Idiopathic Pulmonary FibrosisPhase 2NCT02951429
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
A Phase 2 study testing Pirfenidone and Sildenafil in people with Idiopathic Pulmonary Fibrosis, run by Hoffmann-La Roche at 56 sites in 13 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- Pirfenidone and Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 177 participants
- Where
- 56 sitesin 13 countries
- Study dates
- 31 Dec 2016to 22 Aug 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 6MWD 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
Who cannot join
- 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
Show all 11Show fewer
- 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
- Exclusion criteria based on pirfenidone reference safety information: 1. participants with a history of angioedema due to pirfenidone; 2. concomitant use of fluvoxamine
- Exclusion criteria based on sildenafil reference safety information: 1. co-administration with nitric oxide donors or organic nitrates, phosphodiesterase-5 (PDE5) inhibitors, guanylate cyclase stimulators, and most potent of the Cytochrome P450 3A4 (CYP3A4) inhibitors; 2. loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION); 3. use of an alpha-blocker; 4. participants with bleeding disorders or active peptic ulceration; 5. known hereditary degenerative retinal disorders such as retinitis pigmentosa; 6. galactose intolerance
Trial locations and contacts
56 sites in 13 countries.
56 sites in 13 countries
Germany8 sites
Fachkrankenhaus Coswig GmbH Zentrum f.Pneumologie Beatmungsmedizin Thorax-u.Gefäßchirurgie
Coswig, 01640
Klinik Donaustauf Zentrum für Pneumologie
Donaustauf, 93093
Ruhrlandklinik Lungenzentrum der UNI Essen Abt.Pneumologie-Allergologie
Essen, 45239
Klinikum Fulda gAG; Universitätsmedizin Marburg, Campus Fulda
Fulda, 36043
Universitätsklinikum Standort Gießen Medizinische Klinik II u. Poliklinik Innere Med./Pneumologie
Giessen, 35392
Thoraxklinik Heidelberg gGmbH
Heidelberg, 69126
Fachklinik für Lungenerkrankungen
Immenhausen, 34376
Klinikum der Universität München; Campus Großhadern; Med. Klinik und Poliklinik V
München, 81377
Italy8 sites
A.O.U. Policlinico Vittorio Emanuele; Centro per la cura delle Malattie Rare del Polmone
Catania, Sicily, 95123
A.O.U. Ospedali Riuniti Di Foggia-Ospedale D'avanzo; Malattie Dell'apparato Respiratorio IV
Foggia, Apulia, 71100
Ospedale Morgagni-Pierantoni; U.O. Pneumologia
Forlì, Emilia-Romagna, 47121
Ospedale San Giuseppe; U.O. di Pneumologia
Milan, Lombardy, 20123
A.O. Universitaria Policlinico Di Modena; DIP. Malattie Dell'apparato Respiratorio
Modena, Emilia-Romagna, 41124
ASST DI MONZA; U O Clinica Pneumologica
Monza, Lombardy, 20900
Azienda Ospedaliera di Padova; Dip. Scienze Cardiologiche Toraciche Vascolari-UOC Pneumologia
Padova, Veneto, 35128
A.O. Univ. Senese Policlinico S. Maria alle Scotte; UOC Malattie Resepiratorie e Trapianto Polmonare
Siena, Tuscany, 53100
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
Belgium6 sites
ULB Hôpital Erasme
Brussels, 1070
Cliniques Universitaires St-Luc
Brussels, 1200
UZ Antwerpen
Edegem, 2650
UZ Leuven Gasthuisberg
Leuven, 3000
CHU Sart-Tilman
Liège, 4000
CHU UCL Mont-Godinne
Mont-godinne, 5530
Spain5 sites
Hospital Clinic I provincial; Servicio de Neumologia
Barcelona, 08036
Hospital Universitari de Bellvitge ; Servicio de Neumologia
L'Hospitalet de Llobregat, Barcelona, 08097
Hospital Universitario Puerta de Hierro Majadahonda; Servicio de Neumología
Majadahonda, Madrid, 28222
Hospital Universitario Marques de Valdecilla; Servicio de neumologia
Santander, Cantabria, 39008
Hospital Universitario la Fe; Servicio de Neumologia
Valencia, 46009
Turkey (Türkiye)5 sites
Ankara Uni Faculty of Medicine; Chest Diseases
Ankara, 06100
Uludag University; Pulmonology and Allergy Department
Bursa, 16059
Yedikule Gogus Hastaliklari ve Gogus Cerrahisi EAH;Gogus Hastaliklari
Istanbul, 34020
Istanbul Universitesi Capa Tıp Fakültesi; Gogus Hastalıkları Anabilim dalı
Istanbul, 34093
Ege Universitesi Tıp Fakültesi; Gögüs Hastalıkları Bilim Dalı
Izmir, 35040
Canada3 sites
Hotel Dieu Hospital
Kingston, Ontario, K7L 2V7
CHUM Hôpital Notre-Dame
Montreal, Quebec, H2L 4M1
Institut universitaire de cardiologie et de pneumologie de Québec (Hôpital Laval)
Ste. Foy, Quebec, G1V 4G5
Egypt3 sites
Clinical Research Center (CRC), Faculty of Medicine, Alexandria University
Alexandria, 21131
Kasr El-Aini-Chest Unit; Department 3-Chest Unit
Cairo, 11562
Ain Shams University Hospital-Chest unit; Chest unit
Cairo, 11566
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
South Africa3 sites
University of Cape Town Lung Institute; Lung Clinical Research
Cape Town, 7700
Milpark Hospital
Parktown West, 2196
University of Stellenbosch; Respiratory Research
Parow, 7505
Hungary2 sites
Semmelweis Egyetem X; Pulmonologiai Klinika
Budapest, 1083
Orszagos Koranyi TBC es Pulmonologiai Intezet
Budapest, 1121
Netherlands2 sites
Vu Medisch Centrum; Afdeling Longziekten
Amsterdam, 1081 HV
Erasmus MC
Rotterdam, 3015 GD
Czechia1 site
Thomayerova nemocnice; Pneumologicka klinika 1.LF UK TN
Praha 4 - Krc, 140 59
About this study
Official title: A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Sildenafil Added to Pirfenidone in Patients With Advanced Idiopathic Pulmonary Fibrosis and Intermediate or High Probability of Group 3 Pulmonary Hypertension
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
- Being tested
- Pirfenidone, Placebo, Sildenafil
- Medical subject headings
- Idiopathic Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirfenidoneDrug
Also called Esbriet, RO0220912
Pirfenidone will be given in the range of 1602 to 2403 milligram per day (mg/day), as 3 divided doses.
PlaceboDrug
Placebo matched with sildenafil.
SildenafilDrug
Also called RO0280296
Sildenafil will be given as 20 mg, TID.
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone + Placebo | Placebo comparator | Participants will receive pirfenidone along with placebo matched to sildenafil, orally, three times a day (TID) for 52 weeks. Receives: Drug: Pirfenidone; Drug: Placebo |
| Pirfenidone + Sildenafil | Experimental | Participants will receive pirfenidone along with sildenafil, orally, TID for 52 weeks. Receives: Drug: Pirfenidone; Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to Week 52
Secondary outcomes (26)
Time to First Occurrence of Disease Progression
Disease Progression defined as relative decline in 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.
Measured: Baseline up to Week 52
Time to Multiple Occurrence of Disease Progression Events
Disease Progression defined as relative decline in 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. In case participant had more than one event as described in the endpoint definition the second, third etc event was counted as well for the calculation of the endpoint.
Measured: Baseline up to Week 52
Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15%
Measured: Baseline up to Week 52
Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD)
Measured: Baseline up to Week 52
Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52
N.A. = non-calculable
Measured: Baseline up to Week 52
Time to All-Cause Non-Elective Hospitalization
N.A. = non-calculable
Measured: Baseline up to Week 52
Time to Death From Any Cause
Measured: Baseline up to Week 52
Percentage of Participants With Lung Transplantation
Measured: Baseline up to Week 52
Time to Respiratory-Related Death
Measured: Baseline up to Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Pulmonary Artery Pressure (PAPs)
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Tricuspid Annular Plane Systolic Excursion (TAPSE)
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Right Ventricle Basal Diameter
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Inferior Vena Cava Diameter
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Left Ventricular Ejection Fraction (LVEF)
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Carbon Monoxide Diffusing Capacity/ Pulmonary Diffusing Capacity (DLCO)
Measured: Baseline, Week 52
Change From Baseline to Week 52 in Forced Vital Capacity (FVC)
Measured: Baseline, Week 52
Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52
The World Health Organisation (WHO) functional class system defines the severity of an participant's symptoms.
Class II - Participants with Pulmonary Hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue breathlessness, fatigue (tiredness), or activities that can cause chest pain, dizziness or even black outs.
Class III - Participants with Pulmonary Hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue breathlessness, fatigue (tiredness), or activities that can cause chest pain, dizziness or even black outs.
Class IV - participants with pulmonary hypertension with inability to carry out any physical activity without symptoms. These participants manifest signs of right heart failure, breathlessness and /or fatigue, which may even be present at rest. Discomfort is increased by any physical activity.
Measured: Week 52
Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Level (pg/mL) at Week 52
Measured: Baseline, Week 52
St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52
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 calculated, where the higher the component result the worse the condition:
Symptoms concerned with the effect of respiratory symptoms, their frequency and severity (range: 0-16.61) Activity concerned with activities that cause or are limited by breathlessness (range: 0-30.31) Impacts covers a range of aspects concerned with social functioning and psychological disturbances resulting from airway disease (range: 0- 53.08) 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.
Measured: Baseline, Week 52
University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Changes From Baseline at Week 52
The UCSD-SOBQ is a respiratory questionnaire and it assesses dyspnea associated with activities of daily living (ADL). Participants indicate severity of SOB on a 6-point scale in 21 ADL. Three additional questions ask about fear of harm from overexertion, limitations and fear caused by SOB. A total score ranges from 0 to 120, with higher scores indicating greater impairment.
Measured: Baseline, Week 52
Change From Baseline in Distance Walked, 6-minute Walking Distance (6MWD) Test at Week 52
Measured: Baseline up to Week 52
Change From Baseline in Oxygen Requirements, 6-minute Walking Distance (6MWD) Test at Week 52
Measured: Baseline up to Week 52
Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52
Measured: Baseline up to Week 52
Percentage of Participants With Adverse Events
Measured: Baseline up to Week 52 + 28 days
Borg Scale Result at the End of the Test at Week 52
The Borg Scale rates participant's level of perceived exertion during any activity from 0-10, with 0 being no effort at all and 10 being maximal exertion.
Measured: Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study start31 Dec 2016
- Primary completion26 Sep 2019
- Study completion22 Aug 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 (2)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies 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
- 177 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
- NCT02951429
- Sponsor's protocol ID
- MA29957
- Other IDs
- 2015-005131-40, 2015
- Status last verified
- Oct 2020
- First submitted
- 28 Oct 2016
- Last updated
- 12 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 37391667Behr 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.
PubMed 32822614
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Sildenafil Added to Pirfenidone in Patients With Advanced Idiopathic Pulmonary Fibrosis and Intermediate or High Probability of Group 3 Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT02951429
- Acronym / sponsor ID
- MA29957
- Conditions
- Idiopathic Pulmonary Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 177 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2016 (actual)
- Primary completion
- 26 Sep 2019 (actual)
- Study completion
- 22 Aug 2020 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Posted 12 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone + Placebo | Placebo comparator | Drug: Pirfenidone, Drug: PlaceboParticipants will receive pirfenidone along with placebo matched to sildenafil, orally, three times a day (TID) for 52 weeks. |
| Pirfenidone + Sildenafil | Experimental | Drug: Pirfenidone, Drug: SildenafilParticipants will receive pirfenidone along with sildenafil, orally, TID for 52 weeks. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| PirfenidoneAlso: Esbriet, RO0220912Pirfenidone will be given in the range of 1602 to 2403 milligram per day (mg/day), as 3 divided doses. | Drug | Pirfenidone + Placebo, Pirfenidone + Sildenafil |
| PlaceboPlacebo matched with sildenafil. | Drug | Pirfenidone + Placebo |
| SildenafilAlso: RO0280296Sildenafil will be given as 20 mg, TID. | Drug | Pirfenidone + Sildenafil |
Primary outcome
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
Time frame: Baseline up to Week 52
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.
26 secondary outcomes
Time to First Occurrence of Disease Progression
Time frame: Baseline up to Week 52
Time to Multiple Occurrence of Disease Progression Events
Time frame: Baseline up to Week 52
Percentage of Participants With Decline From Baseline in 6-minute Walking Distance (6MWD) of >= 15%
Time frame: Baseline up to Week 52
Time to First Occurrence of Relevant ≥15% Decline From Baseline in 6-minute Walking Distance (6MWD)
Time frame: Baseline up to Week 52
Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52
Time frame: Baseline up to Week 52
Time to All-Cause Non-Elective Hospitalization
Time frame: Baseline up to Week 52
Time to Death From Any Cause
Time frame: Baseline up to Week 52
Percentage of Participants With Lung Transplantation
Time frame: Baseline up to Week 52
Time to Respiratory-Related Death
Time frame: Baseline up to Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Pulmonary Artery Pressure (PAPs)
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Tricuspid Annular Plane Systolic Excursion (TAPSE)
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Right Ventricle Basal Diameter
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Inferior Vena Cava Diameter
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Carbon Monoxide Diffusing Capacity/ Pulmonary Diffusing Capacity (DLCO)
Time frame: Baseline, Week 52
Change From Baseline to Week 52 in Forced Vital Capacity (FVC)
Time frame: Baseline, Week 52
Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52
Time frame: Week 52
Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Level (pg/mL) at Week 52
Time frame: Baseline, Week 52
St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52
Time frame: Baseline, Week 52
University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Changes From Baseline at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Distance Walked, 6-minute Walking Distance (6MWD) Test at Week 52
Time frame: Baseline up to Week 52
Change From Baseline in Oxygen Requirements, 6-minute Walking Distance (6MWD) Test at Week 52
Time frame: Baseline up to Week 52
Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters at Week 52
Time frame: Baseline up to Week 52
Percentage of Participants With Adverse Events
Time frame: Baseline up to Week 52 + 28 days
Borg Scale Result at the End of the Test at Week 52
Time frame: Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37391667Behr 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.
- Derived from this study: PubMed 32822614Behr 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.
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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
56 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pirfenidone and Sildenafil in people with Idiopathic Pulmonary Fibrosis, run by Hoffmann-La Roche at 56 sites in 13 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 7 inclusion and 11 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 12 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in Germany, Italy, Israel, Belgium, Spain and 8 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. Some participants in this study may receive a placebo. 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 12 Nov 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?
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 (time frame: Baseline up to Week 52). 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 NCT02951429, which also lists 2 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 12 Nov 2020.