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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03099187




Registration number
NCT03099187
Ethics application status
Date submitted
31/03/2017
Date registered
4/04/2017
Date last updated
13/01/2021

Titles & IDs
Public title
A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease
Scientific title
Multicenter, International, Double-blind, Two-Arm, Randomized, Placebo-controlled Phase II Trial of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing ILD
Secondary ID [1] 0 0
2016-002744-17
Secondary ID [2] 0 0
MA39189
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Diseases, Interstitial 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

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

Experimental: Pirfenidone - Participants will receive pirfenidone 267 mg capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.

Experimental: Placebo - Participants will receive matching placebo capsule three times a day from Day 1 to 7 followed by 2 capsules three times a day from Day 8 to 14 then 3 capsules three times a day from Day 15 up to Week 24.


Treatment: Drugs: Pirfenidone
Pirfenidone 267 mg capsules three times in a day.

Treatment: Drugs: Placebo
Matching placebo capsules three times in a day.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
Timepoint [1] 0 0
Up to Week 24
Secondary outcome [1] 0 0
Change in Percent Predicted FVC
Timepoint [1] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [2] 0 0
Change in FVC
Timepoint [2] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [3] 0 0
Categorical Change in FVC of >5%
Timepoint [3] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [4] 0 0
Categorical Change in FVC of >10%
Timepoint [4] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [5] 0 0
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)
Timepoint [5] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [6] 0 0
Change in 6-minute Walk Distance (6MWD)
Timepoint [6] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [7] 0 0
Change in University of California, San Diego-Shortness of Breath Questionnaire Score
Timepoint [7] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [8] 0 0
Change in Score in Leicester Cough Questionnaire Score
Timepoint [8] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [9] 0 0
Change in Cough Visual Analog Scale (VAS) Score
Timepoint [9] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [10] 0 0
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ)
Timepoint [10] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [11] 0 0
Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause
Timepoint [11] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [12] 0 0
Percentage of Participants With Investigator-reported Acute Exacerbations
Timepoint [12] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [13] 0 0
Time to First Investigator-reported Acute Exacerbations
Timepoint [13] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [14] 0 0
Progression-free Survival (PFS)
Timepoint [14] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [15] 0 0
Progression-free Survival (PFS)
Timepoint [15] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [16] 0 0
Time to Death From Any Cause
Timepoint [16] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [17] 0 0
Time to Death From Respiratory Diseases
Timepoint [17] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [18] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Timepoint [18] 0 0
Baseline (Day 1) to Week 28
Secondary outcome [19] 0 0
Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period
Timepoint [19] 0 0
From administration of the first dose of study drug to Week 24
Secondary outcome [20] 0 0
Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up
Timepoint [20] 0 0
From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Secondary outcome [21] 0 0
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period
Timepoint [21] 0 0
Baseline (Day 1) to Week 24
Secondary outcome [22] 0 0
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up
Timepoint [22] 0 0
From the Follow-up Visit at Week 28 through the follow-up period of 12 Months

Eligibility
Key inclusion criteria
* Age >= 18-85 years
* Confirmed fibrosing ILD which, following multidisciplinary team review, cannot be classified with either high or moderate confidence as a specific idiopathic interstitial pneumonia or other defined ILD
* Progressive disease as considered by the investigator as participants deterioration within the last 6 months, which is defined as a rate of decline in forced vital capacity (FVC) >5% or a significant symptomatic worsening not due to cardiac, pulmonary vascular or other causes
* Extent of fibrosis >10% on high-resolution computed tomography
* Forced vital capacity >= 45% of predicted value
* Diffusing capacity of the lung for carbon monoxide (DLco) >= 30% of predicted value
* Forced expiratory volume in 1 second/FVC ratio >= 0.7
* Able to do 6-minute walk distance (6MWD) >= 150 meters
* For women of childbearing potential: agreement to remain abstinent or use a non-hormonal or hormonal contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of pirfenidone
* For men, agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Diagnosis with moderate or high confidence of nonspecific interstitial pneumonia and any ILD with an identifiable cause such as connective tissue disease-ILD, chronic hypersensitivity pneumonitis, or others
* Diagnosis of idiopathic pulmonary fibrosis independent of the confidence level
* History of unstable angina or myocardial infarction during the previous 6 months
* Treatment with high dose systemic corticosteroids, or any immunosuppressant other than mycophenolate mofetil/acid (MMF), at any time within the 4 weeks of the screening period. Participants being treated with MMF should be on a stable dose that is expected to remain stable throughout the trial and was started at least 3 months prior to screening
* Participants previously treated with pirfenidone or nintedanib
* Participants treated with N-acetyl-cysteine for fibrotic lung disease, at any time within the 4 weeks of the screening period
* Drug treatment for any type of pulmonary hypertension
* Participation in a trial of an investigational medicinal product within the last 4 weeks
* Significant other organ co-morbidity including hepatic or renal impairment
* Predicted life expectancy < 12 months or on an active transplant waiting list
* Use of any tobacco product in the 12 weeks prior to the start of screening, or any unwillingness to abstain from their use through to the Follow-up Visit
* Illicit drug or alcohol abuse within 12 months prior to screening
* Planned major surgery during the trial
* Hypersensitivity to the active substance or to any of the excipients of pirfenidone
* History of angioedema
* Concomitant use of fluvoxamine
* Clinical evidence of any active infection
* Any history of hepatic impairment, elevation of transaminase enzymes, or liver function test results as: Total bilirubin above the upper limit of normal (ULN), Aspartate aminotransferase or alanine aminotransferase >1.5 × ULN, and Alkaline phosphatase >2.0 × ULN
* Creatinine clearance < 30 milliliter (mL) per minute, calculated using the Cockcroft-Gault formula
* Any serious medical condition, clinically significant abnormality on an Electrocardiogram (ECG) at screening, or laboratory test results
* An ECG with a heart rate corrected QT interval using Fridericia's formula as >= 500 milliseconds at screening, or a family or personal history of long QT syndrome

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 2
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
15/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/01/2020
Sample size
Target
Accrual to date
Final
253
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
John Hunter Hospital; Respiratory Department; Respiratory Department - New Lambton Heights
Recruitment hospital [3] 0 0
Lung Research Queensland - Nundah
Recruitment hospital [4] 0 0
Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine - Woolloongabba
Recruitment hospital [5] 0 0
Royal Adelaide Hospital; Respiratory Clinical Trials Unit, Thoracic Medicine - Adelaide
Recruitment hospital [6] 0 0
Respiratory Department - Heidelberg
Recruitment hospital [7] 0 0
The Alfred Hospital - Prahan
Recruitment hospital [8] 0 0
Fiona Stanley Hospital; Advanced Lung Disease Unit - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
4101 - Nundah
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3181 - Prahan
Recruitment postcode(s) [8] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Canada
State/province [4] 0 0
British Columbia
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Jihlava
Country [8] 0 0
Czechia
State/province [8] 0 0
Olomouc
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha 2
Country [10] 0 0
Denmark
State/province [10] 0 0
Aarhus N
Country [11] 0 0
Denmark
State/province [11] 0 0
Hellerup
Country [12] 0 0
Denmark
State/province [12] 0 0
Odense C
Country [13] 0 0
Germany
State/province [13] 0 0
Bad Berka
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Germany
State/province [15] 0 0
Gießen
Country [16] 0 0
Germany
State/province [16] 0 0
Heidelberg
Country [17] 0 0
Germany
State/province [17] 0 0
München
Country [18] 0 0
Greece
State/province [18] 0 0
Athens
Country [19] 0 0
Greece
State/province [19] 0 0
Chaidari
Country [20] 0 0
Greece
State/province [20] 0 0
Heraklio
Country [21] 0 0
Ireland
State/province [21] 0 0
Dublin
Country [22] 0 0
Israel
State/province [22] 0 0
Beer Sheba
Country [23] 0 0
Israel
State/province [23] 0 0
Haifa
Country [24] 0 0
Israel
State/province [24] 0 0
Jerusalem
Country [25] 0 0
Israel
State/province [25] 0 0
Kfar Saba
Country [26] 0 0
Israel
State/province [26] 0 0
Petach Tikva
Country [27] 0 0
Israel
State/province [27] 0 0
Rehovot
Country [28] 0 0
Italy
State/province [28] 0 0
Emilia-Romagna
Country [29] 0 0
Italy
State/province [29] 0 0
Lombardia
Country [30] 0 0
Italy
State/province [30] 0 0
Marche
Country [31] 0 0
Italy
State/province [31] 0 0
Piemonte
Country [32] 0 0
Italy
State/province [32] 0 0
Toscana
Country [33] 0 0
Poland
State/province [33] 0 0
Gdansk
Country [34] 0 0
Poland
State/province [34] 0 0
Lodz
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa
Country [36] 0 0
Portugal
State/province [36] 0 0
Aveiro
Country [37] 0 0
Portugal
State/province [37] 0 0
Coimbra
Country [38] 0 0
Portugal
State/province [38] 0 0
Porto
Country [39] 0 0
Portugal
State/province [39] 0 0
Vila Nova De Gaia
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Cantabria
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Birmingham
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Bristol
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cambridge
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Edinburgh
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Exeter
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Leicester
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Manchester
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Sheffield
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Southampton
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Stoke on Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy and safety of pirfenidone in participants with fibrosing interstitial lung disease (ILD) who cannot be classified with moderate or high confidence into any other category of fibrosing ILD by multidisciplinary team (MDT) review ("unclassifiable" ILD).
Trial website
https://clinicaltrials.gov/study/NCT03099187
Trial related presentations / publications
Molina-Molina M, Kreuter M, Cottin V, Corte TJ, Gilberg F, Kirchgaessler KU, Axmann J, Maher TM. Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. Front Med (Lausanne). 2022 Jun 17;9:897102. doi: 10.3389/fmed.2022.897102. eCollection 2022.
Kreuter M, Maher TM, Corte TJ, Molina-Molina M, Axmann J, Gilberg F, Kirchgaessler KU, Cottin V. Pirfenidone in Unclassifiable Interstitial Lung Disease: A Subgroup Analysis by Concomitant Mycophenolate Mofetil and/or Previous Corticosteroid Use. Adv Ther. 2022 Feb;39(2):1081-1095. doi: 10.1007/s12325-021-02009-w. Epub 2021 Dec 22.
Maher TM, Corte TJ, Fischer A, Kreuter M, Lederer DJ, Molina-Molina M, Axmann J, Kirchgaessler KU, Samara K, Gilberg F, Cottin V. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2020 Feb;8(2):147-157. doi: 10.1016/S2213-2600(19)30341-8. Epub 2019 Sep 29.
Graney BA, Fischer A. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc. 2019 May;16(5):525-533. doi: 10.1513/AnnalsATS.201808-565CME.
Maher TM, Corte TJ, Fischer A, Kreuter M, Lederer DJ, Molina-Molina M, Axmann J, Kirchgaessler KU, Cottin V. Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: design of a double-blind, randomised, placebo-controlled phase II trial. BMJ Open Respir Res. 2018 Sep 4;5(1):e000289. doi: 10.1136/bmjresp-2018-000289. eCollection 2018.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03099187