Lung Diseases, Interstitial
Conditions
Brief summary
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).
Interventions
DRUGNintedanib
Administered twice daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who completed the parent trial 1199.214/1199-0340 per protocol and did not permanently discontinue study treatment * Signed and dated written informed consent in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial * Women of childbearing potential 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 nintedanib treatment initiation, during the trial and for 3 months after last intake of nintedanib. * Further inclusion criteria apply
Exclusion criteria
* Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) \> 3 x Upper Limit of Normal (ULN) * Bilirubin \> 2 x ULN * Creatinine clearance \<30 mL/min calculated by Cockcroft-Gault formula. * Clinically relevant anaemia at investigators discretion. * Bleeding risk, any of the following * Known genetic predisposition to bleeding according to the judgement of the investigator * Patients who require * Fibrinolysis, full-dose therapeutic anticoagulation * High dose antiplatelet therapy. * Hemorrhagic central nervous system (CNS) event after completion of the parent trial 1199.214/1199-0340 * Any of the following after last treatment of 1199.214/1199-0340: * Haemoptysis or haematuria * Active gastro-intestinal bleeding or Gastrointestinal (GI) - ulcers * Gastric antral vascular ectasia (GAVE) * Major injury or surgery * 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. * New major thrombo-embolic events developed after completion of the parent trial 1199.214/1199-0340: * Stroke; * Deep vein thrombosis; * Pulmonary embolism; * Myocardial infarction. * Major surgery performed within the next 3 months * Time period \> 12 weeks between last drug intake in 1199.214 or \> 1 week between last nintedanib intake in trial 1199-0340 and Visit 2 of this trial * Usage of any investigational drug after completion of 1199.214/1199-0340 or planned usage of an investigational drug during the course of this trial. * A disease or condition which 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 * 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 * Known hypersensitivity to the trial medication or its components (i.e. soya lecithin). * Women who are pregnant, nursing, or who plan to become pregnant while in the trial * Previous enrolment in this trial * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Any Adverse Event (AE) Over the Course of the Trial | First trial medication intake up to last trial drug intake, plus 7 days residual effect period, up to approximate 60 months. | Number of patients with any adverse event (AE) over the course of the trial. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czechia, Denmark, Finland, France, Germany, Greece, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States
Participant flow
Recruitment details
This was a prospective, open-label extension trial to assess long-term safety and tolerability of nintedanib in patients with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD) who had completed treatment (including the follow-up visit or end of treatment/study visit, respectively) of the randomised, double-blind, placebo-controlled parent trial 1199.214 or trial 1199-0340.
Pre-assignment details
Only patients with SSc-ILD who completed one of the parent trials on treatment (i.e., did not discontinue treatment early) were eligible and were included in this trial if they fulfilled all the inclusion criteria and did not present any of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Nintedanib Patients with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD) who took part in the parent trials 1199.214 (Nintedanib or Placebo) or 1199-0340 (Nintedanib). Patients continued in this trial and received Nintedanib 150 mg (milligram) twice daily (bid) unless they had reduced their dose to 100 mg bid trial medication (Nintedanib or Placebo) in the parent trial.
Patients receiving 100 mg bid trial medication at the end of the parent trial could receive either Nintedanib 100 mg bid or 150 mg bid at the discretion of the investigator. | 444 |
| Total | 444 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 120 |
| Overall Study | Covid-19 related | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other than listed above | 15 |
| Overall Study | Withdrawal by Subject | 39 |
Baseline characteristics
| Characteristic | Nintedanib |
|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 406 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants |
| Race (NIH/OMB) Asian | 110 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 308 Participants |
| Sex: Female, Male Female | 335 Participants |
| Sex: Female, Male Male | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 444 |
| other Total, other adverse events | 425 / 444 |
| serious Total, serious adverse events | 198 / 444 |
Outcome results
Primary
Number of Patients With Any Adverse Event (AE) Over the Course of the Trial
Number of patients with any adverse event (AE) over the course of the trial.
Time frame: First trial medication intake up to last trial drug intake, plus 7 days residual effect period, up to approximate 60 months.
Population: Treated Set (TS): all patients who signed informed consent and received at least 1 dose of trial medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nintedanib | Number of Patients With Any Adverse Event (AE) Over the Course of the Trial | 441 Participants |