Study of Pulmonary Rehabilitation in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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The main objectives of this study are: Determine the difference in change from baseline in Six Minute Walk Distance (6MWD) when pulmonary rehabilitation (PR) is added to stable underlying nintedanib therapy in patients with idiopathic pulmonary fibrosis (IPF) Determine the difference in change in Quality of Life (QoL) when pulmonary rehabilitation (PR) is added to stable underlying nintedanib therapy in patients with idiopathic pulmonary fibrosis (IPF) Determine if there is an enduring effect in 6MWD, QoL and lung function from pulmonary rehabilitation (PR) when pulmonary rehabilitation (PR) is added to stable underlying nintedanib therapy in patients with idiopathic pulmonary fibrosis (IPF)

Official Title
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Study of Pulmonary Rehabilitation In Nintedanib Treated Patients With IPF: Improvements in Activity, Exercise Endurance Time, and QoL

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Nintedanib
* Other: Pulmonary rehabilitation program


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients being treated with a stable dose of nintedanib 150 mg BID for up to 30 months. Patients who have recently started nintedanib 150 mg BID and have started by the day of randomization must be on nintedanib 150 mg BID a minimum of 10 days by the first day of pulmonary rehabilitation. Age ≥ 40 years at screening Women of childbearing potential (WOCBP) 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. A list of contraception methods meeting these criteria is provided in the patient consent form Signed and dated written informed consent in accordance with ICH-GCP (International Council on Harmonization and Good Clinical Practice) and local legislation prior to admission to the trial Confirmed diagnosis of IPF according to 2011 American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines by lung biopsy or High Resolution Computed Tomography (HRCT)(based upon INPULSIS criteria, (if biopsy only or HRCT done > 24 months prior to screening, a new HRCT to be done after consent and prior to or up to 7 days after Visit 2 for quantitative lung fibrosis score (QLF) for disease characterization) Forced Vital Capacity (FVC) ≥ 45% of predicted by the NHANES equation or equivalent (after discussion with Clinical Monitor), historical within past 30 days can be used. Carbon monoxide Diffusion Capacity (DLCO) (corrected for hemoglobin [Hgb]) 30-79% of predicted FEV1/FVC greater than/equal to .7 Physically capable of performing both a 6 minute walk test and work rate cycle ergometry (sub-study patients), must successfully complete the practice tests for the 6 minute walk test, per the instructions. Potential sub-study patients that require supplemental oxygen or cannot complete the incremental work rate cycle ergometry test will not participate in the sub-study, but will qualify for the main study. Exclusion criteria: Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned within 6 months after screening, e.g. hip replacement which could interfere with the ability to participate in pulmonary rehabilitation. Any documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial Previous enrolment in this trial (except for rescreening) Currently enrolled in another interventional investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s) Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial Women who are pregnant, nursing, or who plan to become pregnant in the trial Previous participation in pulmonary rehabilitation program within 45 days prior to signing consent

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nintedanib treatment alone<br> | Drug: Nintedanib<br>* stable dose<br>|
| Experimental: Nintedanib with a pulmonary rehabilitation program<br> | Drug: Nintedanib<br>* stable dose<br>Other: Pulmonary rehabilitation program<br>* 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the 6 Minute Walk Test (6MWD) at 12 Weeks | Absolute change from baseline in the 6 minute walk distance (6MWD) test at 12 weeks. The last assessment before treatment period start (included) will be used as baseline. If the baseline value is missing and the screening value is available, then the baseline value will be defined as the screening value taken closest to baseline date. | Baseline (day 1) and week 12 (day 85). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the 6 Minute Walk Test (6MWD) at 24 Weeks | Absolute change from baseline in the 6 minute walk distance (6MWD) test at 24 weeks. The last assessment before treatment period start (included) will be used as baseline. If the baseline value is missing and the screening value is available, then the baseline value will be defined as the screening value taken closest to baseline date. | Baseline (day 1) and week 24 (day 169). | 
| Change From Baseline in the St George's Respiratory Questionnaire (SGRQ) Total Score at 12 and 24 Weeks | Absolute change from baseline in the St George's Respiratory Questionnaire (SGRQ) total score at 12 and 24 weeks. The SGRQ is a widely used disease specific questionnaire evaluating health related quality of life. The SGRQ Total Score is measured using patient self-reported question on disease impact on symptoms, patient activity, and daily life. SGRQ scores are calculated using weights attached to each item of the questionnaire which provides an estimate of the distress associated with the symptoms or state described in each item. The total score for SGRQ ranges from 0 to 100, with higher scores indicating more limitations. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Absolute Change From Baseline in The King's Brief Interstitial Lung Disease (KBILD) Questionnaire Total Score at 12 and 24 Weeks | Absolute change from baseline in The King's Brief Interstitial Lung Disease (KBILD) questionnaire total score at 12 and 24 weeks. The KBILD questionnaire is a disease specific questionnaire evaluating health related quality of life. The questionnaire consists of 15 items. Raw total scores were weighted with a Likert response scale to create the total score, total scores were transformed to a range of 0-100 ((actual score-lowest possible score/range)*100), with a score of 100 representing the best health status. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Change From Baseline in the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) Total Score at 12 and 24 Weeks | Change from baseline in the University of California, San Diego Shortness of Breath Questionnaire (UCSD-SOBQ) total score at 12 and 24 weeks. The UCSD-SOBQ is a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living, scores for each item range from 0 to 5, with higher scores indicating more limitations. Total score is calculated as the sum of all individual scores. Scores range from 0 to 120, with higher scores indicating more limitations. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Absolute Change From Baseline of Forced Vital Capacity (FVC) at 12 and 24 Weeks | Absolute change from baseline of forced vital capacity (FVC) at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Absolute Change From Baseline of Forced Vital Capacity (FVC) % Predicted at 12 and 24 Weeks | Absolute change from baseline of forced vital capacity (FVC) % predicted at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society (ATS) guideline on DLco measurements, and the prediction formula appropriate for that method. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Relative Change From Baseline of Forced Vital Capacity (FVC) at 12 and 24 Weeks | Relative change (unitless) from baseline of forced vital capacity (FVC) at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is measured in milliliter (mL). Its relative change from baseline at 12 (24) weeks is calculated as: (FVC measured at 12 (24) weeks - FVC measured at baseline)/ FVC measured at baseline *100%. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Relative Change From Baseline of Forced Vital Capacity (FVC) % Predicted at 12 and 24 Weeks | Relative change (unitless) from baseline of forced vital capacity (FVC) % predicted at 12 and 24 weeks. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society (ATS) guideline on DLco measurements, and the prediction formula appropriate for that method. The relative change from baseline of FVC % predicted at 12 (24) weeks is calculated as: (FVC % Predicted measured at 12 (24) weeks - FVC % Predicted measured at baseline)/ FVC % Predicted measured at baseline *100%. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Absolute Categorical Change of Forced Vital Capacity (FVC)% Predicted up to 12 and 24 Weeks (Decrease by >5%, Increase by >5%, and Change Within ≤5%) | Absolute categorical change of forced vital capacity (FVC)% predicted up to 12 and 24 weeks, the following three categories were defined: decrease by >5%, increase by >5%, and change within ≤5%. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society(ATS) guideline on DLco measurements, and the prediction formula appropriate for that method. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Absolute Categorical Change of Forced Vital Capacity (FVC)% Predicted up to 12 and 24 Weeks (Decrease by >10%, Increase by >10%, and Change Within ≤10%) | Absolute categorical change of forced vital capacity (FVC)% predicted up to 12 and 24 weeks, the following three categories were defined: decrease by >10%, increase by >10%, and change within ≤10%. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. For predicted normal values, different sites may use different prediction formulas, based on the method used to measure diffusing capacity of the lung for carbon monoxide (DLco). In any case, the method used must be in compliance with the European Respiratory Society (ERS)/American Thoracic Society(ATS) guideline on DLco measurements, and the prediction formula appropriate for that method. | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Change From Baseline in Daily Accelerometer Activity From Baseline at 12 and 24 Weeks: Score of Average Steps/Day | Change from baseline in daily accelerometer activity from baseline at 12 and 24 weeks: Score of average Steps/day. Categories were defined as follows: Steps (total daily value) 0 = 0 to 1900 steps/day = 1901 to 3700 steps/day = 3701 to 5500 steps/day = 5501 to 7300 steps/day = >7301 steps/day | Baseline (day 1), week 12 (day 85) and week 24 (day 169). | 
| Change From Baseline in Daily Accelerometer Activity From Baseline at 12 and 24 Weeks: Score of Average Vector Magnitude Units (VMU)/Day | Change from baseline in daily accelerometer activity from baseline at 12 and 24 weeks: Score of average vector magnitude units (VMU)/day. Categories were defined as follows: VMU (daily VMU/min) 0 = 0 to 50 VMU/min = 51 to 110 VMU/min = 111 to 190 VMU/min = 191 to 270 VMU/min = 271 to 440 VMU/min = >441 VMU/min | Baseline (day 1), week 12 (day 85) and week 24 (day 169). |