E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Sclerosis |
Sclerosi sistemica |
|
E.1.1.1 | Medical condition in easily understood language |
Systemic Sclerosis |
sclerosi sistemica |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate safety and tolerability of 8-week oral administration of SAR100842 in patients with diffuse, cutaneous systemic sclerosis. |
valutare la sicurezza e la tollerabilità di SAR100842 somministrato per via orale per 8 settimane in pazienti con sclerosi sistemica cutanea diffusa |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacodynamic effect of SAR100842 in patients with systemic sclerosis as measured by disease related biomarkers and Lysophoshatidic acid (LPA) receptor signaling markers in blood and skin To explore the effect of SAR100842 on skin thickness in patients with systemic sclerosis as measured by the Modified Rodnan Skin score (mRSS) To explore the effect of SAR100842 on quality of life as measured by the Scleroderma Modified Health Assessment Questionnaire (SHAQ) |
• determinare l’effetto farmacodinamico (PD) di SAR100842 in pazienti con sclerosi sistemica cutanea diffusa, misurato da biomarkers correlati alla malattia e dai markers che esprimono il recettore dell’acido lipofosfatidico (LPA) nel sangue e nella cute; • analizzare l’ effetto di SAR100842 sull’ispessimento cutaneo nei pazienti con sclerosi sistemica cutanea diffusa, misurato attraverso il “Modified Rodnan Skin score” (mRSS); • analizzare l’ effetto di SAR100842 sulla qualità di vita misurata tramite lo “Scleroderma Modified Health Assessment Questionnaire” (SHAQ). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients who meet the American College of Rheumatology (ACR) criteria for systemic sclerosis with diffuse cutaneous involvement and <36 months since the onset of the first systemic sclerosis manifestation other than Raynaud's phenomenon and have a Modified Rodnan Skin Score (mRSS) ≥ 15 and an area of definite involvement of the dorsal forearm that is considered amenable to repeated 4mm skin biopsies.</ |
pazienti che rispondono ai criteri dell’”American College of Rheumatology” (ACR) per la sclerosi sistemica, con coinvolgimento cutaneo diffuso ed esordio della prima manifestazione di Sclerosi Sistemica SSc < a 36 mesi, con esclusione del fenomeno di Raynaud, e con un punteggio di ispessimento cutaneo ≥ a 15 e un’area di coinvolgimento della parte dorsale dell’avambraccio ben determinata, che possa essere sottoposta a ripetute biopsie cutanee di 4 mm. |
|
E.4 | Principal exclusion criteria |
1. Patients with high dose or unstable low dose immunosuppressive drugs, cytotoxic, anti-fibrotic or glucocorticoids drugs at least 4 weeks prior to screening 2.Serum creatinine > 2.0 mg/dL 3. Gastrointestinal involvement preventing oral administration of study drug 4. Severe cardiac and/or pulmonary disease |
1.pazienti trattati con alte dosi o con dose bassa ma instabile di farmaci immunosoppressori, citotossici, anti-fibrotici o glucocorticoidi, nelle 4 settimane precedenti lo screening; 2.valori di creatinina sierica >2.0 mg/dL; 3.condizione gastrointestinale che possa impedire la somministrazione orale del farmaco di studio; 4. patologia cardiaca e/o polmonare di grado severo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability during the 8 week treatment period (Number of patients reporting adverse events)</ |
Sicurezza e tollerabilità durante le 8 settimane di trattamento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 8 weeks |
Fino a 8 settimane |
|
E.5.2 | Secondary end point(s) |
Pharmacodynamic changes from baseline to End of Treatment Visit in biomarkers obtained from blood and skin Change from baseline to End of Treatment Visit in skin severity score (mRSS) and in Scleroderma health assessment questionnaire (SHAQ)</ |
-Variazioni farmacodinamiche dalla visita basale alla visita di fine trattamento dei biomarkers cutanei ed ematologici •variazioni nello Skin Severity score (mRSS) e nello Scleroderma health assessment questionnaire (SHAQ) dalla visita basale alla visita di fine trattamento. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Day 1 and 8 weeks |
al giorno 1 e alla ottava settimana |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Switzerland |
United States |
|
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
|
|
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 | 12 |
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 | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |