Trial Outcomes & Findings for Scleroderma Lung Study III - Combining Pirfenidone With Mycophenolate (NCT NCT03221257)
NCT ID: NCT03221257
Last Updated: 2023-12-15
Results Overview
Change from baseline to month 18 in the mean forced vital capacity (represented as the percentage of the age-; height-; gender-; and race-adjusted predicted value, i.e. FVC-%).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
51 participants
Primary outcome timeframe
Baseline to 18 months
Results posted on
2023-12-15
Participant Flow
88 consented with 31 subsequently deemed ineligible, 6 withdrawals prior to randomization, resulting in 51 participants considered enrolled, eligible and randomized.
Participant milestones
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
27
|
|
Overall Study
COMPLETED
|
23
|
25
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
The disease duration was not available for all participants.
Baseline characteristics by cohort
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52.6 years
STANDARD_DEVIATION 10 • n=24 Participants
|
56.6 years
STANDARD_DEVIATION 9.9 • n=27 Participants
|
54.7 years
STANDARD_DEVIATION 10.1 • n=51 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=24 Participants
|
19 Participants
n=27 Participants
|
36 Participants
n=51 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=24 Participants
|
8 Participants
n=27 Participants
|
15 Participants
n=51 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=24 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=24 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=24 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=24 Participants
|
3 Participants
n=27 Participants
|
5 Participants
n=51 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=24 Participants
|
22 Participants
n=27 Participants
|
41 Participants
n=51 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=24 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=51 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=24 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=51 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=24 Participants
|
27 participants
n=27 Participants
|
51 participants
n=51 Participants
|
|
Scleroderma Classification
Sine
|
3 Participants
n=24 Participants
|
3 Participants
n=27 Participants
|
6 Participants
n=51 Participants
|
|
Scleroderma Classification
Limited
|
13 Participants
n=24 Participants
|
11 Participants
n=27 Participants
|
24 Participants
n=51 Participants
|
|
Scleroderma Classification
Diffuse
|
8 Participants
n=24 Participants
|
13 Participants
n=27 Participants
|
21 Participants
n=51 Participants
|
|
Disease Duration
|
32.9 months
STANDARD_DEVIATION 24.2 • n=23 Participants • The disease duration was not available for all participants.
|
28.9 months
STANDARD_DEVIATION 25.4 • n=26 Participants • The disease duration was not available for all participants.
|
30.8 months
STANDARD_DEVIATION 24.7 • n=49 Participants • The disease duration was not available for all participants.
|
|
Percent predicted forced vital capacity (FVC-%)
|
71.5 percent predicted
STANDARD_DEVIATION 9.9 • n=24 Participants
|
70.6 percent predicted
STANDARD_DEVIATION 11.0 • n=27 Participants
|
71.0 percent predicted
STANDARD_DEVIATION 10.4 • n=51 Participants
|
|
Forced Vital Capacity volume (FVC)
|
2705 ml
STANDARD_DEVIATION 540 • n=24 Participants
|
2610 ml
STANDARD_DEVIATION 781 • n=27 Participants
|
2655 ml
STANDARD_DEVIATION 674 • n=51 Participants
|
|
Percent predicted single-breath diffusing capacity for carbon monoxide (DLCOHb-%)
|
55.6 percent predicted
STANDARD_DEVIATION 14.4 • n=24 Participants • DLCOHb-% was not available for all participants.
|
54.6 percent predicted
STANDARD_DEVIATION 12.0 • n=26 Participants • DLCOHb-% was not available for all participants.
|
55.1 percent predicted
STANDARD_DEVIATION 13.0 • n=50 Participants • DLCOHb-% was not available for all participants.
|
|
Mahler Baseline Dyspnea Index
|
6.8 units on a scale
STANDARD_DEVIATION 1.5 • n=24 Participants
|
6.9 units on a scale
STANDARD_DEVIATION 2.0 • n=27 Participants
|
6.9 units on a scale
STANDARD_DEVIATION 1.8 • n=51 Participants
|
|
Modified Rodnan Skin Score (mRSS)
|
8.1 units on a scale
STANDARD_DEVIATION 7.6 • n=24 Participants
|
11.7 units on a scale
STANDARD_DEVIATION 9.9 • n=27 Participants
|
10.0 units on a scale
STANDARD_DEVIATION 9.0 • n=51 Participants
|
|
Health Assessment Questionnaire Disability Index (HAQ-DI)
|
0.4 units on a scale
STANDARD_DEVIATION 0.4 • n=24 Participants
|
0.5 units on a scale
STANDARD_DEVIATION 0.6 • n=27 Participants
|
0.5 units on a scale
STANDARD_DEVIATION 0.5 • n=51 Participants
|
|
Quantitative lung fibrosis score in the whole lung (QLF-WL)
|
6.0 percent
STANDARD_DEVIATION 5.1 • n=23 Participants • HRCT data was not available for all participants.
|
6.5 percent
STANDARD_DEVIATION 6.0 • n=26 Participants • HRCT data was not available for all participants.
|
6.3 percent
STANDARD_DEVIATION 5.5 • n=49 Participants • HRCT data was not available for all participants.
|
|
Quantitative lung fibrosis score in the lobe of maximal involvement (QLF-LM)
|
14.5 percent
STANDARD_DEVIATION 14.0 • n=23 Participants • HRCT data was not available for all participants.
|
16.3 percent
STANDARD_DEVIATION 17.4 • n=26 Participants • HRCT data was not available for all participants.
|
15.4 percent
STANDARD_DEVIATION 15.7 • n=49 Participants • HRCT data was not available for all participants.
|
|
Quantitative interstitial lung disease score in the whole lung (QILD-WL)
|
24.1 percent
STANDARD_DEVIATION 11.3 • n=23 Participants • HRCT data was not available for all participants.
|
23.8 percent
STANDARD_DEVIATION 11.8 • n=26 Participants • HRCT data was not available for all participants.
|
23.9 percent
STANDARD_DEVIATION 11.4 • n=49 Participants • HRCT data was not available for all participants.
|
|
Quantitative interstitial lung disease score in the lobe of maximal involvement (QILD-LM)
|
42.0 percent
STANDARD_DEVIATION 17.9 • n=23 Participants • HRCT data was not available for all participants.
|
41.8 percent
STANDARD_DEVIATION 19.5 • n=26 Participants • HRCT data was not available for all participants.
|
41.9 percent
STANDARD_DEVIATION 18.6 • n=49 Participants • HRCT data was not available for all participants.
|
|
Total lung capacity (TLC)
|
3859 ml
STANDARD_DEVIATION 883 • n=23 Participants • HRCT data was not available for all participants.
|
3717 ml
STANDARD_DEVIATION 874 • n=26 Participants • HRCT data was not available for all participants.
|
3783 ml
STANDARD_DEVIATION 872 • n=49 Participants • HRCT data was not available for all participants.
|
PRIMARY outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from baseline to month 18 in the mean forced vital capacity (represented as the percentage of the age-; height-; gender-; and race-adjusted predicted value, i.e. FVC-%).
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percent Predicted Forced Vital Capacity (FVC-%)
|
2.24 percent predicted
Standard Error 1.351
|
2.09 percent predicted
Standard Error 1.278
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from baseline to month 18 in DLCO, calculated as a percent of the age-; height-; gender-; race-; and hemoglobin-adjusted predicted value (DLCOHb-%). The raw DLCO value and adjusting it for all of these factors and presenting it as a percent of predicted (expected) is the outcome measure (DLCOHb-%).
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=25 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percent Predicted Single-breath Diffusing Capacity for Carbon Monoxide (DLCOHb-%)
|
1.25 percent predicted
Standard Error 1.549
|
1.24 percent predicted
Standard Error 1.505
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from baseline to month 18 in the mRSS. mRSS scores have a range from 0 to 51, with higher score indicating greater skin involvement.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Modified Rodnan Skin Score (mRSS)
|
-5.42 score on a scale
Standard Error 1.164
|
-4.96 score on a scale
Standard Error 1.109
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from baseline to month 18 in the Forced Vital Capacity volume (FVC, in ml)
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Forced Vital Capacity Volume (FVC, in ml)
|
121.53 ml
Standard Error 62.41
|
112.33 ml
Standard Error 59.055
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
The change from baseline to 18 months in dyspnea. The TDI score for each of three domains ranges from -3 (major deterioration) to +3 (major improvement). The sum of all domains yields the TDI total score (-9 to +9).
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Mahler Modified Transitional Dyspnea Index (TDI)
|
1.13 score on a scale
Standard Error 0.754
|
1.99 score on a scale
Standard Error 0.710
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from baseline to month 18 as a subjective measure of dyspnea and quality of life. HAQ-DI ranges from 0 (no disability) to 3 (severe disability).
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=26 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Health Assessment Questionnaire Modified for Scleroderma (HAQ-DI)
|
-0.03 score on a scale
Standard Error 0.109
|
-0.17 score on a scale
Standard Error 0.103
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from baseline to month 18 as a subjective measure of dyspnea and quality of life. SGRQ ranges from 0 (no impairment) to 100 (maximum impairment).
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
St. George's Respiratory Questionnaire (SGRQ)
|
-4.77 score on a scale
Standard Error 3.487
|
-6.11 score on a scale
Standard Error 3.212
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from screening to month 18 in computer-generated scoring of HRCT data from the whole lung for the percentage of imaging pixels that exhibit features characteristic for lung fibrosis. Individual image scores range 0 to 100%, with higher percentages representing greater extent of quantitative lung fibrosis.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Whole Lung (QLF-WL)
|
1.46 percent
Standard Error 0.994
|
-0.11 percent
Standard Error 0.935
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from screening to month 18 in computer-generated scoring of HRCT data for the percentage of imaging pixels that exhibit features characteristic for lung fibrosis within the lobe of maximal involvement at baseline. Individual image score range 0 to 100%, with higher percentages representing greater extent of quantitative lung fibrosis.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Lobe of Maximal Involvement (QLF-LM)
|
2.57 percent
Standard Error 2.276
|
0.13 percent
Standard Error 2.132
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from screening to month 18 in computer-generated scoring of HRCT data from the whole lung for the percentage of imaging pixels that exhibit features of any of the three patterns of interstitial lung disease (ILD) including quantitative ground-glass opacity (QGG), lung fibrosis (QLF) and quantitative honeycombing (QHC). Individual image scores range 0 to 100%, with higher percentages representing greater extent of quantitative interstitial lung disease.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL)
|
2.36 percent
Standard Error 1.919
|
-1.15 percent
Standard Error 1.829
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from screening to month 18 in computer-generated scoring of HRCT data for the percentage of imaging pixels exhibiting features characteristic for any of three patterns of ILD (including QGG, QLF and QHC) within the lobe of maximal involvement at baseline. Individual image scores range 0 to 100%, with higher percentages representing greater extent of quantitative interstitial lung disease.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Lobe of Maximal Involvement (QILD-LM)
|
2.99 percent
Standard Error 2.634
|
-0.99 percent
Standard Error 2.486
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Screening to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
Change from screening to 18 months in quantitative HRCT measurement of TLC at maximal inspiration (HRCT-TLC). Higher scores indicates a better outcome.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
High Resolution Computerized Tomography (HRCT) Measures of Total Lung Capacity (TLC)
|
70.69 ml
Standard Error 78.986
|
191.99 ml
Standard Error 73.738
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
The time (in months) required for each treatment arm to achieve a 3.0% or greater improvement from baseline in the FVC-% over the 18-month treatment period.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
3.0% or Greater Improvement From Baseline in FVC-%.
|
17.8 months
Interval 8.9 to
Due to the fact that the number of events is insufficient to calculate the upper confidence limit.
|
12.3 months
Interval 3.6 to 18.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: The modified intention-to-treat population (m-ITT) is defined as all participants randomized, receiving at least one dose of study medication, and having at least one post-baseline efficacy assessment.
The percentage of subjects in each treatment arm achieving greater than a 5% improvement in FVC-% over the 18-month treatment period.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=22 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Greater Than 5% Improvement in FVC-%
|
6 Participants
|
9 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Completers population for FVC-% includes all subjects in the modified intent-to-treat population who had an 18-month FVC-% (regardless of completion of study medication).
The percentage of participants in each treatment arm achieving either improvements in the absolute change of FVC-% from baseline to 18 months by up to 5%, from 5% to \<10% and from 10% to \<15% or worsening by up to 5%, from 5% to \<10% and from 10% to \<15%. The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=22 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-%
≥ 10% to < 15%
|
1 Participants
|
1 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-%
≥ 5% to < 10%
|
5 Participants
|
8 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-%
> 0% to < 5%
|
10 Participants
|
6 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-%
> -5% to ≤ 0%
|
5 Participants
|
6 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-%
> -10% to ≤ -5%
|
1 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Completers population for FVC-% includes all subjects in the modified intent-to-treat population who had an 18-month FVC-% (regardless of completion of study medication).
The percentage of participants in each treatment arm who are defined as positive responders (improved at least 3% or more) or negative responders (worsened at least 3% or more), and stable (\>-3% to \<3%). The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=22 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders
Positive responder (≥ 3%)
|
8 Participants
|
11 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders
Stable (> -3 to < 3)
|
10 Participants
|
8 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders
Negative responder (≤ -3%)
|
4 Participants
|
4 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Completers population for FVC-% includes all subjects in the modified intent-to-treat population who had an 18-month FVC-% (regardless of completion of study medication).
The percentage of participants in each treatment arm who are defined as any responders (improved \>0%) or any non-responders (worsened \</=0%). The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=22 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders
Responder (> 0%)
|
16 Participants
|
15 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders
Non-responder (≤ 0%)
|
6 Participants
|
8 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Completers population for mRSS includes all subjects in the modified intent-to-treat population who had an 18-month mRSS (regardless of completion of study medication).
The percentage of participants in each treatment arm achieving changes in 4 point increments: worsen (1 to 4, \>/=5), no change (=0), improved (\</=-13, -12 to -9, -8 to -5, -4 to -1). The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
≤ -13
|
2 Participants
|
6 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
-12 to -9
|
1 Participants
|
0 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
-8 to -5
|
4 Participants
|
4 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
-4 to -1
|
8 Participants
|
9 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
0
|
3 Participants
|
3 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
1 to 4
|
1 Participants
|
1 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS
≥ 5
|
1 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Completers population for mRSS includes all subjects in the modified intent-to-treat population who had an 18-month mRSS (regardless of completion of study medication).
The percentage of participants in each treatment arm achieving changes defined as improved (\</=-5), no change (-5 to 5), and decreased (\>5). The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=20 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased.
Worsening (change > 5)
|
0 Participants
|
0 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased.
No Change (-5 ≤ change ≤ 5)
|
15 Participants
|
13 Participants
|
|
Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased.
Improvement (change < -5)
|
5 Participants
|
10 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Completers population for TDI includes all subjects in the modified intent-to-treat population who had an 18-month TDI (regardless of completion of study medication).
The percentage of participants in each treatment arm achieving either improvements in the TDI focal score at 18 months by 1-3, 4-6 and 7-9 points, no change (0) and worsened by 1-3, 4-6and 7-9 points. The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=25 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
-6 to -4
|
3 Participants
|
5 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
-9 to -7
|
1 Participants
|
4 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
-3 to -1
|
6 Participants
|
2 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
7 to 9
|
0 Participants
|
0 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
4 to 6
|
1 Participants
|
1 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
1 to 3
|
4 Participants
|
5 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
0
|
8 Participants
|
8 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 18 monthsPopulation: Completers population for TDI includes all subjects in the modified intent-to-treat population who had an 18-month TDI (regardless of completion of study medication).
The percentage of participants in each treatment arm achieving TDI focal scores defined as improved (\>0), no change and deterioration (\<0). The descriptive analysis is presented.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=23 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=25 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration
Worsening (change < 0)
|
5 Participants
|
6 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration
No Change (change = 0)
|
8 Participants
|
8 Participants
|
|
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration
Improvement (change > 0)
|
10 Participants
|
11 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Safety population includes all the randomized participants who received at least one dose of study medication.
The time from start of treatment to withdrawal or removal from active drug therapy (MMF or Plac/PFD separately) for any reason will be plotted over the course of the 18-month treatment as a measure of tolerability and toxicity. Median times to withdrawal are not available for reporting as less than half of the participants discontinued the study drugs.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Time to Withdrawal From the Study Drug or Treatment Failure
|
NA days
Insufficient number of events to calculate the median, lower, or upper confidence limit.
|
NA days
Insufficient number of events to calculate the median, lower, or upper confidence limit.
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to 18 monthsPopulation: Safety population includes all the randomized participants who received at least one dose of study medication.
Adverse Events (AE) and Serious Adverse Events (SAE), classified according to preferred MedDRA terms, were systematically recorded over the course of the 18-month treatment period as a measure of toxicity. Total number of participants experiencing adverse events reported here. Complete breakdown of AE and SAE by MedDRA terms is reported in the Adverse Events section.
Outcome measures
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 Participants
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 Participants
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Number of Participants With Treatment-related Adverse Events as Assessed by System Organ Classification Using Preferred Medical Dictionary for Regulatory Activities (MedDRA) Terms.
|
23 Participants
|
27 Participants
|
Adverse Events
Placebo (Plac) + Mycophenolate (MMF)
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Pirfenidone (PFD) + Mycophenolate (MMF)
Serious events: 4 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 participants at risk
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 participants at risk
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Cardiac disorders
Right Sided Chest Pain
|
0.00%
0/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Colitis
|
4.2%
1/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Infections and infestations
Covid-19 Infection
|
4.2%
1/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Infections and infestations
Herpes Zoster Ophthalmicus
|
0.00%
0/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma, Nodular
|
0.00%
0/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Extra-nodal Marginal Zone B-cell Lymphoma of the Stomach and Antrum
|
0.00%
0/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Renal and urinary disorders
Scleroderma Renal Crisis
|
0.00%
0/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute Chronic Hypoxemic Respiratory Failure
|
4.2%
1/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
Other adverse events
| Measure |
Placebo (Plac) + Mycophenolate (MMF)
n=24 participants at risk
Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Placebo (Plac): Participants will receive a Plac, matched to resemble PFD, titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
Pirfenidone (PFD) + Mycophenolate (MMF)
n=27 participants at risk
Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).
Pirfenidone (PFD): Participants will receive PFD titrated up to a target dose of 801 mg taken three times daily as tolerated (3-step titration occurring at 2 week intervals).
Mycophenolate Mofetil (MMF): Participants will receive MMF titrated up to a target dose of 1500 mg taken twice daily as tolerated (4-step titration occurring at monthly intervals).
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
8.3%
2/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.3%
2/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Cardiac disorders
Chest Pain (Cardiac)
|
8.3%
2/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Eye disorders
Dry Eyes
|
16.7%
4/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
20.8%
5/24 • 1 year and 6 months
|
14.8%
4/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Bloating
|
4.2%
1/24 • 1 year and 6 months
|
11.1%
3/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Blood in Stool
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Constipation
|
8.3%
2/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
41.7%
10/24 • 1 year and 6 months
|
44.4%
12/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Dysphagia
|
8.3%
2/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Gastro-esophageal Reflux Disease (GERD)
|
8.3%
2/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Heartburn
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Loose Stools
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Loss of Appetite
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Nausea
|
29.2%
7/24 • 1 year and 6 months
|
81.5%
22/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Stomach Pain
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Upset Stomach
|
8.3%
2/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Vomiting (Emesis)
|
16.7%
4/24 • 1 year and 6 months
|
40.7%
11/27 • 1 year and 6 months
|
|
Gastrointestinal disorders
Worsening GERD
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
General disorders
Dizziness
|
4.2%
1/24 • 1 year and 6 months
|
18.5%
5/27 • 1 year and 6 months
|
|
General disorders
Fatigue
|
20.8%
5/24 • 1 year and 6 months
|
29.6%
8/27 • 1 year and 6 months
|
|
General disorders
Fever
|
12.5%
3/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
General disorders
Headache
|
20.8%
5/24 • 1 year and 6 months
|
22.2%
6/27 • 1 year and 6 months
|
|
General disorders
Insomnia
|
4.2%
1/24 • 1 year and 6 months
|
14.8%
4/27 • 1 year and 6 months
|
|
Hepatobiliary disorders
ALT Increased
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Infections and infestations
COVID-19
|
0.00%
0/24 • 1 year and 6 months
|
14.8%
4/27 • 1 year and 6 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Infections and infestations
Upper Respiratory Tract Infection (URI)
|
8.3%
2/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Infections and infestations
Urinary Tract Infection (UTI)
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Infections and infestations
Yeast Infection
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Metabolism and nutrition disorders
Weight Loss
|
0.00%
0/24 • 1 year and 6 months
|
11.1%
3/27 • 1 year and 6 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
8.3%
2/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Musculoskeletal and connective tissue disorders
Joint Pain
|
12.5%
3/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Nervous system disorders
Headache
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Nervous system disorders
Tremors
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Psychiatric disorders
Anxiety
|
8.3%
2/24 • 1 year and 6 months
|
11.1%
3/27 • 1 year and 6 months
|
|
Psychiatric disorders
Depression
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Renal and urinary disorders
Urinary Tract Infection (UTI)
|
4.2%
1/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
20.8%
5/24 • 1 year and 6 months
|
0.00%
0/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cold
|
8.3%
2/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.8%
5/24 • 1 year and 6 months
|
25.9%
7/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
2/24 • 1 year and 6 months
|
3.7%
1/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Tract Infection (URI)
|
16.7%
4/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Skin and subcutaneous tissue disorders
Photosensitivity Reaction/Erythema
|
0.00%
0/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
|
Skin and subcutaneous tissue disorders
Pruritis (Itching)
|
4.2%
1/24 • 1 year and 6 months
|
11.1%
3/27 • 1 year and 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
2/24 • 1 year and 6 months
|
7.4%
2/27 • 1 year and 6 months
|
Additional Information
Dr. Michael D. Roth
University of California, Los Angeles
Phone: 3102067389
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place