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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02951429
• Date of registration: 28/10/2016
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: 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
• Scientific 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
• Date of first enrolment: December 31, 2016
• Target sample size: 177
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02951429
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

- 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



Age minimum: 40 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: Placebo

Drug: Sildenafil

Drug: Pirfenidone

Primary Outcome(s)

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]

Secondary Outcome(s)

Change From Baseline in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Level (pg/mL) at Week 52 [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 Transthoracic Echocardiography (ECHO) Parameter: Peak Tricuspid Regurgitation Velocity [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 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: Tricuspid Annular Plane Systolic Excursion (TAPSE) [Time Frame: Baseline, Week 52]

Percentage of Participants With Adverse Events [Time Frame: Baseline up to Week 52 + 28 days]

Time to Respiratory-Related Death [Time Frame: Baseline up to Week 52]

Borg Scale Result at the End of the Test at Week 52 [Time Frame: Week 52]

Change From Baseline in Other 6-minute Walking Distance (6MWD) Parameters 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 to Week 52 in Forced Vital Capacity (FVC) [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]

Percentage of Participants With Lung Transplantation [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]

Time to First Occurrence of Relevant =15% Decline From Baseline in 6-minute Walking Distance (6MWD) [Time Frame: Baseline up to Week 52]

Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Left Ventricular Ejection Fraction (LVEF) [Time Frame: Baseline, Week 52]

St. George's Respiratory Questionnaire (SGRQ) Changes From Baseline at Week 52 [Time Frame: Baseline, Week 52]

Percentage of Participants by World Health Organization (WHO) Functional Class at Week 52 [Time Frame: Week 52]

Time to First Occurrence of Disease Progression [Time Frame: Baseline up to Week 52]

University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Changes From Baseline at Week 52 [Time Frame: Baseline, 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]

Change From Baseline to Week 52 in Transthoracic Echocardiography (ECHO) Parameter: Right Ventricle Basal Diameter [Time Frame: Baseline, Week 52]

Time to Respiratory-Related Non-Elective Hospitalization From Baseline to Week 52 [Time Frame: Baseline up to Week 52]

Secondary ID(s)

2015-005131-40

MA29957

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 12/11/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02951429