Efficacy, Safety, and Tolerability Study of Pirfenidone in Combination With Sildenafil in Participants With Advanced Idiopathic Pulmonary Fibrosis (IPF) and Intermediate or High Probability of Group 3 Pulmonary Hypertension

NCT02951429 | Completed Phase 2 Results

• 2 other identifiers: MA299572015-005131-40
• Study Type: interventional
• Target: 177
• Locations: 13 countries
• Sites: 56

Brief Summary

This Phase IIb, randomized, placebo-controlled, multicenter, international study will evaluate the efficacy, safety, and tolerability of sildenafil or placebo added to pirfenidone (Esbriet) treatment in participants with advanced IPF and intermediate or high probability of Group 3 pulmonary hypertension (PH) who are on a stable dose of pirfenidone with demonstrated tolerability. Participants will be randomized to receive 1 year of treatment with either oral sildenafil or matching placebo while continuing to take pirfenidone.

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause

  Disease Progression defined as relative decline in 6-minute walking distance (6MWD) from baseline (defined as \>25% from baseline or 15-25% from baseline associated with worsening oxygen saturation, worsening Borg score, or increased oxygen requirements), respiratory-related non-elective hospitalizations, or all-cause mortality.

  Baseline up to Week 52

Secondary Outcomes (26)

• Time to First Occurrence of Disease Progression

  Baseline up to Week 52

• Time to Multiple Occurrence of Disease Progression Events

  Baseline up to Week 52

• Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15%

  Baseline up to Week 52

• Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD)

  Baseline up to Week 52

• Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52

  Baseline up to Week 52

Study Arms (2)

Pirfenidone + Placebo

PLACEBO COMPARATOR

Participants will receive pirfenidone along with placebo matched to sildenafil, orally, three times a day (TID) for 52 weeks.

Drug: Pirfenidone; Drug: Placebo

Pirfenidone + Sildenafil

EXPERIMENTAL

Participants will receive pirfenidone along with sildenafil, orally, TID for 52 weeks.

Drug: Pirfenidone; Drug: Sildenafil

Interventions

Pirfenidone DRUG

Pirfenidone will be given in the range of 1602 to 2403 milligram per day (mg/day), as 3 divided doses.

Also known as: Esbriet, RO0220912

Pirfenidone + Placebo; Pirfenidone + Sildenafil

Placebo DRUG

Placebo matched with sildenafil.

Pirfenidone + Placebo

Sildenafil DRUG

Sildenafil will be given as 20 mg, TID.

Also known as: RO0280296

Pirfenidone + Sildenafil

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of IPF for at least 3 months prior to Screening
• Confirmation of IPF diagnosis by the investigator in accordance with the 2011 international consensus guidelines at screening
• Advanced IPF (defined as a measurable carbon monoxide diffusing capacity \[DLCO\] less than or equal to (\<=)40% of predicted value at Screening) and intermediate or high probability of group 3 pulmonary hypertension (PH)
• Participants receiving pirfenidone for at least 12 weeks, at a dose in the range of 1602 to 2403 mg/day for at least 4 weeks prior to Screening and must not have experienced either a new or ongoing adverse event of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.03) Grade 2 or higher and considered by the investigator to be related to pirfenidone, or an interruption of pirfenidone treatment of greater than (\>)7 days for any reason
• WHO Functional Class II or III at Screening
• MWD of 100 to 450 meters at screening
• Women of childbearing potential and for men who are not surgically sterile agreement to remain abstinent or use of contraceptive measures

You may not qualify if:

• History of any of the following types of PH: Group 1 (PAH); Group 1 (pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis); Group 2 (left-heart disease); Group 3 (due to conditions other than interstitial lung disease, including chronic obstructive pulmonary disease \[COPD\], sleep-disordered breathing, alveolar hypoventilation, high altitude, or developmental abnormalities); Group 4 (chronic thromboembolic pulmonary hypertension); Group 5 (other disorders)
• History of clinically significant cardiac disease
• History of coexistent and clinically significant COPD, bronchiectasis, asthma, inadequately treated sleep-disordered breathing, or any clinically significant pulmonary diseases or disorders other than IPF or PH secondary to IPF
• History of use of drugs and toxins known to cause PAH, including aminorex, fenfluramine, dexenfluramine, and amphetamines
• FEV1/FVC ratio less than (\<) 0.70 post bronchodilator; SpO2 saturation at rest \<92% with \>= 6 liters (L) of supplemental oxygen at Screening
• Extent of emphysema greater than the extent of fibrotic changes (honeycombing and reticular changes) on any previous high-resolution computed tomography (HRCT) scan, in the opinion of the Investigator
• Smoked tobacco within 3 months prior to screening or is unwilling to avoid tobacco products (cigarettes, pipe, cigars) throughout the study
• Illicit drug or significant alcohol abuse
• Electrocardiogram (ECG) with a heart-rate corrected QT interval (corrected using Fridericia's formula \[QTcF\]) \>=500 milliseconds (ms) at screening, or a family or personal history of long QT syndrome

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (56)

ULB Hôpital Erasme

Brussels, 1070, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

CHU Sart-Tilman

Liège, 4000, Belgium

Location

CHU UCL Mont-Godinne

Mont-godinne, 5530, Belgium

Location

Hotel Dieu Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

CHUM Hôpital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval)

Ste. Foy, Quebec, G1V 4G5, Canada

Location

Thomayerova nemocnice; Pneumologicka klinika 1.LF UK TN

Praha 4 - Krc, 140 59, Czechia

Location

Clinical Research Center (CRC), Faculty of Medicine, Alexandria University

Alexandria, 21131, Egypt

Location

Kasr El-Aini-Chest Unit; Department 3-Chest Unit

Cairo, 11562, Egypt

Location

Ain Shams University Hospital-Chest unit; Chest unit

Cairo, 11566, Egypt

Location

Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie

Coswig, 01640, Germany

Location

Klinik Donaustauf Zentrum für Pneumologie

Donaustauf, 93093, Germany

Location

Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie

Essen, 45239, Germany

Location

Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda

Fulda, 36043, Germany

Location

Universitätsklinikum Standort Gießen Medizinische Klinik II u. Poliklinik Innere Med./Pneumologie

Giessen, 35392, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, 69126, Germany

Location

Fachklinik für Lungenerkrankungen

Immenhausen, 34376, 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

Semmelweis Egyetem X; Pulmonologiai Klinika

Budapest, 1083, Hungary

Location

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, 1121, Hungary

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

A.O.U. Ospedali Riuniti Di Foggia-Ospedale D'avanzo; Malattie Dell'apparato Respiratorio IV

Foggia, Apulia, 71100, Italy

Location

Ospedale Morgagni-Pierantoni; U.O. Pneumologia

Forlì, Emilia-Romagna, 47121, Italy

Location

A.O. Universitaria Policlinico Di Modena; DIP. Malattie Dell'apparato Respiratorio

Modena, Emilia-Romagna, 41124, Italy

Location

Ospedale San Giuseppe; U.O. di Pneumologia

Milan, Lombardy, 20123, Italy

Location

ASST DI MONZA; U O Clinica Pneumologica

Monza, Lombardy, 20900, Italy

Location

A.O.U. Policlinico Vittorio Emanuele; Centro per la cura delle Malattie Rare del Polmone

Catania, Sicily, 95123, Italy

Location

A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare

Siena, Tuscany, 53100, Italy

Location

Azienda Ospedaliera di Padova; Dip. Scienze Cardiologiche Toraciche Vascolari-UOC Pneumologia

Padua, Veneto, 35128, Italy

Location

Vu Medisch Centrum; Afdeling Longziekten

Amsterdam, 1081 HV, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

University of Cape Town Lung Institute; Lung Clinical Research

Cape Town, 7700, South Africa

Location

Milpark Hospital

Parktown West, 2196, South Africa

Location

University of Stellenbosch; Respiratory Research

Parow, 7505, South Africa

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 Puerta de Hierro Majadahonda; Servicio de Neumología

Majadahonda, Madrid, 28222, Spain

Location

Hospital Clinic I provincial; Servicio de Neumologia

Barcelona, 08036, Spain

Location

Hospital Universitario la Fe; Servicio de Neumologia

Valencia, 46009, Spain

Location

Ankara Uni Faculty of Medicine; Chest Diseases

Ankara, 06100, Turkey (Türkiye)

Location

Uludag University; Pulmonology and Allergy Department

Bursa, 16059, Turkey (Türkiye)

Location

Yedikule Gogus Hastaliklari ve Gogus Cerrahisi EAH;Gogus Hastaliklari

Istanbul, 34020, Turkey (Türkiye)

Location

Istanbul Universitesi Capa Tıp Fakültesi; Gogus Hastalıkları Anabilim dalı

Istanbul, 34093, Turkey (Türkiye)

Location

Ege Universitesi Tıp Fakültesi; Gögüs Hastalıkları Bilim Dalı

Izmir, 35040, Turkey (Türkiye)

Location

Related Publications (2)

• Behr J, Nathan SD, Costabel U, Albera C, Wuyts WA, Glassberg MK, Haller H Jr, Alvaro G, Gilberg F, Samara K, Lancaster L. Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies. Adv Ther. 2023 Sep;40(9):3937-3955. doi: 10.1007/s12325-023-02565-3. Epub 2023 Jun 30.

  PMID: 37391667 DERIVED

• Behr J, Nathan SD, Wuyts WA, Mogulkoc Bishop N, Bouros DE, Antoniou K, Guiot J, Kramer MR, Kirchgaessler KU, Bengus M, Gilberg F, Perjesi A, Harari S, Wells AU. Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med. 2021 Jan;9(1):85-95. doi: 10.1016/S2213-2600(20)30356-8. Epub 2020 Aug 18.

  PMID: 32822614 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Interventions

pirfenidone; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

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: October 28, 2016
• First Posted: November 1, 2016
• Study Start: December 31, 2016
• Primary Completion: September 26, 2019
• Study Completion: August 22, 2020
• Last Updated: November 12, 2020
• Results First Posted: November 12, 2020

Record last verified: 2020-10

Locations

EG (3); NL (2); TU (5); CZ (1); BE (6); DE (8); IL (7); ES (5); HU (2); IT (8); ZA (3); GR (3); CA (3)