Studying the Treatment Effect of Pirfenidone in Chronic L... | NCT03473340

NCT03473340

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Genentech, Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pirfenidone Capsule	Experimental	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily	Drug: Pirfenidone Capsule
Placebo Capsule	Placebo Comparator	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily	Drug: Placebo Capsule

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pirfenidone Capsule	Drug	Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping	Evaluate if pirfenidone compared to placebo will stabilize progression of fSAD by comparison of inspiratory and expiratory high resolution computed tomography (HRCT) images through co-registration to provide quantitative measures of fSAD.	Baseline, 24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change in Forced Expiratory Volume 1 Over 24 Weeks (FEV1)	Measured by spirometry	Baseline, 24 weeks
Change in Forced Vital Capacity (FVC) Over 24 Weeks	Measured by spirometry

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Lung transplant recipients 18 years of age or older
Greater than 6 months after single or bilateral lung transplantation
Baseline FEV1 and FVC values (mean of two highest value measured 3 weeks apart) > 50% predicted (to assure viable graft)
Diagnosis of CLAD (two consecutive spirometric values of FEV1 alone or both FEV1 and FVC < 80% of baseline)

Exclusion Criteria

Acute Rejection (AR) diagnosis by biopsy in the 28 days prior to enrollment
Treatment with pulse steroids, Anti-thymocyte Globulin (ATG), extracorporeal photopheresis (ECP), plasmapheresis, or Immunoglobulin therapy aimed at CLAD within the 28 days prior to enrollment
If the subject is receiving chronic Azithromycin therapy, the dose must be stable for the 28 days prior to enrollment
Presence of active pulmonary infection at the time of enrollment as determined by an investigator in consultation with the treating pulmonologist
Diagnosis of bronchial stenosis either a) requiring stenting, or b) thought to be responsible for the spirometric decline by principal investigator
Abnormal liver function tests (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN), Alkaline phosphatase > 2.5 x ULN, total bilirubin > ULN) or known cirrhosis (>2 times upper limit of normal of AST/ALT/AP)
Total white blood cell (WBC) < 3.0 K/uL
Moderate to Severe Renal insufficiency (CrCl <15 mL/min calculated by the Cockcroft-Gault equation)
Use of any medication known to cause significant interactions with pirfenidone (strong CYP1A2 inhibitors such as Fluvoxamine or Enoxacin or inducers)
Pregnancy or lactation. Women of child-bearing potential will have a pregnancy test at enrollment and must agree to maintain highly effective contraception with two methods of birth control from the date of consent through the end of the study.
Tobacco use within 6 months
History of alcohol abuse in the past 1 year as determined by the treating pulmonologist
Any condition other than CLAD that will likely result in death in the next 1 year
Any condition in the judgement of the principal investigator that would preclude participation in this study
EKG with QTc interval > 500 msec at screening
Listed for repeat lung transplantation

Name	Affiliation	Role
Vibha Lama, MD	University of Michigan	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
The University of Michigan		Ann Arbor	Michigan	48109	United States

Arm/Group Information

ID	Title	Description
FG000	Pirfenidone Capsule	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily Pirfenidone Capsule: Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks
FG001	Placebo Capsule	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily Placebo Capsule: Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Pirfenidone Capsule	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily Pirfenidone Capsule: Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Percent of Functional Small Airways Disease (fSAD) as Measured by Parametric Response Mapping

Evaluate if pirfenidone compared to placebo will stabilize progression of fSAD by comparison of inspiratory and expiratory high resolution computed tomography (HRCT) images through co-registration to provide quantitative measures of fSAD.

Baseline measures taken from all participants. Post treatment percentage measurements taken only from participants who completed the study.

Posted

Mean

Standard Deviation

percentage of change of fsad

Baseline, 24 weeks

ID	Title	Description
OG000	Pirfenidone Capsule	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily Pirfenidone Capsule: Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pirfenidone Capsule	Method of Administration: Oral (capsule) Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily Pirfenidone Capsule: Dosing: Days 1 through 7, 267 mg three times daily; Days 8 through 14, 534 mg three times daily; Days 15 through end of treatment (24 weeks), 801 mg three times daily duration: 24 weeks