 31 enrolled cases selected the tecovirimat group, with 2 cases receiving multiple courses of tecovirimat. Regarding the proportion of patients with a Ct value 40 or higher in PCR testing of skin samples from the rash site 14 days after study enrollment, 16 of 23 evaluable cases (69.6%) achieved this. The mortality rate at 14 and 30 days after study enrollment was 0 out of 31 cases (0%) for both time points.

Oct. 31, 2025

No

No plans at this time.

https://jrct.mhlw.go.jp/latest-detail/jRCTs031220169

Morioka Shinichiro

Japan Institute for Health Security (JIHS)

1-21-1 Toyama Shinjyuku-ku Tokyo

morioka.sh@jihs.go.jp

Saito Sho

Japan Institute for Health Security (JIHS)

1-21-1 Toyama Shinjyuku-ku Tokyo

+81-3-3202-7181

saito.s@jihs.go.jp

Complete

June. 28, 2022

Interventional

non-randomized controlled trial

open(masking not used)

no treatment control/standard of care control

parallel assignment

treatment purpose

1) Patients who can provide written consent for participation in the study.
2) Male or female patients whose weight is 13kg or more.
3)Patients who are diagnosed with mpox or smallpox.However, smallpox is diagnosed when the pathogen is detected in a blister, pustule, crust,pharyngeal swab, or blood specimen, etc., and Mpox is diagnosed when the pathogen is detected in a skin or mucosal lesion, blister contents, nasopharyngeal swab, pharyngeal swab, anorectal swab, other mucosal swab, blood, urine, or other materials suitable for the test method, by the following methods. The diagnosis is made when pathogens are detected in pharyngeal swab fluid, anorectal swab fluid, other mucous membrane swab fluid, blood, urine, or other materials suitable for the test metho
d by the following methods
-Direct observation of virus particles by electron microscopy
-Detection of pathogens by isolation and identification
-Detection of pathogen antigens by fluorescent antibody method
-Detection of pathogen genes by PCR method
4)Patients who agree to be hospitalised until the first Tecovirimat course of oral treatment is completed, if oral
Tecovirimat is administerd.
5) Patients with severe mpox or mpox with high risk of severe disease
All of 1)-3) must be met. As for mpox patients, 4) and 5) also must be met.

1) Patients who have experienced any anaphylactic reaction to oral Tecovirimat or its ingredients.
2)Patients whom the study doctor considered to be ineligible.

Note 1) breast-feeding females will be counseled that tecovirimat has not been studied in breast-feeding women and may opt to cease breast-feedingfor the duration of the treatment and at least 30 days after the last dose of drug and thus be eligible for the treatment arm. Women who choose to continue breast-feeding will not be enrolled in the treatment arm.

Note 2) Although reproductive toxicity has not been adequately evaluated in animal studies, no cle
ar reproductive toxicity has been demonstrated to date. However, due to the lack of actual experience with administration to pregnant human women, the drug's package insert states that administration of Tecovilimat during pregnancy is not recommended. However, because there are no other candidates for effective treatment against mpox or smallpox, and because mpox can be transmitted transplacental to the fetus, causing miscarriage, premature delivery, or stillbirth, pregnant individuals should be fully aware of the above advantages and disadvantages of tecovirimat administration before they are eligible to participate as a dosing group The pregnant woman must fully understand the advantages and disadvantages of Tecovilimat administration described above to be eligible to participate in the study.

Note 3) In the case that a patient in the non-treatment arm wishes to join the treatment arm, the patient will be allowed to do so if the study doctor judges appropriate, after withdrawing the consent and providing another written consent.

Both

Mpox, Smallpox

Tecovirimat Arm (Treatment arm): Tecovirimat will be administered as follows:
Body weight
For those whose body weight is 13 kg or more - less than 25 kg: 200 mg should be taken orally every 12 hours after meals In the morning and evening for14 days.
For those whose body weight is 25kg or more - less than 40kg: 400 mg should be taken orally every 12 hours after meals In the morning and evening for 14 days.
For those whose body weight is 40kg or more: 600mg should be taken orally every 12 hours after meals In the morning and evening for 14 days.
It is permissible to administer more than two courses (one course: 14 days) of Tecovirimat if deemed necessary by the principal investigator.

Mpox, Smallpox

Ratio of the patients whose Ct value of PCR testingusing specimens from rash lesions equals or exceeds 40 after 14 days of study inclusion.

-Mortality rate 14 and 30 days after the participation of the study.
-Viral load in blood, pharyngeal swabs, skin and urine sample 14, 21, 30, 60 and 120 days after the participation of the study.
However, when multiple courses of Tecovirimat are administered, virus levels in blood, throat wipes, skin, and urine are not evaluated.
-Viral load in semen 60 and 120 days after the participation of the study.
-Duration for which the body temperature is 37.5 degrees Celsius or higher after the participation of the study.
-Occurrence of adverse events after the participation of the study.
-General condition (bedridden, briefly bedridden, or completely bedridden) at study entry, 14 days, and 30 days after entry

+81-3-3202-7181

June. 14, 2022

none