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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02597933




Registration number
NCT02597933
Ethics application status
Date submitted
8/10/2015
Date registered
5/11/2015
Date last updated
13/12/2019

Titles & IDs
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)
Secondary ID [1] 0 0
2015-000392-28
Secondary ID [2] 0 0
1199.214
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Scleroderma, Systemic 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nintedanib
Treatment: Drugs - Placebo

Experimental: Nintedanib - patient receives capsules containing nintedanib twice a day

Placebo Comparator: Placebo - patient receives capsules identical to those containing active drug


Treatment: Drugs: Nintedanib


Treatment: Drugs: Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annual Rate of Decline in Forced Vital Capacity (FVC) Over 52 Weeks
Timepoint [1] 0 0
up to week (wk) 52 after the start of administration
Secondary outcome [1] 0 0
Absolute Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52
Timepoint [1] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [2] 0 0
Absolute Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 52.
Timepoint [2] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [3] 0 0
Annual Rate of Decline in FVC in Percentage (%) Predicted Over 52 Weeks
Timepoint [3] 0 0
up to 52 weeks after the start of administration
Secondary outcome [4] 0 0
Absolute Change From Baseline in FVC in mL at Week 52
Timepoint [4] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [5] 0 0
Relative Change From Baseline [%] of mRSS at Week 52
Timepoint [5] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [6] 0 0
Time to Death
Timepoint [6] 0 0
From date of first trial drug intake up to date of death or last contact date (ie., up to 100 weeks)
Secondary outcome [7] 0 0
The Percentage (%) of Responder Based on Combined Response Index in Systemic Sclerosis (CRISS) at Week 52
Timepoint [7] 0 0
Week 52
Secondary outcome [8] 0 0
Absolute Change From Baseline in Carbon Monoxide Diffusion Capacity (DLco) in % Predicted at Week 52
Timepoint [8] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [9] 0 0
Absolute Change From Baseline in Digital Ulcer Net Burden at Week 52
Timepoint [9] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [10] 0 0
Absolute Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52
Timepoint [10] 0 0
Baseline and up to 52 weeks after the start of administration
Secondary outcome [11] 0 0
Absolute Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnoea Score at Week 52
Timepoint [11] 0 0
Baseline and up to 52 weeks after the start of administration

Eligibility
Key inclusion criteria
Inclusion criteria:

- Age >= 18 years

- 2013 American College of Rheumatology (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 High Resolution Computer Tomography
(HRCT); Extent of fibrotic disease in the lung >= 10%

- FVC >= 40% of predicted normal

- Carbon Monoxide Diffusion Capacity (DLCO) 30% to 89% of predicted normal
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) >1.5 x ULN

- Bilirubin >1.5 x ULN

- Creatinine clearance <30 mL/min

- Airway obstruction (pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/FVC
<0.7)

- Other clinically significant pulmonary abnormalities

- Significant Pulmonary Hypertension (PH)

- Cardiovascular diseases

- More than 3 digital fingertip ulcers or a history of severe digital necrosis requiring
hospitalization or severe other 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, colchicine,
D-penicillamine, sulfasalazine, cyclophosphamide, rituximab, tocilizumab, abatacept,
leflunomide, tacrolimus, newer anti-arthritic treatments like tofacitinib and
cyclosporine 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/11/2018
Sample size
Target
Accrual to date
Final
580
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
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Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Liverpool Hospital - Sydney
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Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
St Vincent's Hospital Melbourne - Fitzroy
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Sydney
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Systemic Sclerosis (SSc) is a devastating disease of unknown etiology. Patients suffer from
multiple organ fibrosis whereas lung fibrosis (interstitial lung disease, ILD) is one of the
main driver for mortality. There is preclinical evidence for efficacy of nintedanib in SSc
and associated ILD (SSc-ILD) and the anti-fibrotic efficacy of nintedanib was proven in
idiopathic pulmonary fibrosis patients, who are presenting a similar pattern regarding lung
fibrosis. Hence it is the purpose of the trial to confirm the efficacy and safety of
nintedanib 150 mg bid in treating patients with SSc-ILD, compared with placebo. The trial
will be conducted as a double blind, randomised, placebo-controlled trial with primary
efficacy evaluation at week 52 and placebo-controlled treatment until last patient out (up to
a maximum of 100 weeks). Respiratory function is globally accepted for assessment of
treatment effects in patients with lung fibrosis. The chosen endpoint (Forced Vital Capacity
(FVC) decline) is easy to obtain and is part of the usual examinations done in patients with
SSc-ILD.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02597933
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries