Diffuse Cutaneous Systemic Sclerosis MedDRA version: 21.0 Level: LLT Classification code 10012977 Term: Diffuse systemic sclerosis System Organ Class: 100000004859
Conditions
Sponsors
Mitsubishi Tanabe Pharma Development America (MTDA), Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 aged 18 to 75 years inclusive 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 = 3 years from the first non-Raynaud's phenomenon manifestation. 5. Has an modified Rodnan Skin Score (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 > 18 months defined as time from the first non-Raynaud phenomenon manifestation, subject must fulfil at least 1 of the criteria listed below that are indicatives of active disease at screening: a. A documentation of new skin involvement that occurred within the past 9 months, or b. Increase in mRSS = 3 units within the past 9 months, or c. Presence of TFRs or, d. C- reactive protein = 6 mg/L, or e. Erythrocyte sedimentation rate = 28 mm/hr, or f. Platelet count = 330 x 10^9/L (330,000/microliter). 7. Willing to follow restrictions regarding concomitant medications that are described in Appendix 2. 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 two effective methods of contraception including barrier method as described in Appendix 3. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 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 or diffusion capacity of the lung for carbon monoxide (DLco) = 45% of predicted (hemoglobin corrected) 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 1.5 × ULN at screening. 9.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. 10.Has a history or presence of serious or clinically significant (as judged by the Investigator) psychiatric disorders including but not limited to, anxiety disorder, depression, and bipolar disorder, that make a subject unlikely or unable to complete the study or comply with study procedures and requirements, impact the subject’s ability to participate in the study and/or interfere with the study evaluation and/or safety of the subject. 11.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). 12.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 EOT. 13.Has a history of positive human immunodeficiency virus (HIV). 14.Has a history of melanoma, familial melanoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of MT-7117 treatment in subjects with diffuse cutaneous systemic sclerosis (dcSSc) using the American College of Rheumatology Composite Response Index in Diffuse Systemic Sclerosis (ACR CRISS) at Week 52.;Secondary Objective: •To evaluate the efficacy of MT-7117 treatment for up to 52 weeks using patient-reported outcomes (PROs) as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and Patient Global Assessment. •To evaluate the efficacy of MT-7117 treatment for up to 52 weeks on pulmonary function as measured by percent predicted forced vital capacity (%pFVC). •To evaluate the efficacy of MT-7117 treatment for up to 52 weeks using the Physician Global Assessment. •To evaluate the efficacy of MT-7117 treatment for up to 52 weeks using the modified Rodnan Skin Score (mRSS). •To evaluate ACR CRISS at Weeks 16, 26, and 39. •To evaluate ACR CRISS Score improvement proportion up to 52 weeks.;Primary end point(s): The American College of Rheumatology Composite Response Index in Diffuse Systemic Sclerosis (ACR CRISS) composite score (0-1) ;Timepoint(s) of evaluation of this end point: at week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint •Change in HAQ-DI from baseline at Weeks 16, 26, 39, and 52. •Change in Patient Global Assessment from baseline at Weeks 16, 26, 39, and 52. •Change in percent predicted forced vital capacity (%pFVC) from baseline at Weeks 16, 26, 39, and 52. •Change in Physician Global Assessment from baseline at Weeks 16, 26, 39, and 52. •Change in mRSS from baseline at Weeks 16, 26, 39, and 52. •ACR CRISS Score at Weeks 16, 26, and 39. •ACR CRISS Score improvement at Weeks 16, 26, 39 and 52: Proportion of subjects with 25% improvement in mRSS, HAQ-DI, Patient Global Assessment, Physician Global Assessment, or = 5% improvement in FVC for at least 3 of the 5 ACR CRISS measures. •ACR CRISS score responder (CRISS = 0.6) at Weeks 16, 26, 39, and 52. Safety Endpoint(s) •Treatment-emergent adverse events ([TEAEs] including serious adverse events [SAEs], adverse events leading to withdrawal, and adverse events of special interest [AESIs]). •Physical examination. •Vital signs (blood pressure, pulse rate, respiratory rate, and body temperature). •Clinical laboratory examinations (hematology, coagulation, biochemistry, and urinalysis), including liver function markers (ALT, AST, gamma glutamyl transpeptidase [GGT], ALP, direct and total bilirubin). •12-lead electrocardiogram (ECG). •Nevi (Melanocytic Lesions) appearance (assessed by a dermatologist or other qualified site staff). Any nevi (Melanocytic Lesions) undergoing change of clinical concern during active treatment will be biopsied for follow-up and evaluated by a central pathology laboratory. Pharmacokinetics Endpoint •Assessment of plasma PK concentrations of MT-7117 measured at scheduled visits;Timepoint(s) of evaluation of this end point: Secondary Endpoint: •Change in HAQ-DI, Patient Global Assessment, %pFVC, mRSS : From baseline at weeks 16, 26, 39 and 52 • ACR CRISS score: at weeks 16, 26 and 39 • CRISS Score improvement : at weeks 16, 26, 39 and 52 Safety E | — |
Countries
Belgium, Canada, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactSonia J. Oosman
Mitsubishi Tanabe Pharma Development America (MTDA), Inc.
Outcome results
None listed