E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Sclerosis associated Interstitial Lung Disease |
Patients atteints de sclérodermie systémique avec atteinte interstitielle
pulmonaire |
|
E.1.1.1 | Medical condition in easily understood language |
scleroderma related lung fibrosis |
sclérodermie systémique avec atteinte pulmonaire |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036814 |
E.1.2 | Term | Progressive systemic sclerosis |
E.1.2 | System Organ Class | 100000004859 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042954 |
E.1.2 | Term | Systemic sclerosis pulmonary |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025109 |
E.1.2 | Term | Lung involvement in systemic sclerosis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
E.1.2 | System Organ Class | 100000004859 |
|
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 |
The main objective is to assess long term safety of treatment with oral nintedanib in patients
with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD). |
L’objectif principal de cette étude est d’évaluer la sécurité à long terme du nintedanib chez des patients atteints de SSc-ILD |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
Non applicable |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who completed the SENSCISTM trial per protocol and did not permanently discontinue blinded treatment
2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial
3. Women of childbearing potential1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly as well as one barrier method for 28 days prior to and 3 months after nintedanib administration. A list of contraception methods meeting these criteria is provided in the patient information. |
1.Patient ayant complété l’étude SENSCIS™ selon le protocole et n’ayant pas interrompu de façon permanente le traitement en aveugle.
2.Signature d’un formulaire de consentement éclairé conformément aux Bonnes Pratiques Cliniques (BPC) et à la législation locale avant toute procédure de l’étude.
3.Patiente en âge de procréer devant être prête et capable d’utiliser des méthodes de contraception hautement efficace (selon la définition de l’ICH M3(R2)) ayant un taux d’échec <1% par an dans le cadre d’une utilisation correcte et permanente ainsi qu’une méthode de type barrière depuis au moins 28 jours précédant l’introduction du nintedanib, pendant l’étude ainsi que 3 mois après la dernière prise de nintedanib.
|
|
E.4 | Principal exclusion criteria |
1. AST, ALT > 3 x ULN
2. Bilirubin > 2 x ULN
3. Creatinine clearance <30 mL/min
4. Clinically relevant anaemia at investigators discretion.
5. Bleeding risk, any of the following
a. Known genetic predisposition to bleeding according to the judgement of the investigator
b. Patients who require
i. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin)
ii. High dose antiplatelet therapy. [Note: Prophylactic low dose heparin or heparin flush as needed for maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 I.U. s. c. per day), as well as prophylactic use of antiplatelet therapy (e.g.acetyl salicylic acid up to 325 mg/day, or clopidogrel at 75 mg/day, or equivalent doses of other antiplatelet therapy) are not prohibited].
c. Hemorrhagic central nervous system (CNS) event after completion of the parent trial SENSCISTM
d. Any of the following after last treatment of SENSCISTM:
i. Haemoptysis or haematuria
ii. Active gastro-intestinal bleeding or GI – ulcers
iii. Gastric antral vascular ectasia (GAVE)
iv. Major injury or surgery (investigators judgement).
e. Coagulation parameters: International normalised ratio (INR) >2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by >1.5 x ULN at Visit 1.
6. New major thrombo-embolic events developed after completion of the parent trial
SENSCISTM :
a. Stroke;
b. Deep vein thrombosis;
c. Pulmonary embolism;
d. Myocardial infarction.
7. Major surgery (major according to the investigator’s assessment) performed within the next 3 months
8. Time period > 12 weeks between last drug intake in SENSCISTM and Visit 2 of this trial.
9. Usage of any investigational drug after completion of the parent trial SENSCISTM or planned usage of an investigational drug during the course of this trial.
10. A disease or condition which in the opinion of investigator may put the patient at risk because of participation in this trial (e.g. clinically relevant intestinal pseudoobstruction) or limit the patient’s ability to participate in this trial
11. Chronic alcohol or drug abuse or any condition that, in the investigator’s opinion, makes them an unreliable trial subject or unlikely to complete the trial
12. Known hypersensitivity to the trial medication or its components (i.e. soya lecithin).
13. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
14. Previous enrolment in this trial |
1.ASAT, ALAT >3 x ULN (Upper Limit of Normal)
2.Bilirubine > 2 × ULN
3.Clairance de la créatinine < 30 ml/min (calculée par la formule de Cockcroft-Gault).
4.Anémie cliniquement significative selon l’investigateur
5.L’un des facteurs de risque hémorragique suivants :
a. Prédisposition génétique connue aux saignements selon l’investigateur.
b. Patient qui nécessite :
i. Fibrinolyse, traitement anticoagulant à pleine dose (par exemple anti-vitamine K, inhibiteur direct de la thrombine, héparine, hirudine)
ii. Traitement antiagrégant plaquettaire à forte dose.
Remarque : L’administration d’héparine à faible dose à titre préventif (par exemple énoxaparine 4 000 UI sc par jour) ou des rinçages héparinés comme nécessaire pour l’entretien d’un dispositif intraveineux à demeure, ainsi que l’administration d’un antiagrégant plaquettaire à titre préventif (par exemple acide acétylsalicylique jusqu’à 325 mg/jour ou clopidogrel à 75 mg/jour ou dose équivalente d’un autre antiagrégant plaquettaire), ne sont pas interdits.
c. Antécédents d’hémorragie du système nerveux central (SNC) depuis la sortie de l’étude SENSCIS™.
d. L’un des événements suivants depuis l’arrêt du traitement de l’étude SENSCIS™:
i. Hémoptysie ou hématurie
ii. Saignement gastro-intestinal ou ulcère gastro-intestinal actif
iii. Ectasie vasculaire de l’antre gastrique
iv. Blessure ou intervention chirurgicale majeure (selon le jugement de l’investigateur).
e. Paramètres de la coagulation : International normalized ratio (INR) >2, temps de prothrombine (TP) et temps de thromboplastine partielle (PTT) > 1,5 x ULN à la visite 1.
6.L’une des évènements thrombo-embolique majeur survenu depuis la sortie de l’étude SENSCIS™ :
a. Accident Vasculaire Cérébral
b. Thrombose veineuse profonde
c. Embolisme pulmonaire
c. Infarctus du myocarde
7.Une intervention chirurgicale majeure (majeure selon le jugement de l’investigateur) programmée dans les 3 mois suivant l’inclusion.
8.Une durée de plus de 12 semaines entre l’arrêt du traitement de l’étude SENSCIS™ et la Visite 2 de cette étude.
9.Prise d’un médicament expérimental depuis la sortie de l’étude SENSCIS™ ou prévu en cours d’étude.
10.Autre maladie ou situation, selon le jugement de l’investigateur, pouvant exposer le patient à un risque lors de sa participation à celle-ci (exemple : pseudo obstruction intestinale cliniquement significative) ou limitant la capacité du patient à participer à l’étude.
11.Alcoolisme, toxicomanie, ou toute autre condition qui selon le jugement de l’investigateur, interfère sur les résultats de l’étude ou empêche la participation complète du patient.
12.Hypersensibilité connue au médicament à l’étude ou à l’un de ses excipients (par exemple lécithine de soja).
13.Femme enceinte, qui allaite ou qui projette de débuter une grossesse au cours de l’étude.
14.Inclusion antérieure dans cette étude |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) The primary endpoint is the incidence of overall adverse events over the course of this extension trial. |
Incidence de tous les évènements indésirables survenant au cours de l'étude d'extension |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) up to 34 months |
1) Jusqu'à 34 mois |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 85 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Chile |
China |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
India |
Ireland |
Israel |
Italy |
Japan |
Malaysia |
Mexico |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Sweden |
Switzerland |
Thailand |
United Kingdom |
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
|
LVLS |
Dernière visite du dernier patient de l'étude |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
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 | 10 |