A trial to compare nintedanib with placebo for patients with scleroderma related lung fibrosis

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2015-000392-28-GB
• Date of registration: 01/09/2015
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim Limited
• Public title: A trial to compare nintedanib with placebo for patients with scleroderma related lung fibrosis
• Scientific title: A double blind, randomised, placebo-controlled trial evaluating efficacy and safety of oral nintedanib treatment for at least 52 weeks in patients with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD) - Nintedanib in SSc-ILD
• Date of first enrolment: 10/11/2015
• Target sample size: 750
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000392-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion criteria

Inclusion criteria:
- Age >= 18 years
- 2013 ACR / EULAR classification criteria for SSc fulfilled
- SSc disease onset (defined by first non-Raynaud symptom) within 7 years
- SSc related Interstitial Lung Disease confirmed by HRCT; Extent of fibrotic disease in the lung >= 10%
- FVC >= 40% of predicted normal
- DLCO 30% to 89% of predicted normal


Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 450
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion criteria:
- AST, ALT >1.5 x ULN
- Bilirubin >1.5 x ULN
- Creatinine clearance <30 mL/min
- Airway obstruction (pre-bronchodilator FEV1/FVC <0.7)
- Other clinically significant pulmonary abnormalities
- Significant pulmonary hypertension
- Cardiovascular diseases
- More than 3 digital fingertip ulcers
- Bleeding risk (such as predisposition to bleeding, fibrinolysis, full-dose anticoagulation, high dose antiplatelet therapy, history of hemorrhagic central nervous system (CNS) event within last year
- international normalised ratio (INR) >2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by >1.5 x ULN)
- History of thrombotic event within last year
- Clinical signs of malabsorption or needing parenteral nutrition
- Previous treatment with nintedanib or pirfenidone
- Treatment with prednisone >10 mg/day, azathioprine, hydroxychloroquine, colchizine, D-penicillamine, sulfasalazine, cyclophosphamide, rituximab, tocilizumab, abatacept, leflunomide, tacrolimus, newer anti-arthritic treatments like tofacitinib and ciclosporine A, potassium para-aminobenzoate
- Unstable background therapy with either mycophenolate mofetil or methotrexate
- Previous or planned hematopoietic stem cell transplantation
- Patients with underlying chronic liver disease (Child Pugh A, B, C hepatic impairment)
- Patients with a history of Scleroderma Renal Crisis


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with Systemic Sclerosis and associated Interstitial Lung Disease
MedDRA version: 20.0 Level: LLT Classification code 10012977 Term: Diffuse systemic sclerosis System Organ Class: 100000004859
MedDRA version: 19.1 Level: LLT Classification code 10036814 Term: Progressive systemic sclerosis System Organ Class: 100000004859
MedDRA version: 20.0 Level: PT Classification code 10042954 Term: Systemic sclerosis pulmonary System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 20.0 Level: LLT Classification code 10025109 Term: Lung involvement in systemic sclerosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 19.1 Level: LLT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Trade Name: Ofev
Product Name: Nintedanib
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Current Sponsor code: BIBF 1120
Other descriptive name: NINTEDANIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Trade Name: Ofev
Product Name: Nintedanib
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Current Sponsor code: BIBF 1120
Other descriptive name: NINTEDANIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To demonstrate efficacy in regard to skin fibrosis at week 52 and to demonstrate an improvement of patient's symptoms at week 52

Timepoint(s) of evaluation of this end point: 1: 52 weeks

Primary end point(s): 1: Annual rate of decline in FVC in mL

Main Objective: To demonstrate a reduction in the annual rate of decline in FVC in mL over 52 weeks

Secondary Outcome(s)

Secondary end point(s): 1: Absolute change from baseline in the mRSS
2: Absolute change from baseline in SGRQ total score
3: Annual rate of decline in FVC in percent predicted
4: Absolute change from baseline in FVC in mL
5: Relative change from baseline (%) of mRSS
6: Time to all-cause mortality
7: Absolute change from baseline at week 52 in CRISS index score
8: Absolute change from baseline in DLCO in percent predicted
9: Absolute change from baseline in digital ulcer net burden
10: Absolute change from baseline in HAQ-DI score
11: Absolute change from baseline in FACIT dyspnoea score

Timepoint(s) of evaluation of this end point: 1: 52 weeks
2: 52 weeks
3: 52 weeks
4: 52 weeks
5: 52 weeks
6: 52 weeks
7: 52 weeks
8: 52 weeks
9: 52 weeks
10: 52 weeks
11: 52 weeks

Secondary ID(s)

2015-000392-28-NL

1199.214

Source(s) of Monetary Support

Boehringer Ingelheim

Ethics review

Status: Approved
Approval date:
Contact: