Safety and efficacy, Tofacitinib, TrIple therapy, Dermatomyositis STTRIDE Study

JRCT ID: jRCT2031240191

Registered date:27/06/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis
• Date of first enrollment: 26/06/2024
• Target sample size: 15
• Study type: Interventional

Intervention(s)

Investigational drug: Tofacitinib
Tofacitinib 5mg/tablet is administered twice daily, one tablet at a time.
The dose may be increased to two tablets of tofacitinib 5 mg/tablet twice daily at the discretion of the investigator or subinvestigator if the patient meets the dose escalation criteria specified in the study protocol at two consecutive assessments during the study period.

Triple therapy:
Triple therapy is defined as the administration of corticosteroids, tacrolimus, and cyclophosphamide starting on Day 1 (for cyclophosphamide, the first dose is administered between Day 1 and Day 3).

Corticosteroids:
Corticosteroids are initiated by oral administration of 1.0 mg/kg/day of prednisolone equivalent (actual weight at screening), taken after meals in 1-3 divided doses per day. Thereafter, the following dose reduction regimen should be followed in principle, although the investigator or subinvestigator may, at his/her discretion, slow down the dose of corticosteroids in patients who meet the criteria specified in the study protocol at two consecutive assessments during the study period.

Tacrolimus:
One dose of 0.0375 mg/kg should be taken twice daily after meals. Thereafter, the target blood trough concentration should be 5-10 ng/mL, and the dose should be adjusted while monitoring blood trough concentrations.

Cyclophosphamide:
Cyclophosphamide: 750 mg/m2 once daily as an intravenous infusion every 4 weeks (Day 1, 29, 57). If cyclophosphamide is administered prior to obtaining consent for this study, it is acceptable to use the body surface area calculated by the Dubois formula using the height and weight at the time of cyclophosphamide administration.
For the second and third doses, the dose and dosing interval should be adjusted according to the white blood cell count from the blood test taken immediately before administration.

Outcome(s)

Primary Outcome

Safety Endpoints
1.Percentage of cytomegalovirus infection and cytomegalovirus disease
2.Percentage of adverse events
3.Percentage of serious adverse events

Efficacy endpoints
1.The percentage of patients who did not require concomitant restricted medications or restricted therapies during the interval between the initiation of trial drug administration and 12 weeks post-initiation, and who were alive at 12 weeks post-initiation.
2.The percentage of patients who remained progression-free for at least 12 weeks following the administration of the trial drug
3.Transition of HRCT score, %FVC, %DLCO, and P/F ratio
4.Total dose of corticosteroids during the trial period
5.Corticosteroid dosage after 12 weeks

Secondary Outcome

1.Transition of blood test values
2.Tofacitinib drug blood concentration
3.Analysis of the relationship between tofacitinib blood drug concentration and efficacy endpoints
4.Analysis of the relationship between tofacitinib blood drug concentration and safety endpoints
5.Analysis of the relationship between the number and type of poor prognostic factors and efficacy endpoints

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Age 18 and over (regardless of gender)
2.Patients with newly diagnosed dermatomyositis who meet the criteria of Bohan and Peter as probable/definite or clinically amyopathic dermatomyositis who meet Sontheimer's criteria
3.Patients with a positive test for anti-MDA5 antibody within 28 days prior to the start of trial drug administration
4.Patients with interstitial pneumonia on chest X-ray or CT
5.Patients with any one of the following conditions A, B, or C
ARapidly progressive interstitial pneumonia
BOxygen saturation is less than 95%
CSerum ferritin level at screening is 500 ng/mL or higher
6.Patients who have been adequately informed of the trial and who have provided written consent, either of their own volition or through their legal representative, are considered to have given their free and informed consent

Exclude criteria

1.Patients who received corticosteroids within 4 weeks (28 days) prior to the start of the investigational drug
2.Patients who received immunosuppressive drugs other than corticosteroids, TNF inhibitors, IL-6 inhibitors, anti-CD20 monoclonal antibodies, JAK inhibitors, intravenous immunoglobulin or plasma exchange therapy within 12 weeks (84 days) prior to the start of the investigational drug
3.Patients with a history of hypersensitivity to the investigational drugs
4.Patients with uncontrolled complications
5.Patients with serious infections
6.Patients with HIV infection, hepatitis B virus, hepatitis C virus infection or a history of such infection
7.Patients with active tuberculosis
8.Patients with AST or ALT greater than 3 times the upper limit of the institutional reference value
9.Patients with a neutrophil count less than 500/mm2
10.Patients with a lymphocyte count less than 500/mm2
11.Patients with a hemoglobin level less than 8 g/dL
12.Patients who are pregnant, possibly pregnant, within 28 days postpartum, or lactating
13.Other patients who are judged by the investigator or sub-investigator to be inappropriate for the safe conduct of this clinical trial.

Related Information

• Primary Sponsor: Furuta Shunsuke
• Source(s) of Monetary Support: Chiba University Hospital