Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Diffuse Cutaneous Systemic Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 27 January 2025
• Main ID: NCT04440592
• Date of registration: 17/06/2020
• Prospective Registration: Yes
• Primary sponsor: Mitsubishi Tanabe Pharma America Inc.
• Public title: Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Diffuse Cutaneous Systemic Sclerosis
• Scientific title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Subjects With Diffuse Cutaneous Systemic Sclerosis
• Date of first enrolment: February 5, 2021
• Target sample size: 76
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04440592
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belgium, Canada, Germany, Italy, Poland, Spain, United Kingdom, United States

Contacts

• Name: Head of Medical Science
• Affiliation: Mitsubishi Tanabe Pharma America Inc.

Key inclusion & exclusion criteria

Additional screening criteria check may apply for qualification.

Inclusion Criteria:

- Subjects who meet all the following criteria will be considered eligible to
participate in the study:

1. Must provide signed and dated informed consent form (ICF) to participate in the
study. Subjects must be able to (in the judgment of the Investigator)
understand the nature of the study and all risks involved with participation in
the study. Subjects must be willing to cooperate and comply with all protocol
restrictions and procedures including study visits.

2. Male or female age = 18 years at screening with documented diagnosis of
systemic sclerosis (SSc), as defined using the 2013 ACR/European League Against
Rheumatism (EULAR) criteria.

3. Has diffuse cutaneous form of SSc according to Leroy and Medsger's criteria.

4. Disease duration = 5 years from the first non-Raynaud's phenomenon
manifestation.

5. Has an mRSS of 15 to 45 units at screening and have clinical skin involvement
proximal and distal to the elbows, knees, or both or any truncal involvement,
with or without face involvement.

6. If disease duration is > 24 months defined as time from the first non Raynaud
phenomenon manifestation, subject must fulfill at least 1 of the criteria
listed below that are indicatives of active disease at screening:

1. A documentation of new skin involvement that occurred within the past 9
months, or

2. Increase in mRSS = 3 units within the past 9 months, or

3. Presence of TFRs or,

4. C- reactive protein (CRP) = 6 mg/L, or

5. Erythrocyte sedimentation rate = 28 mm/hr, or

6. Platelet count = 330 x 10^9/L (330,000/microliter).

NOTE: Investigator should exclude all other acute intercurrent illness if
subjects fulfilling laboratory criteria (d, e, f) only.

7. Willing to follow restrictions regarding concomitant medications that are
described.

8. Female subjects who are non-lactating and have a negative urine pregnancy test
at baseline visit prior to receiving the first dose of study drug.

9. Female subjects of childbearing potential and male subjects with partner of
child-bearing potential currently using/willing to use 2 effective methods of
contraception including barrier method as described.

Exclusion Criteria:

- Subjects will be excluded from the study if any of the following criteria apply:

1. Has a history or presence of rheumatic autoimmune diseases other than dcSSc unless
the dominant features of the disease are dcSSc, as determined by the Investigator.

2. Has a pulmonary disease with FVC = 50% of predicted at time of screening.

3. Has a diagnosis of clinically significant resting pulmonary hypertension (if
exceeding estimated right ventricular systolic pressure of > 40 mmHg estimated by
transthoracic echocardiography [unless the right heart catheterization is normal
within the last 6 months] or mean pulmonary artery pressure > 30 mmHg as measured by
right heart catheterization) and requires treatment with more than one oral
medication.

4. Has a cardiac abnormality such as left ventricular failure with ejection fraction <
45%, significant arrhythmia, congestive heart failure (New York Heart Association
Class II-IV), unstable angina, uncontrolled hypertension, or symptomatic pericardial
effusion at screening.

5. Has a history of myocardial infarction in the last 26 weeks prior to screening.

6. Has a history of renal crisis within the past 52 weeks prior to screening.

7. Has a documented history of chronic kidney disease (stage 4-5, an estimated
glomerular filtration rate [eGFR] < 30 mL/min at screening).

8. Presence or history of hepatobiliary disease at screening, determined as clinically
significant by the Investigator after the discussion with the Sponsor Medical
Monitor.

9. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline
phosphatase (ALP) = 2.0 × upper limit of normal (ULN), or total bilirubin > 1.5 ×
ULN at screening.

10. Has a history or presence of clinically significant disease not related to SSc
[neurologic, renal, endocrinal, gastrointestinal cardiovascular, hepatic,
dermatologic, hematological, musculoskeletal, genitourinary, thromboembolic,
advanced arteriosclerosis, hyperthyroidism, moderate to severe hypertension,
immunologic disease, pulmonary (e.g., uncontrolled asthma, emphysema, chronic
obstructive pulmonary disease) or any other disorder] as determined by the
Investigator at screening. Conditions deemed not-clinically significant according to
the Investigator's discretion are acceptable.

11. Has a history or presence of psychiatric disease judged to be clinically significant
by the Investigator and which may interfere with the study evaluation and/or safety
of the subject.

12. Has any clinically significant disease or laboratory abnormality judged to be
clinically significant by the Investigator and which may interfere with the study
evaluation and/or safety of the subject at screening. Laboratory abnormalities
include but not limited to any of the followings: Hemoglobin < 9 g/dL; WBC <
3,000/mm3 (< 3 x 10^9/L); platelets < 100,000/mm3 (<100 x 10^9/L).

13. Has a history of positive hepatitis B surface antigen, hepatitis C antibody, except
for documented cure for the hepatitis B virus (HBV), defined as sustained,
undetectable HBsAg and HBV DNA in serum and adequately treated hepatitis C virus
(HCV) with documentation of sustained virologic response defined as undetectable HCV
RNA at least 12 weeks after the end of treatment.

14. Has a history of positive human immunodeficiency virus (HIV)

15. Has a history of melanoma, familial melanoma (defined as having 2 or more
first-degree relatives, such as parent, sibling, and/or child), or presence of
melanoma and/or lesions suspicious for melanoma at screening.

16. Has a presence of squamous cell carcinoma, basal cell carcinoma, or other malignant
skin lesions. Any suspicious lesions or nevi (Melanocytic Lesions) will be
evaluated. If the suspicious lesion or nevi (Melanocytic Lesions) cannot be resolved
through biopsy or excision, the subject will be excluded from the study.

17. Has history of any other malignancy(ies) in the last 5 years with the exception of
cervical carcinoma in situ.

18. Has a history or planning to receive cell-depleting therapy or bone marrow
transplantation during study treatment period.

19. Has a history of ultraviolet (UV) phototherapy within 6 weeks prior to screening or
planning to receive UV phototherapy during study treatment period.

20. Treatment of SSc disease with

1. Cyclophosphamide, rituximab, or cyclosporine received within 26 weeks prior to
screening.

2. Small molecules such as JAK inhibitors (e.g., tofacitinib) received within 12
weeks prior to screening.

3. Pirfenidone received within 12 weeks prior to screening.

4. Infliximab, cer


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Diffuse Cutaneous Systemic Sclerosis

Intervention(s)

Drug: MT-7117

Drug: Placebo

Primary Outcome(s)

The ACR CRISS composite score (0-1) at Week 52 [Time Frame: Week 52]

Secondary Outcome(s)

Change in Health Assessment Questionnaire Disability Index (HAQ-DI) from baseline up to week 52 [Time Frame: 52 weeks]

Change in Patient Global Assessment from baseline up to week 52 [Time Frame: 52 weeks]

ACR CRISS score responder (CRISS>=0.6) from baseline up to week 52 [Time Frame: 52 weeks]

ACR CRISS Score up to Week 39 [Time Frame: 39 weeks]

Change in Physician Global Assessment from baseline up to week 52 [Time Frame: 52 weeks]

Change in modified Rodnan Skin Score (mRSS) from baseline from baseline up to week 52 [Time Frame: 52 weeks]

Change in percent predicted forced vital capacity (%pFVC) from baseline up to week 52 [Time Frame: 52 weeks]

Secondary ID(s)

MT-7117-G02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors