E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic sclerosis |
Sclerosi sistemica |
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E.1.1.1 | Medical condition in easily understood language |
Systemic sclerosis |
Sclerosi sistemica |
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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 | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 100000004859 |
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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, in comparison with placebo, the efficacy of SAR156597 administered subcutaneously on skin fibrosis in patients with dcSSc. |
Valutare, rispetto a placebo, l¿efficacia di SAR156597,somministrato per via sottocutanea sulla fibrosi cutanea di pazienti affetti da sclerosi sistemica cutanea diffusa (dcSSc).
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E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of SAR156597 compared to placebo on physical/functional disability in patients with dcSSc. -To evaluate the efficacy of SAR156597 compared to placebo on respiratory function in patients with dcSSc. -To evaluate the safety profile of SAR156597 compared to placebo in patients with dcSSc. -To evaluate the potential for immunogenicity (anti-drug antibodies [ADA] response) of SAR156597 in patients with dcSSc. -To evaluate the pharmacokinetics (PK) (trough plasma concentrations) of SAR156597 administered subcutaneously. |
- Valutare l¿efficacia di SAR156597 rispetto a placebo sulla disabilit¿ fisica/funzionale in pazienti affetti da dcSSc. - Valutare l¿efficacia di SAR156597 rispetto a placebo sulla funzionalit¿ respiratoria in pazienti affetti da dcSSc. - Valutare il profilo di sicurezza di SAR156597 rispetto a placebo in pazienti affetti da dcSSc. - Valutare il potenziale di SAR156597 per lo sviluppo di una risposta immunogenica mediata da anticorpi anti-farmaco (ADA) in pazienti affetti da dcSSc. - Valutare la farmacocinetica (PK) attraverso le concentrazioni plasmatiche di SAR156597 somministrato per via sottocutanea. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Systemic Sclerosis according to the American College of Rheumatology/The European League against Rheumatism (ACR/EULAR) 2013 criteria. -Diffuse cutaneous form of SSc according to Leroy's criteria. -Able and willing to sign the written informed consent form with comprehension of its contents and comply with the requirements of the study protocol. |
Sclerosi sistemica secondo i criteri 2013 dell’American College of Rheumatology/European League against Rheumatism (ACR/EULAR) [Collegio americano di reumatologia/Lega Europea contro le malattie reumatiche]; - Forma cutanea diffusa di SSc in base ai criteri di Leroy. - Soggetto in grado e disposto a firmare il Modulo di consenso informato scritto, previa comprensione dei suoi contenuti, e a rispettare i requisiti del protocollo dello studio. |
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E.4 | Principal exclusion criteria |
Age<18yrs Disease duration>36mths from time of 1nonRaynaud's phenomenon manifestation mRSS<10 or>35 at screen and baseline visits History of vasculitis,active or in remission Diag connective tissue diseases(other than SSc)or PM/Scl Pos HIV serology/known history of HIV active or in remission Abnormal hepB and/or hepC tests indicative active/chronic infection:Abnormal HepB tests:Pos HBsAg OR pos total HBcAb with neg hepB surface Ab(HBsAb)/pos total hepB core antibody with pos HBsAb and presence of hepB DNA(HBV DNA) Abnormal HepC tests:Pos antiHCV Ab and pos HCV RNA Pos or 2confirmed indeterminate QTF tests at screen(regardless of prior treatment status) Serious infection(eg pneumonia, pyelonephritis)within 4wk of screen,infection requiring hospitaliz/IV antibiotics within 4wk of screen or chronic bacterial infection(eg osteomyelitis) History of anaphylaxis to any biologic therapy Evidence of any clinically significant,severe/unstable,acute/chronically progressive,uncontrolled infection or medical condition(eg, cerebral,cardiac,pulmonary,renal,hepatic,gastrointestinal or neurologic other than SSc or SScILD)or previous,active/pending surgical disorder,or any condition that may affect pt safety in the judgment of the PI At screen, the% predicted FVC <=75% AND%predicted DLCO after Hgb correction is<=40% History of HF, LVEF <=45%, coronary artery disease,angina,myocardial infarction,ischemic/HCM Any prior history of malignancy or active malignancy including lymphoproliferative diseases(except successfullytreated carcinoma insitu of the cervix,nonmetastatic squamous cell/basal cell carcinoma of the skin)within 5yrs prior to baseline Ischemic ECG changes and/or other clinical significant ECG findings at screen High dose steroids(>10mg/day prednisolone equiv)or change in steroid dose within 4wk prior to screen or during the screen period or expected changes during the study course Previous treat with rituximab within 12mths prior to screen Previous treat with bone marrow transplantation,tot lymphoid irradiation/ablative ultrahigh dose cyclophosphamide Treat with high dose immunosuppressive drug(eg cyclophosphamide>1mg/kg oral/day or>750mg IV/mth;azathioprine>100mg/day;methotrexate>15mg/week;mycophenolate mofetil>2g/day)within 3mths of screen or change in dose within 4wk prior to baseline Treat with etanercept,cyclosporine A,IVIG,rapamycin,Dpenicillamine,tyrosine K inhibitors within 4wk of screen or antithymocyte globulin within 6mths of screen Treat with infliximab,certolizumab,golimumab,abatacept,or adalimumab,tocilizumab within 8wk of screen or anakinra within 1wk of screen Treat with any IMP within 1mth of screen,or 5halflives,if known Abnormal lab tests at screen: ALT or AST>2 times upper limit of ULN Hgb<11 g/100mL(male) &<10 g/100mL(female) Neutrophils<1500/mm^3(except<1000/mm3 for those of African descent) PLT<100 000/mm^3 Creatinine=>150µmol/L Lab parameters may be repeated once during the screen period if felt to be spurious or due to technical error in order to det eligibility Current history of substance and/or alcohol abuse Sanofi current employee/has an immediate family member(eg spouse,parents,child,sibling)Sanofi current employee Currently incarcerated or anticipated/scheduled to be incarcerated during the course of the study Any condition or circumstance that will preclude the pt from following and completing protocol requirements in the opinion of the PI Pregnant or breastfeeding woman Women who are of childbearing potential not protected by highlyeffective contraceptive method(s) of birth control as(defined in the ICF form and/or Appendix G for UK)and/or who are unwilling or unable to be tested for pregnancy Women of childbearing potential must have a confirmed neg pregtest at screen and randomiz visits.They must use effective contraceptive method throughout the entire duration of the study treatment,and for at least 12wk after the last admin of IMP Postmenopausal women must be amenorrheic for at least 12mth |
Per una migliore comprensione, fare riferimento alla sinossi ITA Età<18aa Durata malat>36 mesi dalla 1°manifestaz del fen di nonRaynaud mRSS<10 o>35 allo screen e vis basali Anamnesi di vasculite, att o in remis Diagn malat del tess connett (diversa da SSc) o di PM/Scl PosHIV o nota anamnesi di inf HIV, att o in remiss Test anorm per Epa B e/o epa C indicativi di un'inf att o cronica Test anorm per Epa B: HBsAG pos all'epa B o Ab core tot pos all'epa B (HBcAb) con Ab di superf neg all'epa B o Ab core tot pos con Ag di superf pos e presenza DNA epa B Test anorm epa C Ab pos antiHCV e RNA pos HCV Test QTF pos o 2 conf allo screen (indip prec stato di tratt) Inf grave (es polmonite, pielonefrite) entro 4 sett dallo screen, inf con ospedaliz o somm antibiotici x via EV entro 4 sett dallo screen o infez batt cronica (es osteomielite) Anamnesi anafilassi a qualsiasi terapia biol Prova di qualunque inf o condiz medica CS, grave o instabile, acuta o cronic progr, non controll (es cerebrale, cardiaca, polmonare, renale, epatica, gastrointest o neurol, diversa da SSc o SScILD) o malat chirurg prec att o in atto o qualunque condiz che possa impattare la sicur del pz a giudiz del PI Allo screen FVC predetta <=75% e capacità diffusione polmonare di CO predetta corretta in base valore di Hb <=40%. Storia di insuff cardiaca EF del ventricolo sx <=45%, coronaropatia angina infarto miocardio e cardiomiopatia ischemica/ipertrofica. Ogni precedente anamnesi neoplasia o K maligno att,incluse le malat linfoproliferative nei 5aa precedenti il basale (a eccez del K della cervice in situ trattato con successo, del K della pelle a cell squamose non metastatizzato o a cell basali) modifiche ischem all’ECG e/o altre modifiche CS all’ECG allo screen Alta dose steroidi (>10 mg/die prednisolone equiv); o variaz dose steroidi entro 4 sett prec lo screen o durante il periodo di screen o cambiamenti attesi durante il corso dello studio Precedente tratt con rituximab nei 12 mesi precedenti la visita di screen Precedente tratt con trapianto di midollo osseo, irradiaz tot linfoide o ablaz ad alte dosi di ciclofosfamide Tratt con alta dose di farmaci immunosoppressivi (es. ciclofosfamide>1 mg/kg orale/die o>750 mg IV/mese; azatioprina>100mg/die; metrotrexato>15mg/sett; micofenolato mofetil>2g/die) nei 3 mesi prec lo screen o variaz dose nelle 4 sett precedenti al basale Tratt con etanercept, ciclosporina A, IVIG, rapamicina, Penicillamina D, inibitori della TK entro 4 sett dallo screen o ATG entro 6 mesi dallo screen Tratt con infliximab, certolizumab, golimumab, abatacept o adalimumab, tocilizumab entro 8 sett dallo screen o anakinra nella sett precedente lo screen Tratt con qualunque IMP nel mese precedente lo screen, o nelle 5 emivite, se noto (quello fra i 2che risulta + lungo) Test di lab anormali allo screen ALT o AST>2 volte ULN Hb<11g/100 ml per i maschi e <10 mg/100 ml per le donne NE <1500mm^3 (ad eccez <1000/mm3 per pop Africane) PLT <100000 mm^3 Creatinina = 150 µmol/L nota: i valori di lab possono essere ripetuti 1volta durante il periodo di screen se ritenuti non attendibili o in caso di err tecnico x determ eleggibilità Anamnesi attuale abuso alcol e/o sostanze Attuale impiego c/o Sanofi o parente impiegato Sanofi (coniuge, genitori, figlio, fratello) Attuale condizione/previsione di carcerazione durante il corso dello studio Qualunque condiz o circostanza che può precludere al pz la possibilità di seguire e completare il protocollo a giudizio del PI Donne in gravid o in allat Donne in età fertile che non fanno uso di contrac ad elevata efficacia (vedi modulo di CI) e/o che non vogliono o non sono in grado di eseguire un test di gravidanza. Le donne in età fertile devono avere un test di grav neg allo screen e alle visite di randomiz. Devono utilizzare un metodo contracc efficace durante l'intera durata dello studio e x almeno 12 sett dopo l'ultima somm dell’IMP Donne in menop devono essere in amenorrea da almeno 12 mesi |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in mRSS |
Variazione nel mRSS dal basale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline to Week 24 |
Dal basale alla settimana 24 |
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E.5.2 | Secondary end point(s) |
Change from Baseline in Health Assessment Questionnaire Disability Index (HAD-QI), assessed with SHAQ
Change from baseline in respiratory function as measured by observed Forced Vital Capacity (FVC) Change from baseline in observed Carbon Monoxide Diffusing Lung Capacity (DLco 8corrected for hemoglobin))
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Variazione dal basale nell¿Indice di disabilit¿ del Questionario per la valutazione della salute (HAQ-DI), valutato mediante questionario per la valutazione della salute nella sclerodermia (SHAQ) Variazione dal basale nella funzione respiratoria, misurata in base ai valori osservati di capacit¿ vitale forzata (CVF)
Variazione dal basale della capacit¿ polmonare di diffusione del monossido di carbonio (DLco[corretta per l¿emoglobina])
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
From Baseline to Week 24 |
Dal basale alla settimana 24 |
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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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Argentina |
Austria |
Belgium |
Estonia |
France |
Germany |
Italy |
Mexico |
Poland |
Romania |
Russian Federation |
Ukraine |
United Kingdom |
United States |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |