Open-label Study to Assess the Effectiveness of Pirfenidone in Participants With Idiopathic Pulmonary Fibrosis (IPF).

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03208933
• Collaborator: (none)
• Enrollment: 60
• Locations: 11
• Arm: 1
• Actual Duration (Months): 24.7
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is a national, multicenter, interventional, non-randomized, non-controlled, open-label study to assess the effectiveness of pirfenidone in participants with IPF in Russian clinical practice.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Pirfenidone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Local Open-label Multicenter Study to Assess the Effectiveness of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis in Russian Clinical Practice
• Actual Study Start Date: Oct 23, 2017
• Actual Primary Completion Date: Nov 13, 2019
• Actual Study Completion Date: Nov 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pirfenidone Participants will be administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks in participants with IPF.	Drug: Pirfenidone; Pirfenidone 2403 mg/d capsules orally will be given in divided doses (TID) after titration period of 14 days.; Other Names: Esbriet, RO0220912

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 26 in Absolute Millilitre (mL) Forced Vital Capacity (FVC) [Baseline, Week 26]

   FVC is a standard pulmonary function test. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Baseline FVC will be the average of the highest FVC measurement recorded at the Screening and Day 1. The FVC at Week 26 will be the average of the highest FVC measurement recorded on two separate days at Week 26.

2. Change From Baseline to Week 26 in Percent (%) Predicted FVC [Baseline, Week 26]

   Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100.

Secondary Outcome Measures

1. Change From Baseline to Week 26 in 6-Minute Walk Test (6MWT) Distance [Baseline, Week 26]

   Baseline 6MWT distance will be the average of the measurements recorded at the Screening and Day 1 visits. The 6MWT distance at Week 26 will be defined as the average of the 6MWT distance recorded on two separate days at Week 26.

2. Change From Baseline to Week 26 in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score [Baseline, Week 26]

   The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.

3. Change From Baseline to Week 26 in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score [Baseline, Week 26]

   The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

4. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [Up to Week 52]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Serious adverse event is any untoward medical occurrence at any dose that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, or resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical symptoms consistent with IPF of ≥ 6months duration

• Participants could have both "confident" or "consistent" with UIP diagnosis of IPF based on clinical, radiologic and pathologic data according to 2011 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines at the Screening. HRCT scan performed within 24 months before the start of the Screening may be used, if it meets all image acquisition guideline

• No features supporting an alternative diagnosis on transbronchial biopsy, bronchoalveolar lavage (BAL), or surgical lung biopsy, if performed. Results of the surgical lung biopsy performed within the last 4 years must be confirmed by central review

• Participants with %FVC ≥ 40 % at the Screening

• Participants with %Carbon monoxide diffusing capacity (DLCO) ≥ 30 % at the Screening

• Ability to walk ≥ 100 m during the 6-minute walk test at the Screening

• Eligible participants must discontinue all prohibited medications at least 28 days before the Screening

• Female participants of childbearing potential must have negative urine pregnancy test at the Screening and before first dosing on Day 1

Exclusion Criteria:

• Significant clinical worsening of IPF between Screening and Day 1, in the opinion of the investigator

• Relevant airways obstruction (i.e. pre-bronchodilator forced expiratory volume (FEV)1/FVC < 0.7)

• Cigarette smoking within 28 days before the start of treatment or unwilling to avoid tobacco products throughout the study

• History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds

• Known explanation for interstitial lung disease, including but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer

• Clinical diagnosis of any connective tissue disease, including but not limited to scleroderma, polymyositis/ dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis

• During baseline analysis of HRCT, significant coexistent emphysema (emphysema extent greater than extent of fibrosis) confirmed by central review

• Planned lung transplantation during the study

• Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis

• Unable to perform 6MWT or to undergo pulmonary function test

• Any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 1 years. This does not include minor surgical procedures for localized cancer (e.g., basal cell carcinoma)

• History of severe hepatic impairment or end-stage liver disease

• History of end-stage renal disease requiring dialysis

• History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months

• Pregnancy or lactation, or intention to become pregnant during the study. Women of childbearing capacity are required to have a negative urine pregnancy test before treatment and must agree to maintain highly effective contraception

• Liver function test outside specified limits at the Screening: total bilirubin above the upper limit of normal (ULN); aspartate or alanine aminotransferase (AST or ALT) > 3 × ULN; alkaline phosphatase > 2.5 × ULN

• Creatinine clearance < 30 mL/min, calculated using the Cockcroft-Gault formula

• Electrocardiogram (ECG) with a QT interval corrected according to Fridericia's formula (QTcF) > 500 msec at the Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regional State Budgetary Institution of Healthcare "Regional Cinilcal Hospital"; Pulmonology	Barnaul	Altaj	Russian Federation	656024
2	GBUZ Regional clinical hospital #4	Chelyabinsk	Evenkija	Russian Federation
3	SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF	Sankt-peterburg	Leningrad	Russian Federation	197022
4	Central NII tuberkuleza RAMN	Moscow	Moskovskaja Oblast	Russian Federation
5	Pulmonologii NII FMBA of Russia	Moscow	Moskovskaja Oblast	Russian Federation
6	New Hospital	Yekaterinburg	Sverdlovsk	Russian Federation
7	I.M. Sechenov First Moscow State Medical University: The E.M. Tareyev Clinic	Moscow		Russian Federation	119992
8	Vladimirskiy Regional Scientific Research Inst.	Moscow		Russian Federation	129110
9	State Novosibirsk Regional Clinical Hospital	Novosibirsk		Russian Federation	630087
10	Republican clinical hospital named after G.G. Kuvatov	UFA		Russian Federation	450005
11	Budget Institution of Healthcare of Voronezh Region "Voronezh Regional Clinical Hospital #1"	Voronezh		Russian Federation	394066

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Feb 1, 2019
• Statistical Analysis Plan - Jun 17, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03208933
• Other Study ID Numbers: ML39355
• First Posted: Jul 6, 2017
• Last Update Posted: Nov 20, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Hoffmann-La Roche: Pirfenidone, UIP, IPF, FVC
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pirfenidone

Study Results

Participant Flow

Recruitment Details	The study enrolled participants in Russia.

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Period Title: Overall Study
STARTED	60
COMPLETED	47
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Overall Participants	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.4 (7.75)
Sex: Female, Male (Count of Participants)
Female	19 31.7%
Male	41 68.3%
Race/Ethnicity, Customized (Count of Participants)
Russian	48 80%
Tatar	4 6.7%
Bashkir	4 6.7%
Armenian	1 1.7%
Dagestani	1 1.7%
Kazah	1 1.7%
Uzbek	1 1.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 26 in Absolute Millilitre (mL) Forced Vital Capacity (FVC)
Description	FVC is a standard pulmonary function test. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Baseline FVC will be the average of the highest FVC measurement recorded at the Screening and Day 1. The FVC at Week 26 will be the average of the highest FVC measurement recorded on two separate days at Week 26.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Included participants that had data for at least one post-baseline assessment of any efficacy measurement

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Measure Participants	55
Mean (95% Confidence Interval) [Milliliter (mL)]	128.78

2. Primary Outcome

Title	Change From Baseline to Week 26 in Percent (%) Predicted FVC
Description	Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = [(observed FVC)/(predicted FVC)]*100.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Included participants that had data for at least one post-baseline assessment of any efficacy measurement

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Measure Participants	55
Mean (95% Confidence Interval) [percent predicted]	-0.10

3. Secondary Outcome

Title	Change From Baseline to Week 26 in 6-Minute Walk Test (6MWT) Distance
Description	Baseline 6MWT distance will be the average of the measurements recorded at the Screening and Day 1 visits. The 6MWT distance at Week 26 will be defined as the average of the 6MWT distance recorded on two separate days at Week 26.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Included participants that had data for at least one post-baseline assessment of any efficacy measurement and for the 6MWT at Week 26

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Measure Participants	49
Decline of >= 50 m	14 23.3%
Decline of <50 m to 0 m	11 18.3%
Improvement of >= 0 m	24 40%

4. Secondary Outcome

Title	Change From Baseline to Week 26 in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score
Description	The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Included participants that had data for at least one post-baseline assessment of any efficacy measurement

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Measure Participants	55
Mean (Standard Deviation) [score on scale]	-0.0288 (0.1820)

5. Secondary Outcome

Title	Change From Baseline to Week 26 in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score
Description	The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Included participants that had data for at least one post-baseline assessment of any efficacy measurement

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Measure Participants	55
Mean (Standard Deviation) [score on scale]	-0.6 (17.16)

6. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. Serious adverse event is any untoward medical occurrence at any dose that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of hospitalization, or resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
Measure Participants	60
TEAEs	81.7 136.2%
TESAEs	16.7 27.8%

Adverse Events

Time Frame	Up to 52 Weeks
Arm/Group Title	Pirfenidone
Arm/Group Description	Participants administered pirfenidone 2403 milligram per day (mg/d) orally for 26 weeks
All Cause Mortality
	Pirfenidone
	Affected / at Risk (%)	# Events
Total	7/60 (11.7%)
Serious Adverse Events
	Pirfenidone
	Affected / at Risk (%)	# Events
Total	10/60 (16.7%)
Cardiac disorders
Atrial fibrillation	1/60 (1.7%)	1
Atrial flutter	1/60 (1.7%)	1
General disorders
Death	2/60 (3.3%)	2
Sudden cardiac death	1/60 (1.7%)	1
Infections and infestations
Bronchitis bacterial	1/60 (1.7%)	1
Cholecystitis infective	1/60 (1.7%)	1
Pneumonia	1/60 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis	2/60 (3.3%)	3
Bronchitis chronic	1/60 (1.7%)	1
Dyspnoea	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Pirfenidone
	Affected / at Risk (%)	# Events
Total	32/60 (53.3%)
Gastrointestinal disorders
Nausea	16/60 (26.7%)
Dyspepsia	8/60 (13.3%)
Vomiting	8/60 (13.3%)
Diarrhoea	7/60 (11.7%)
Investigations
Weight decreased	4/60 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	13/60 (21.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	6/60 (10%)
Cough	4/60 (6.7%)
Skin and subcutaneous tissue disorders
Pruritus	4/60 (6.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights