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.

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. - MA29957 / Esbriet IPF PH

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON43371

Enrollment

Registered

2016-12-12

Start date

2018-02-26

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

IPF PH

Interventions

The test products for this study are pirfenidone and sildenafil. Pirfenidone (5-methyl-1-phenyl-2-1(H)-pyridone) will be administered orally three times per day (TID) with meals, in a range of 1602 t

IDIOPATHIC PULMONARY FIBROSIS

PIRFENIDONE

PULMONARY FIBROSIS

Eligibility

Age

18 Years to 64 Years

Inclusion criteria

Inclusion criteria: - Age 40-80 years (inclusive) at Screening - 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 as defined by a measurable carbon monoxide diffusing capacity/pulmonary diffusing capacity [DLCO]

Exclusion criteria

Exclusion criteria: - History of any of the following types of PH: Group 1 pulmonary arterial hypertension (PAH); Group 2 (left-heart disease); Group 3 (due to conditions other than interstitial lung disease; Group 4 (chronic thromboembolic pulmonary hypertension); Group 5 (other disorders);- History of clinically significant cardiac disease in the opinion of the Investigator;- History of coexistent and clinically significant (in the opinion of the Investigator) COPD, bronchiectasis, asthma, inadequately treated sleep-disordered breathing, or any clinically significant pulmonary diseases or disorders other than IPF or PH secondary to IPF;- Hypotension, autonomic dysfunction, or conditions in which vasodilation may cause an unsafe drop in blood pressure (BP);- History of use of drugs and toxins known to cause PAH

Design outcomes

Primary

Measure	Time frame
The primary efficacy objective for this study is to evaluate the efficacy of adding sildenafil compared with placebo to pirfenidone treatment in patients with advanced IPF and intermediate or high probability of Group 3 PH. The primary efficacy endpoint will be evaluated based on a comparison of the proportion of patients showing disease progression over 52 weeks of treatment period, as evidenced by reaching the following combined endpoint: * Relevant decline in 6-minute walk distance (6MWD) of at least 15% from baseline (as defined below), respiratory-related non-elective hospitalization, or all-cause mortality Relevant decline in 6MWD from baseline is defined as: * Any decline >25% from baseline or * A decline between 15-25% from baseline, if accompanied by at least one of the following: o worsening of oxyhemoglobin (SpO2) desaturation during the 6-minute walk test (6MWT) compared to baseline o worsening of the maximum Borg scale during the 6MWT compared to baseline o Increased O2 requirements during the 6MWT compared to baseline	—

Measure

Time frame

The primary efficacy objective for this study is to evaluate the efficacy of adding sildenafil compared with placebo to pirfenidone treatment in patients with advanced IPF and intermediate or high probability of Group 3 PH. The primary efficacy endpoint will be evaluated based on a comparison of the proportion of patients showing disease progression over 52 weeks of treatment period, as evidenced by reaching the following combined endpoint: * Relevant decline in 6-minute walk distance (6MWD) of at least 15% from baseline (as defined below*), respiratory-related non-elective hospitalization, or all-cause mortality * Relevant decline in 6MWD from baseline is defined as: * Any decline >25% from baseline or * A decline between 15-25% from baseline, if accompanied by at least one of the following: o worsening of oxyhemoglobin (SpO2) desaturation during the 6-minute walk test (6MWT) compared to baseline o worsening of the maximum Borg scale during the 6MWT compared to baseline o Increased O2 requirements during the 6MWT compared to baseline

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Secondary

Measure	Time frame
Secondary Efficacy Objectives (Full details are given in Protocol Section 6.4.2) The secondary efficacy objective for this study is to evaluate the efficacy of adding sildenafil compared with placebo to pirfenidone treatment on the basis of the following endpoints: * Progression-free survival (PFS), defined as the time to decline in 6MWD of >=15% compared with baseline as defined above, respiratory-related non-elective hospitalization, or death from any cause * Proportion of patients with decline in 6MWD of >=15% from baseline as defined above * Time to respiratory-related non-elective hospitalization * Time to death from any cause * Lung transplantation * Time to all-cause non-elective hospitalization * Time to respiratory-related death * Change from baseline in transthoracic echocardiography (ECHO) parameters * Change from baseline in pulmonary function tests (PFTs) * Change from baseline in oxyhemoglobin saturation (SpO2) at rest and during the 6-minute walk test (6MWT) * World Health Organization (WHO) Functional Class * Dyspnea (assessed by the University of California San Diego Shortness of Breath Questionnaire - UCSD SOBQ) * Health-related quality of life (HRQoL) (assessed by the Saint Georges Respiratory Questionnaire [SGRQ]) N-terminal pro-brain natriuretic peptide (NT-proBNP) level	—

Measure

Time frame

Secondary Efficacy Objectives (Full details are given in Protocol Section 6.4.2) The secondary efficacy objective for this study is to evaluate the efficacy of adding sildenafil compared with placebo to pirfenidone treatment on the basis of the following endpoints: * Progression-free survival (PFS), defined as the time to decline in 6MWD of >=15% compared with baseline as defined above, respiratory-related non-elective hospitalization, or death from any cause * Proportion of patients with decline in 6MWD of >=15% from baseline as defined above * Time to respiratory-related non-elective hospitalization * Time to death from any cause * Lung transplantation * Time to all-cause non-elective hospitalization * Time to respiratory-related death * Change from baseline in transthoracic echocardiography (ECHO) parameters * Change from baseline in pulmonary function tests (PFTs) * Change from baseline in oxyhemoglobin saturation (SpO2) at rest and during the 6-minute walk test (6MWT) * World Health Organization (WHO) Functional Class * Dyspnea (assessed by the University of California San Diego Shortness of Breath Questionnaire - UCSD SOBQ) * Health-related quality of life (HRQoL) (assessed by the Saint George*s Respiratory Questionnaire [SGRQ]) * N-terminal pro-brain natriuretic peptide (NT-proBNP) level

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Countries

Belgium, Canada, Czechia, Egypt, Germany, Greece, Hungary, Israel, Italy, Netherlands, South Africa, Spain, Turkey, United Arab Emirates

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)