An open-label extension trial to assess the long term safety of nintedanib in patients with *Systemic Sclerosis associated Interstitial Lung Disease* (SSc-ILD)

Systemic Sclerosis (SSc) is an orphan, devastating disease of unknown etiology.
Patients suffer from multiple organ fibrosis, leading to abnormalities of the
skin, lungs, vascular abnormalities, kidney disease, oesophageal and
gastrointestinal involvement (hypomotility), cardiac disorders and muscle
disease.

No approved SSc treatment is available, and no treatment is considered to be
the gold standard for chronic treatment of SSc-ILD.

The rationale for development of nintedanib in SSc-ILD is based on the
pre-clinical evidence of potential effects in SSc and clinical evidence of
antifibrotic activity of nintedanib in Idiopathic Pulmonary Fibrosis (IPF)
along with an acceptable safety profile.

This clinical trial is planned as an open label extension trial following the
parent trial SENSCISTM (1199.214) and 1199-0340, the latter investigating the
safety and efficacy of nintedanib in Systemic Sclerosis interstitial lung
disease.

This clinical trial is an open-label extension trial of the main study
SENSCISTM (1199.214) and 1199-0340 to further evaluate the safety of long term
treatment with nintedanib in patients with scleroderma related lung fibrosis.
Also, in this trial, patients who experienced benefits on using nintedanib in
the SENSCISTM (1199.214) or 1199-0340 study, get the oppertunity to keep using
nintedanib until it becomes availble in a different way for this group of
patients.

This is a multi-centre, multi-national, prospective, open label extension
clinical trial. It is anticipated that approximately 400 patients with SSc-ILD
will complete the parent trial SENSCISTM or 1199-0340 as planned. These
patients will be eligible for enrolment in this extension trial.

After signing Informed Consent and if all eligibility criteria are met,
patients will initiate treatment with nintedanib (Visit 2).

The trial is estimated to last a total of approximately 3 years. The trial will
end either when nintedanib is available on the market or will be made otherwise
available to the patient, it is not expected that this will be a lot sooner
than 3 years after the start of this study. If after 3 years, nintedanib is
still not available on the market, this trial will continue or nintedanib will
be made otherwise available for the patient so that it certain that the
patients can be treated with nintedanib anyhow.

During this trial, treatment will be stopped if a reason for withdrawal is met.

See protocol section 3.1.

All patients will be treated with nintedanib in this trial; there is no active
comparator or placebo.

See also protocol section 4.1.1 - 4.1.3.

Duration: this trial ends when the medication becomes available (on the
marktet) for these patients, it is expected that this study will last three
years. Six to seven visits will take place within the first year. In the next
two years, there will be full visits every 16 weeks and visits for only blood
drawing every 16 weeks. That means that a patient needs to visit the hospital
every 8 weeks. In total (expecting that this study will last for three years)
26 visits will take place.

Burden: During the 'a' vists, only bloodsamples will be taken: 5x during the
first year, then once after 8 weeks and then every 16 weeks.
Completing questionnaires: 3x during the first year, then every 16 weeks and
during the end of treatment visit.
Physical examination and vital signs (blood pressure and pulse): every visit
except for the 'a' visits.
Digital Ulcers assesment: 6x during the first year and then every 16 weeks.
Pregnancy testing (if applicable): every 4-6 weeks.
Blood- and urine tests: 12x during the first year and then every 8 weeks (every
visit)
Lungfunction testing (FVC): 7x during the first year and then every 16 weeks
ECG: 3x during the entire study.

Risks: Known dide effects of the use of nintedanib are mostly gastrointestinal
relates (diarrhea, nausea, abdominal pain, vomiting) and liverfunction
disorders. Liverfunction will be check every visit. Side effects can be treated
symptomatic in most cases. Blood drawing can be painful and can cause
bruisings. Lungfunction tests are standard for this disease but can be
exhausting. The stickers used for making the ECG's can cause minor skin
irritations.