Trial Outcomes & Findings for Pirfenidone for Restrictive Chronic Lung Allograft Dysfunction (NCT NCT03359863)
NCT ID: NCT03359863
Last Updated: 2023-06-29
Results Overview
The primary outcome will be the number of subjects that discontinue pirfenidone due to a treatment emergent adverse event (TEAE)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
From initiation of pirfenidone until discontinuation or until 56 weeks, which ever comes first.
Results posted on
2023-06-29
Participant Flow
Participant milestones
| Measure |
Treatment Arm
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Overall Study
STARTED
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10
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Overall Study
COMPLETED
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5
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Overall Study
NOT COMPLETED
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5
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Age, Continuous
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55.3 years
STANDARD_DEVIATION 16.5 • n=10 Participants
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Sex: Female, Male
Female
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3 Participants
n=10 Participants
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Sex: Female, Male
Male
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7 Participants
n=10 Participants
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Body Mass Index
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28.6 kg/m^2
STANDARD_DEVIATION 7.1 • n=10 Participants
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PRIMARY outcome
Timeframe: From initiation of pirfenidone until discontinuation or until 56 weeks, which ever comes first.The primary outcome will be the number of subjects that discontinue pirfenidone due to a treatment emergent adverse event (TEAE)
Outcome measures
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Tolerability of Pirfenidone
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3 Participants
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PRIMARY outcome
Timeframe: From initiation of pirfenidone until discontinuation or until 56 weeks, which ever comes first.The outcome will be the ratio of tacrolimus-while-taking-pirfenidone to tacrolimus-before-pirfenidone corrected for the subject's specific steady-state tacrolimus concentration.
Outcome measures
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Conversion Ratio of Tacrolimus Dose
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1.1 conversion ratio
Standard Deviation 0.6
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SECONDARY outcome
Timeframe: FVC change from baseline (screening) to 1 year or death, whichever comes first.The investigators will evaluate change in FVC from baseline to 1 year after pirfenidone start based on pulmonary function tests done as part of routine clinical care (usually obtained every 3 months) or death, whichever comes first.
Outcome measures
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Annual Change in Forced Vital Capacity (FVC)
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-63.3 mL
Interval -245.5 to 118.9
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SECONDARY outcome
Timeframe: FEV1 change from baseline (screening) to 1 year or death, whichever comes first.The investigators will evaluate change in FEV1 from baseline to 1 year based on pulmonary function tests done as part of routine clinical care (usually obtained every 3 months) or death, whichever comes first.
Outcome measures
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Annual Change in Forced Expiratory Volume in 1 Second (FEV1)
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-87.8 mL
Interval -237.3 to 61.8
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SECONDARY outcome
Timeframe: Change between chest CT at screening and in 1-year follow up CT scan performed as part of routine clinical care or death, whichever comes first.The investigators will evaluate the annual change in percent of lung affected by reticulation comparing the chest CT scan at screening and a 1-year follow up CT scan performed as part of routine clinical care or death, whichever comes first.
Outcome measures
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Annual Change in Percent of Lung Affected by Reticulation on Chest CT Scan
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3 percentage of lung affected
Interval -0.8 to 6.8
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SECONDARY outcome
Timeframe: Change between Chest CT at screening and 1-year follow up CT scan performed as part of routine clinical care or death, whichever comes first.The investigators will evaluate the change in traction bronchiectasis score on chest CT scan at screening and in a 1-year follow up CT scan performed as part of routine clinical care or death, whichever comes first. The extent of traction bronchiectasis was first scored in each of the six lung lobes separately (right upper, middle, and lower lobes, and left upper, lingula, and lower lobes) as 0-absent, 1-mild, 2-moderate, or 3-severe, and then summed into a total traction bronchiectasis score \[range 0-18 points\], with higher values reflecting greater extent of traction bronchiectasis.
Outcome measures
| Measure |
Treatment Arm
n=10 Participants
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Annual Change in Traction Bronchiectasis Score on Chest CT Scan
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0.8 points
Interval -0.1 to 1.7
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Adverse Events
Treatment Arm
Serious events: 7 serious events
Other events: 10 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Treatment Arm
n=10 participants at risk
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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Respiratory, thoracic and mediastinal disorders
Hospitalization for COVID-19
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10.0%
1/10 • Up to 56 weeks for each participant
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Musculoskeletal and connective tissue disorders
Hospitalization for neck pain
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10.0%
1/10 • Up to 56 weeks for each participant
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Gastrointestinal disorders
Dizziness and Vomiting
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10.0%
1/10 • Up to 56 weeks for each participant
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Gastrointestinal disorders
Hospitalization for pseudomonas pneumonia, CMV viremia and epigastric pain
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10.0%
1/10 • Up to 56 weeks for each participant
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Skin and subcutaneous tissue disorders
Hospitalization for cellulitis of the neck
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20.0%
2/10 • Up to 56 weeks for each participant
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Respiratory, thoracic and mediastinal disorders
Hospitalization for progressive respiratory failure leading to retransplant
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20.0%
2/10 • Up to 56 weeks for each participant
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Eye disorders
Hospitalization for herpes zoster ophtalmicus
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10.0%
1/10 • Up to 56 weeks for each participant
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Respiratory, thoracic and mediastinal disorders
Hospitalization for pneumonia with Aspergillus
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10.0%
1/10 • Up to 56 weeks for each participant
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Other adverse events
| Measure |
Treatment Arm
n=10 participants at risk
Subjects will receive Pirfenidone as part of treatment for their restrictive chronic lung allograft dysfunction (RCLAD).
Pirfenidone: Subjects will receive pirfenidone for 52 weeks, titrated to 2403 mg/day (3 capsules, 3× daily) after a 4-week titration period (1 capsule, 3x daily for 2 weeks, 2 capsules, 3x daily for 2 weeks) for a total of 56 weeks of pirfenidone. Eligible participants will continue pirfenidone beyond 56 weeks.
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|---|---|
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Gastrointestinal disorders
Nausea
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70.0%
7/10 • Up to 56 weeks for each participant
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Gastrointestinal disorders
Vomiting
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50.0%
5/10 • Up to 56 weeks for each participant
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Musculoskeletal and connective tissue disorders
Myalgia
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70.0%
7/10 • Up to 56 weeks for each participant
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Gastrointestinal disorders
Diarrhea
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60.0%
6/10 • Up to 56 weeks for each participant
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Gastrointestinal disorders
Constipation
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50.0%
5/10 • Up to 56 weeks for each participant
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General disorders
Fatigue
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90.0%
9/10 • Up to 56 weeks for each participant
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General disorders
Dizziness/Lightheadedness
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60.0%
6/10 • Up to 56 weeks for each participant
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Nervous system disorders
Neuropathy - sensory
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40.0%
4/10 • Up to 56 weeks for each participant
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General disorders
Headache
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80.0%
8/10 • Up to 56 weeks for each participant
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Musculoskeletal and connective tissue disorders
Muscle weakness
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50.0%
5/10 • Up to 56 weeks for each participant
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Ear and labyrinth disorders
Inner ear / hearing
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40.0%
4/10 • Up to 56 weeks for each participant
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Skin and subcutaneous tissue disorders
Photosensitivity / Phototoxicity
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20.0%
2/10 • Up to 56 weeks for each participant
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Nervous system disorders
Neuropathy - motor
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20.0%
2/10 • Up to 56 weeks for each participant
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Musculoskeletal and connective tissue disorders
Arthralgia
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70.0%
7/10 • Up to 56 weeks for each participant
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General disorders
Alopecia
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50.0%
5/10 • Up to 56 weeks for each participant
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Cardiac disorders
Hypertension
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90.0%
9/10 • Up to 56 weeks for each participant
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Psychiatric disorders
Mood alteration
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60.0%
6/10 • Up to 56 weeks for each participant
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Eye disorders
Ocular / visual
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50.0%
5/10 • Up to 56 weeks for each participant
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Metabolism and nutrition disorders
Anorexia
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30.0%
3/10 • Up to 56 weeks for each participant
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|
Infections and infestations
Wound - infections
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20.0%
2/10 • Up to 56 weeks for each participant
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|
Metabolism and nutrition disorders
Dehydration
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20.0%
2/10 • Up to 56 weeks for each participant
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Nervous system disorders
Confusion
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20.0%
2/10 • Up to 56 weeks for each participant
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Infections and infestations
Fever
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10.0%
1/10 • Up to 56 weeks for each participant
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Skin and subcutaneous tissue disorders
Rash / desquamation
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10.0%
1/10 • Up to 56 weeks for each participant
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Nervous system disorders
Neuropathy - cerebellar
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10.0%
1/10 • Up to 56 weeks for each participant
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|
Nervous system disorders
Ataxia
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10.0%
1/10 • Up to 56 weeks for each participant
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Additional Information
Aida Venado, MD, MAS
University of California at San Francisco
Phone: 4153532577
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place