Lung Diseases, InterstitialPhase 2NCT03099187
A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease
A Phase 2 study testing Pirfenidone in people with Lung Diseases, Interstitial, run by Hoffmann-La Roche at 66 sites in 14 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Lung Diseases, Interstitial
- What is being tested?
- Pirfenidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 253 participants
- Where
- 66 sitesin 14 countries
- Study dates
- 15 May 2017to 10 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
66 sites in 14 countries.
66 sites in 14 countries
United Kingdom12 sites
University Hospital Birmingham Queen Elizabeth Hospital
Birmingham, B17 0NH
Southmead Hospital; Respiratory Department
Bristol, BS10-5NB
Papworth Hospital NHS Foundation Trust; Respiratory Department
Cambridge, CB23 3RE
Edinburgh Royal Infirmary; Respiratory Department
Edinburgh, EH16 4SA
Royal Devon and Exeter Hospital (Wonford)
Exeter, EX2 5DW
Glenfield Hospital
Leicester, LE3 9QP
University College London Hospital; Respiratory Medicine
London, NW1 2BU
Royal Brompton Hospital; Respiratory Department
London, SW3 6NP
Wythenshawe Hospital; North West Lung Research Centre
Manchester, M23 9LT
Northern General Hospital
Sheffield, S5 7AU
Southampton University Hospitals NHS Trust
Southampton, SO16 6YD
Royal Stoke University Hospital
Stoke-on-Trent, ST4 6QG
Australia8 sites
Royal Adelaide Hospital; Respiratory Clinical Trials Unit, Thoracic Medicine
Adelaide, South Australia, 5000
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Respiratory Department
Heidelberg, Victoria, 3084
Fiona Stanley Hospital; Advanced Lung Disease Unit
Murdoch, Western Australia, 6150
John Hunter Hospital; Respiratory Department; Respiratory Department
New Lambton Heights, New South Wales, 2305
Lung Research Queensland
Nundah, Queensland, 4101
The Alfred Hospital
Prahan, Victoria, 3181
Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine
Woolloongabba, Queensland, 4102
Israel7 sites
Soroka; Pulmonary Clinic
Beersheba, 8410101
Carmel Medical Center; Pulmonary Institute
Haifa, 3436212
Shaare Zedek Medical Center; Pulmonary Inst.
Jerusalem, 9103102
Hadassah Medical Center; Pulmonary Institute
Jerusalem, 9112001
Meir Medical Center; Pulmonary Dept
Kfar Saba, 4428164
Beilinson Medical Center; Pulmonary Inst.
Petah Tikva, 4941492
Kaplan Medical Center
Rehovot, 7610001
Germany5 sites
Zentralklinik Bad Berka GmbH; Pneumologie
Bad Berka, 99437
Evang. Lungenklinik Berlin Klinik für Pneumologie
Berlin, 13125
Klinik der Justus-Liebig-Universität; Innere Medizin
Giessen, 35392
Thoraxklinik Heidelberg gGmbH
Heidelberg, 69126
Klinikum der Universität München; Campus Großhadern; Med. Klinik und Poliklinik V
München, 81377
Italy5 sites
Azienda Ospedaliero-Universitaria Careggi; SOD Pneumologia e Fisiopatologia Toracico Polmonare
Florence, Tuscany, 50134
Ospedale Morgagni-Pierantoni; U.O. Pneumologia
Forlì, Emilia-Romagna, 47121
Ospedale San Giuseppe; U.O. di Pneumologia
Milan, Lombardy, 20123
A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone
Orbassano (TO), Piedmont, 10043
A.O.U. Ospedali Riuniti Umberto I -G.M. Lancisi-G. Salesi Ancona; SOD Pneumologia
Torrette Di Ancona, The Marches, 60100
Spain5 sites
Hospital Universitari de Bellvitge ; Servicio de Neumologia
L'Hospitalet de Llobregat, Barcelona, 08097
Hospital Universitario La Princesa; Servicio de Neumologia
Madrid, 28006
Hospital Clínico San Carlos - Servicio de Neumologia
Madrid, 28040
Hospital Universitario 12 de Octubre; Servicio de Neumologia
Madrid, 28041
Hospital Universitario Marques de Valdecilla; Servicio de neumologia
Santander, Cantabria, 39008
Czechia4 sites
Fakultni Nemocnice Brno-Bohunice; Klinika Tuberkulozy A Respiracnich Chorob
Brno, 639 00
Nemocnice Jihlava
Jihlava, 58633
Fakultni nemocnice Olomouc; Pneumologicka klinika
Olomouc, 775 20
Vseobecna fakultni nemocnice v Praze; I. klinika tuberkulozy a respiracnich nemoci
Prague, 128 08
Portugal4 sites
Hospital Infante D. Pedro; Servico de Pneumologia
Aveiro, 3814-501
HUC; Servico de Pneumologia A
Coimbra, 3000-075
Hospital de Sao Joao; Servico de Pneumologia
Porto, 4200
CHVNG/E_Unidade 1; Servico de Pneumologia
Vila Nova de Gaia, 4434-502
Belgium3 sites
ULB Hôpital Erasme
Brussels, 1070
Cliniques Universitaires St-Luc
Brussels, 1200
UZ Leuven Gasthuisberg
Leuven, 3000
Denmark3 sites
Aarhus Universitetshospital; Lungesygdomme, Forskning
Aarhus N, 8200
Gentofte Hospital, Lungemedicinsk Afdeling
Hellerup, 2900
Odense Universitetshospital, Lungemedicinsk Afdeling J
Odense C, 5000
Greece3 sites
Sotiria Hospital for Diseases of the Chest, Academic Department of Pneumonology
Athens, 115 27
University General Hospital of Athens "Attikon", B' University Pulmonary Clinic
Chaïdári, 124 62
University General Hospital of Heraklio, Pulmonary Clinic
Heraklio, 711 10
Poland3 sites
Uniwersyteckie Centrum Kliniczne;Klinika Alergologii i Pneumonologii
Gdansk, 80-214
Uniwersytecki Szpital Kliniczny Nr 1 im.N.Barlickiego Oddzial Kliniczny Pneumonologii i Alergologii
Lodz, 90-153
Instytut Gruźlicy i Chorób Płuc, I Klinika Chorób Płuc
Warsaw, 01-138
Canada2 sites
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N4A6
Pacifica Lung Research Center/St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
Ireland2 sites
Mater Misericordiae University hospital
Dublin, 7
St Vincents University Hospital
Dublin
About this study
Official title: Multicenter, International, Double-blind, Two-Arm, Randomized, Placebo-controlled Phase II Trial of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing ILD
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).
Read the detailed description
Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone versus placebo will be assessed by daily measurement of forced vital capacity using a handheld spirometer over the treatment period. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without interstitial pneumonia with autoimmune features (IPAF). All study participants who attend the follow-up visit at Week 28 will be offered the opportunity to receive open-label pirfenidone within the trial protocol. In order to maintain blinding of the controlled period of the study, all study participants will discontinue treatment by Week 24 and return for a follow-up visit 4 weeks later. Study participants eligible to participate in the single-arm 12-month extension will be initiated on open-label pirfenidone during this visit (re-starting the dose titration from one capsule three times daily [TID]). During the long-term extension period, study participants will be monitored for safety, initially at monthly visits during the first 6 months and thereafter approximately every 3 months. A final follow-up visit will take place 4 weeks after the last dose of pirfenidone is taken.
- Conditions
- Lung Diseases, Interstitial
- Being tested
- Pirfenidone, Placebo
- Medical subject headings
- Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirfenidoneDrug
Pirfenidone 267 mg capsules three times in a day.
PlaceboDrug
Matching placebo capsules three times in a day.
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone | Experimental | 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. Receives: Drug: Pirfenidone |
| Placebo | Experimental | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
Rate of decline in FVC was measured in mL by daily handheld spirometer. The analyses were repeated due to an additional independent review of the home spirometry data.
Measured: Up to Week 24
Secondary outcomes (22)
Change in Percent Predicted FVC
FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Measured: Baseline (Day 1) to Week 24
Change in FVC
FVC was measured in liter (L) by spirometry. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Measured: Baseline (Day 1) to Week 24
Categorical Change in FVC of >5%
Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Measured: Baseline (Day 1) to Week 24
Categorical Change in FVC of >10%
Categorical change in FVC was measured both by daily spirometry as well as by spirometry during clinical visits. Only the site spirometry data were used as the daily spirometry data were not normally distributed. The analyses were repeated due to additional data cleaning activities that were not conducted during the primary analysis.
Measured: Baseline (Day 1) to Week 24
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)
The DLco is a pulmonary function test that measures the capacity for the lung to carry out gas exchange between the inhaled breath and the pulmonary capillary blood vessels and the DLco %-predicted represents the DLco expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity.
Measured: Baseline (Day 1) to Week 24
Change in 6-minute Walk Distance (6MWD)
Comparison of 6-minute walk distance before beginning and after completing study therapy.
Measured: Baseline (Day 1) to Week 24
Change in University of California, San Diego-Shortness of Breath Questionnaire Score
University of California, San Diego Shortness of Breath Questionnaire (SOBQ) consists of 24-item on a scale of 0 to 5 with 0=not at all and 5=maximal or unable to do because of breathlessness. The total scores were calculated by summation of the 24 items scores and transformed into 0-100, with 0= poor quality of life , and 100= excellent quality of life.
Measured: Baseline (Day 1) to Week 24
Change in Score in Leicester Cough Questionnaire Score
The Leicester Cough Questionnaire is a patient-reported questionnaire evaluating the impact of cough on quality of life. The questionnaire comprises 19 items. Each item assesses symptoms, or the impact of symptoms, over the last 2 weeks on a seven-point Likert scale. Scores in three domains (physical, psychological and social) were calculated as a mean for each domain (range 1 to 7). A total score (range 3 to 21) was also calculated by adding the domain scores together. Higher scores indicate better quality of life.
Measured: Baseline (Day 1) to Week 24
Change in Cough Visual Analog Scale (VAS) Score
Cough VAS are 100-mm linear scales on which participants indicate the severity of their cough; 0 mm represents no cough and 100 mm the worst cough ever.
Measured: Baseline (Day 1) to Week 24
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ)
The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in participants with diseases of airways obstruction. Three component scores are: Symptoms (respiratory symptoms and severity); Activity (activities that cause or are limited by breathlessness); Impacts (social functioning and psychological disturbances due to airway disease). Each component sub-scores are calculated from the summed weights for the positive responses to questions. Total score summaries the impact of disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. It is calculated by summing all positive responses in the questionnaire and expressing the result as a percentage of the total weight for the questionnaire.
Measured: Baseline (Day 1) to Week 24
Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause
Participants with non-elective hospitalization are reported.
Measured: Baseline (Day 1) to Week 24
Percentage of Participants With Investigator-reported Acute Exacerbations
Percentage of participants with acute exacerbation arereported.
Measured: Baseline (Day 1) to Week 24
Time to First Investigator-reported Acute Exacerbations
Time to first investigator reported acute exacerbations from start of treatment are reported.
Measured: Baseline (Day 1) to Week 24
Progression-free Survival (PFS)
PFS is defined as the time to the first occurrence of a >10% absolute decline in percent predicted FVC, a >50 m decline of 6MWD, or death.
Measured: Baseline (Day 1) to Week 24
Progression-free Survival (PFS)
PFS is defined as the time to the first occurrence of a >10% relative decline in percent predicted FVC, non-elective respiratory hospitalization, or death.
Measured: Baseline (Day 1) to Week 24
Time to Death From Any Cause
Time to first documented death from start of treatment is reported.
Measured: Baseline (Day 1) to Week 24
Time to Death From Respiratory Diseases
Time to first documented death due to respiratory diseases from start of treatment will be reported.
Measured: Baseline (Day 1) to Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Measured: Baseline (Day 1) to Week 28
Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period
Number of participants with dose reduction and treatment interruptions are reported.
Measured: From administration of the first dose of study drug to Week 24
Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up
Number of participants with dose reduction and treatment interruptions are reported.
Measured: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period
Number of participants withdrawn from trial treatment or trial discontinuations are reported.
Measured: Baseline (Day 1) to Week 24
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up
Number of participants withdrawn from trial treatment or trial discontinuations are reported.
Measured: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start15 May 2017
- Primary completion21 Nov 2018
- Study completion10 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Lung Diseases, InterstitialStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 253 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03099187
- Sponsor's protocol ID
- MA39189
- Other IDs
- 2016-002744-17, 2016
- Status last verified
- Dec 2020
- First submitted
- 31 Mar 2017
- Last updated
- 13 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 35783648Kreuter 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.
PubMed 34936057Maher 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.
PubMed 31578169Graney BA, Fischer A. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc. 2019 May;16(5):525-533. doi: 10.1513/AnnalsATS.201808-565CME.
PubMed 30695649Maher 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.
PubMed 30233802
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, International, Double-blind, Two-Arm, Randomized, Placebo-controlled Phase II Trial of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing ILD
- ClinicalTrials.gov ID
- NCT03099187
- Acronym / sponsor ID
- MA39189
- Conditions
- Lung Diseases, Interstitial
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 253 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 15 May 2017 (actual)
- Primary completion
- 21 Nov 2018 (actual)
- Study completion
- 10 Jan 2020 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 3 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Study participants will be randomised to receive 801 mg pirfenidone or placebo three times daily for 24 weeks. The efficacy of pirfenidone versus placebo will be assessed by daily measurement of forced vital capacity using a handheld spirometer over the treatment period. Additionally, the study will assess the efficacy and safety of pirfenidone with and without concomitant mycophenolate mofetil treatment and in study participants with or without interstitial pneumonia with autoimmune features (IPAF). All study participants who attend the follow-up visit at Week 28 will be offered the opportunity to receive open-label pirfenidone within the trial protocol. In order to maintain blinding of the controlled period of the study, all study participants will discontinue treatment by Week 24 and return for a follow-up visit 4 weeks later. Study participants eligible to participate in the single-arm 12-month extension will be initiated on open-label pirfenidone during this visit (re-starting the dose titration from one capsule three times daily [TID]). During the long-term extension period, study participants will be monitored for safety, initially at monthly visits during the first 6 months and thereafter approximately every 3 months. A final follow-up visit will take place 4 weeks after the last dose of pirfenidone is taken.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone | Experimental | Drug: PirfenidoneParticipants 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. |
| Placebo | Experimental | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PirfenidonePirfenidone 267 mg capsules three times in a day. | Drug | Pirfenidone |
| PlaceboMatching placebo capsules three times in a day. | Drug | Placebo |
Primary outcome
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period
Time frame: Up to Week 24
Rate of decline in FVC was measured in mL by daily handheld spirometer. The analyses were repeated due to an additional independent review of the home spirometry data.
22 secondary outcomes
Change in Percent Predicted FVC
Time frame: Baseline (Day 1) to Week 24
Change in FVC
Time frame: Baseline (Day 1) to Week 24
Categorical Change in FVC of >5%
Time frame: Baseline (Day 1) to Week 24
Categorical Change in FVC of >10%
Time frame: Baseline (Day 1) to Week 24
Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)
Time frame: Baseline (Day 1) to Week 24
Change in 6-minute Walk Distance (6MWD)
Time frame: Baseline (Day 1) to Week 24
Change in University of California, San Diego-Shortness of Breath Questionnaire Score
Time frame: Baseline (Day 1) to Week 24
Change in Score in Leicester Cough Questionnaire Score
Time frame: Baseline (Day 1) to Week 24
Change in Cough Visual Analog Scale (VAS) Score
Time frame: Baseline (Day 1) to Week 24
Change in Total and Sub-scores of the Saint George's Respiratory Questionnaire (SGRQ)
Time frame: Baseline (Day 1) to Week 24
Number of Participants With Non-elective Hospitalization, Both Respiratory and All Cause
Time frame: Baseline (Day 1) to Week 24
Percentage of Participants With Investigator-reported Acute Exacerbations
Time frame: Baseline (Day 1) to Week 24
Time to First Investigator-reported Acute Exacerbations
Time frame: Baseline (Day 1) to Week 24
Progression-free Survival (PFS)
Time frame: Baseline (Day 1) to Week 24
Progression-free Survival (PFS)
Time frame: Baseline (Day 1) to Week 24
Time to Death From Any Cause
Time frame: Baseline (Day 1) to Week 24
Time to Death From Respiratory Diseases
Time frame: Baseline (Day 1) to Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline (Day 1) to Week 28
Number of Participants With Dose Reductions and Treatment Interruptions During the Double-Blind Period
Time frame: From administration of the first dose of study drug to Week 24
Number of Participants With Dose Reductions and Treatment Interruptions During the 12-month Safety Follow-up
Time frame: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the Double-Blind Period
Time frame: Baseline (Day 1) to Week 24
Number of Participants Withdrawn From Trial Treatment or Trial Discontinuations During the 12-month Safety Follow-up
Time frame: From the Follow-up Visit at Week 28 through the follow-up period of 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35783648Molina-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.
- Derived from this study: PubMed 34936057Kreuter 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.
- Derived from this study: PubMed 31578169Maher 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.
- Derived from this study: PubMed 30695649Graney BA, Fischer A. Interstitial Pneumonia with Autoimmune Features. Ann Am Thorac Soc. 2019 May;16(5):525-533. doi: 10.1513/AnnalsATS.201808-565CME.
- Derived from this study: PubMed 30233802Maher 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
66 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pirfenidone in people with Lung Diseases, Interstitial, run by Hoffmann-La Roche at 66 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 66 sites in United Kingdom, Australia, Israel, Germany, Italy and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Decline in Forced Vital Capacity (FVC) Over the 24-week Double-blind Treatment Period (time frame: Up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03099187, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2021.