E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diffuse Cutaneous Systemic Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse Cutaneous Systemic Sclerosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012977 |
E.1.2 | Term | Diffuse systemic sclerosis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
•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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (Appendix 1). 3.Has diffuse cutaneous form of SSc according to Leroy and Medsger's criteria (Appendix 1). 4.Disease duration ≤ 5 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 > 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: 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 tendon friction rubs (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. |
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E.4 | Principal exclusion criteria |
1.Has a history or presence of rheumatic autoimmune diseases other than dcSSc unless the dominant features of the current disease are from dcSSc, as determined by the Investigator after the discussion with the Medical Monitor 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, endocrine, 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 11. Has a history or presence of serious or clinically significant (as judged by the Investigator) psychiatric disorder including but not limited to, anxiety disorder, depression, and bipolar disorder that may 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 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 10^9g/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 EOT 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.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 and 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 ultraviolet (UV) phototherapy during study treatment period 20.Treatment of SSc disease with medication outlined in the protocol 21.Treatment with afamelanotide or other MC1R agonist within 12 weeks before screening visit 1 22.Treatment with any drugs or supplements which, in the opinion of the Investigator, may interfere with the objectives of the study or safety of the subject 23.Has previously exposed to MT-7117 (this does not include placebo treated subjects)
A full list of the exclusion criteria can be found in section 9.4 of the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The American College of Rheumatology Composite Response Index in Diffuse Systemic Sclerosis (ACR CRISS) composite score (0-1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | 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 Endpoint - At study visits
Pharmacokinetics Endpoint - plasma PK concentrations of MT-7117: at study visits
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Spain |
Germany |
Italy |
Belgium |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |