A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing Interstitial Lung Disease

NCT03099187 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MA391892016-002744-17
• Study Type: interventional
• Target: 253
• Locations: 14 countries
• Sites: 66

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).

Conditions

Lung Diseases, Interstitial

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to Week 24

Secondary Outcomes (22)

• Change in Percent Predicted FVC

  Baseline (Day 1) to Week 24

• Change in FVC

  Baseline (Day 1) to Week 24

• Categorical Change in FVC of >5%

  Baseline (Day 1) to Week 24

• Categorical Change in FVC of >10%

  Baseline (Day 1) to Week 24

• Change in Percent Predicted Diffusing Capacity of the Lung for Carbon Monoxide (DLco)

  Baseline (Day 1) to Week 24

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Pirfenidone DRUG

Pirfenidone 267 mg capsules three times in a day.

Pirfenidone

Placebo DRUG

Matching placebo capsules three times in a day.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (66)

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

John Hunter Hospital; Respiratory Department; Respiratory Department

New Lambton Heights, New South Wales, 2305, Australia

Location

Lung Research Queensland

Nundah, Queensland, 4101, Australia

Location

Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital; Respiratory Clinical Trials Unit, Thoracic Medicine

Adelaide, South Australia, 5000, Australia

Location

Respiratory Department

Heidelberg, Victoria, 3084, Australia

Location

The Alfred Hospital

Prahan, Victoria, 3181, Australia

Location

Fiona Stanley Hospital; Advanced Lung Disease Unit

Murdoch, Western Australia, 6150, Australia

Location

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Pacifica Lung Research Center/St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N4A6, Canada

Location

Fakultni Nemocnice Brno-Bohunice; Klinika Tuberkulozy A Respiracnich Chorob

Brno, 639 00, Czechia

Location

Nemocnice Jihlava

Jihlava, 58633, Czechia

Location

Fakultni nemocnice Olomouc; Pneumologicka klinika

Olomouc, 775 20, Czechia

Location

Vseobecna fakultni nemocnice v Praze; I. klinika tuberkulozy a respiracnich nemoci

Prague, 128 08, Czechia

Location

Aarhus Universitetshospital; Lungesygdomme, Forskning

Aarhus N, 8200, Denmark

Location

Gentofte Hospital, Lungemedicinsk Afdeling

Hellerup, 2900, Denmark

Location

Odense Universitetshospital, Lungemedicinsk Afdeling J

Odense C, 5000, Denmark

Location

Zentralklinik Bad Berka GmbH; Pneumologie

Bad Berka, 99437, Germany

Location

Evang. Lungenklinik Berlin Klinik für Pneumologie

Berlin, 13125, Germany

Location

Klinik der Justus-Liebig-Universität; Innere Medizin

Giessen, 35392, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

Location

Klinikum der Universität München; Campus Großhadern; Med. Klinik und Poliklinik V

München, 81377, Germany

Location

Sotiria Hospital for Diseases of the Chest, Academic Department of Pneumonology

Athens, 115 27, Greece

Location

University General Hospital of Athens "Attikon", B' University Pulmonary Clinic

Chaïdári, 124 62, Greece

Location

University General Hospital of Heraklio, Pulmonary Clinic

Heraklio, 711 10, Greece

Location

Mater Misericordiae University hospital

Dublin, 7, Ireland

Location

St Vincents University Hospital

Dublin, Ireland

Location

Soroka; Pulmonary Clinic

Beersheba, 8410101, Israel

Location

Carmel Medical Center; Pulmonary Institute

Haifa, 3436212, Israel

Location

Shaare Zedek Medical Center; Pulmonary Inst.

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center; Pulmonary Institute

Jerusalem, 9112001, Israel

Location

Meir Medical Center; Pulmonary Dept

Kfar Saba, 4428164, Israel

Location

Beilinson Medical Center; Pulmonary Inst.

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center

Rehovot, 7610001, Israel

Location

Ospedale Morgagni-Pierantoni; U.O. Pneumologia

Forlì, Emilia-Romagna, 47121, Italy

Location

Ospedale San Giuseppe; U.O. di Pneumologia

Milan, Lombardy, 20123, Italy

Location

A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone

Orbassano (TO), Piedmont, 10043, Italy

Location

A.O.U. Ospedali Riuniti Umberto I -G.M. Lancisi-G. Salesi Ancona; SOD Pneumologia

Torrette Di Ancona, The Marches, 60100, Italy

Location

Azienda Ospedaliero-Universitaria Careggi; SOD Pneumologia e Fisiopatologia Toracico Polmonare

Florence, Tuscany, 50134, Italy

Location

Uniwersyteckie Centrum Kliniczne;Klinika Alergologii i Pneumonologii

Gdansk, 80-214, Poland

Location

Uniwersytecki Szpital Kliniczny Nr 1 im.N.Barlickiego Oddzial Kliniczny Pneumonologii i Alergologii

Lodz, 90-153, Poland

Location

Instytut Gruźlicy i Chorób Płuc, I Klinika Chorób Płuc

Warsaw, 01-138, Poland

Location

Hospital Infante D. Pedro; Servico de Pneumologia

Aveiro, 3814-501, Portugal

Location

HUC; Servico de Pneumologia A

Coimbra, 3000-075, Portugal

Location

Hospital de Sao Joao; Servico de Pneumologia

Porto, 4200, Portugal

Location

CHVNG/E_Unidade 1; Servico de Pneumologia

Vila Nova de Gaia, 4434-502, Portugal

Location

Hospital Universitari de Bellvitge ; Servicio de Neumologia

L'Hospitalet de Llobregat, Barcelona, 08097, Spain

Location

Hospital Universitario Marques de Valdecilla; Servicio de neumologia

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario La Princesa; Servicio de Neumologia

Madrid, 28006, Spain

Location

Hospital Clínico San Carlos - Servicio de Neumologia

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Neumologia

Madrid, 28041, Spain

Location

University Hospital Birmingham Queen Elizabeth Hospital

Birmingham, B17 0NH, United Kingdom

Location

Southmead Hospital; Respiratory Department

Bristol, BS10-5NB, United Kingdom

Location

Papworth Hospital NHS Foundation Trust; Respiratory Department

Cambridge, CB23 3RE, United Kingdom

Location

Edinburgh Royal Infirmary; Respiratory Department

Edinburgh, EH16 4SA, United Kingdom

Location

Royal Devon and Exeter Hospital (Wonford)

Exeter, EX2 5DW, United Kingdom

Location

Glenfield Hospital

Leicester, LE3 9QP, United Kingdom

Location

University College London Hospital; Respiratory Medicine

London, NW1 2BU, United Kingdom

Location

Royal Brompton Hospital; Respiratory Department

London, SW3 6NP, United Kingdom

Location

Wythenshawe Hospital; North West Lung Research Centre

Manchester, M23 9LT, United Kingdom

Location

Northern General Hospital

Sheffield, S5 7AU, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 35783648 DERIVED

• 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.

  PMID: 34936057 DERIVED

• 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.

  PMID: 31578169 DERIVED

• 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.

  PMID: 30695649 DERIVED

• 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.

  PMID: 30233802 DERIVED

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 4, 2017
• Study Start: May 15, 2017
• Primary Completion: November 21, 2018
• Study Completion: January 10, 2020
• Last Updated: January 13, 2021
• Results First Posted: January 3, 2020

Record last verified: 2020-12

Locations

CA (2); AU (8); DK (3); DE (5); IE (2); GB (12); GR (3); BE (3); PL (3); PT (4); IL (7); CZ (4); IT (5); ES (5)