E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012941 |
E.1.2 | Term | Diffuse scleroderma |
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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 assess in patients with diffuse scleroderma the effects of the serotonin receptor antagonist Terguride on established biomarkers of the disease. |
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E.2.2 | Secondary objectives of the trial |
1 To assess the safety of Terguride in SSc patients. 2 To assess improvement in skin fibrosis as assessed by the modified Rodnan skin score. 3 To assess improvement on quality of life using the Scleroderma Health Assessment Questionnaire (SHAQ). 4 To assess the improvement in lung functions as measured by CO diffusion capacity (DLCO) and Forced Vital Capacity (FVC).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients of age between > 18 and < 75 years 2. Patients fulfilling the American College of Rheumatology criteria for systemic sclerosis (SSc) 3. Diffuse cutaneous SSc (dcSSc) according to the LeRoy criteria 4. Female patients of child bearing potential must be using a double-barrier local contraception, i.e. intra-uterine device plus spermicidal gel, or spermicidal gel plus condom up to Study Completion visit 5. Male patients must be using a double-barrier local contraception, i.e., spermicidal gel plus condom, for the entire duration of the study, up to Study Completion visit 6. Capability of understanding the nature of the study and giving written informed consent 7. Willingness and ability to comply with the study protocol for the duration of the study
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E.4 | Principal exclusion criteria |
1 Major surgery within two months prior to treatment start 2 Any of the following abnormal baseline hematological values • Hb < 10g/dl • WBC < 3.0 x 10^9/l • Neutrophils < 1.5 x 10^9/l • Platelets < 100 x 10^9/l 3 Any of the following abnormal baseline liver function tests: • Serum bilirubin > 2.0 x upper normal limit • ALAT and/or ASAT > 5.0 x upper normal limit 4 The following abnormal baseline renal function test: • Serum creatinine > 1.5 mg/dl • Creatinine clearance < 50 ml/min according to modified Cockcroft-Gault criteria: [CLcrea = Weight (kg) x (140 – Age)/72 x serum creatinine concentration] For male: x 1, for female: × 0.85 5 Renal crisis (acute onset of renal failure, moderate to marked hypertension, and normal urine sediment with mild proteinuria) in the 2 months prior to treatment 6 All Cardiovascular: clinically relevant abnormalities, i.e. myocardial infarction within the prior six months, cardiac arrhythmia requiring medication, evidence of fibrosis on heart valves, or uncontrolled hypertension 7 Abnormal cardiac function or non compensated active heart disease (* class II of NYHA classification) 8 Lung • FVC < 50% predicted • CO diffusion capacity < 40% predicted 9 Gut • Pseudo obstruction • Malabsorption requiring parenteral nutrition 10 History of psychiatric disabilities, seizures or central nervous system disorders thought to be clinically relevant in the opinion of the Investigator that could interfere with informed consent or adequate follow-up 11 Treatment with other potentially disease modifying agents during the last 3 months, including prednisone or corticosteroid equivalent in doses higher than 15 mg/d. Doses of prednisone lower than 15 mg/d are allowed 12 Serious (grade 3-4) uncontrolled intercurrent infections 13 Evidence or history of drug or alcohol abuse 14 Participation in any investigational drug study within 60 days preceding treatment start or during the study 15 Pregnancy or breast feeding women 16 Any condition which in the judgment of the Investigator would place the subject at undue risk or interfere with the results of the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary activity endpoints are changes of biomarkers from skin biopsies and plasma and serum biomarkers at the EOS-visit compared to baseline (Day 0). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |