Interstitial Lung Disease, Scleroderma, Systemic
Conditions
Brief summary
A Phase II multi-center, double-blind, parallel group, randomized and placebo-controlled clinical trial addressing the treatment of patients with active and symptomatic Scleroderma-related interstitial lung disease (SSc-ILD).
Detailed description
A Phase II multi-center, double-blind, parallel group, randomized and placebo-controlled clinical trial addressing the treatment of patients with active and symptomatic Scleroderma-related interstitial lung disease (SSc-ILD). Patients who are either treatment naive or only recently started treatment (\</= 6 months of prior treatment) will be randomized in a 1:1 assignment to receive either oral mycophenolate mofetil (MMF) and a placebo (Plac) or a combination of oral MMF and oral pirfenidone (PFD), with both regimens administered for 18 months. The primary hypothesis is that the rapid onset and anti-fibrotic effects of PFD, which have been observed in the treatment of Idiopathic Pulmonary Fibrosis (IPF), will complement the delayed antiinflammatory and immunosuppressive effects of MMF, to produce a significantly more rapid and/or greater improvement in lung function over time than occurs in patients receiving control therapy with MMF and Plac.
Interventions
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).
DRUGPlacebo (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).
DRUGMycophenolate 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).
Sponsors
University of Michigan
Genentech, Inc.
University of California, Los Angeles
Michael Roth
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 yrs 2. Scleroderma as determined by the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. 3. Grade ≥2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index 4. FVC-% of ≤85% at screening 5. Onset of the first non-Raynaud manifestation of SSc within the prior 84 months. 6. Presence of any ground-glass opacification (GGO) on thoracic high-resolution computed tomography (HRCT) 7. Repeat FVC-% at the baseline visit within 10% of the FVC-% value measured at screening. If these criteria are not met, a repeat FVC-% may be obtained within 7 days and the subject may qualify for randomization if the repeat FVC-% agrees within 10% of the FVC-% obtained at screening.
Exclusion criteria
1. Disease features supporting the primary diagnosis of another connective tissue disease such as rheumatoid arthritis, systemic lupus erythematosus or mixed connective tissue disease (Features consistent with a secondary Sjogren syndrome or scleroderma-associated myopathy will be allowed). 2. FVC-% of \<45% at either screening or baseline. 3. Forced Expiratory Volume in the first second (FEV1)/Forced Vital Capacity (FVC) ratio \<0.65 at either screening or baseline. 4. Diffusing capacity of the lung for carbon monoxide adjusted for hemoglobin, expressed as a percentage of the normal predicted value (DLCOHb-%) of \<30% at screening or \<25% at baseline. a) All participants with a DLCOHb-% between 30 to 40% must have pulmonary artery pressures documented by either echocardiogram, right heart catheterization or magnetic resonance imaging in order to be considered for inclusion. 5. Diagnosis of clinically significant resting pulmonary hypertension requiring treatment or mild pulmonary hypertension requiring treatment with more than one oral medication as ascertained prior to study evaluation or as part of a standard of care clinical assessment performed outside of the study protocol. 6. Evidence of uncontrolled congestive heart failure, unstable ischemic heart disease, history of complicated pulmonary embolism impacting on heart or lung function, or unstable cardiac arrhythmia requiring chronic anticoagulation. 7. Clinically significant abnormalities on HRCT not attributable to SSc 8. Hematologic abnormality at screening including: 1. Leukopenia (white blood cells \[WBC\] \<4.0x10\^3/µl). 2. Thrombocytopenia (platelet count \<120.0x10\^3/µl). 3. Clinically significant anemia \[Hemoglobin (Hgb) \<10.0 g/dl\]. Participants with an identified and correctable etiology may be eligible if repeat testing within the maximal 90-day screening period meets all criteria. 9. A diagnosis of chronic liver disease or abnormal baseline liver function test (LFTs) or total bilirubin that are \>2.0 x upper normal limit 10. Serum creatinine \>2.0mg/dl 11. History of recurrent aspiration, uncontrolled heartburn, or gastroesophageal reflux disease (GERD) with a reflux scale score of \>1.00 as determined by a UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Scale (UCLA SCTC GIT), Version 2.0. Participants with uncontrolled heartburn or GERD that is amenable to medical management may be eligible if repeat testing within the maximal 90-day screening period meets this criteria. 12. Known achalasia, esophageal stricture or esophageal dysfunction sufficient to limit the ability to swallow medication. 13. Pregnancy (as documented by blood test) and/or breast feeding 14. If of child bearing potential (a female participant \< 55 years of age who has not been postmenopausal for ≥ 5 years or who has not had a bilateral salpingectomy, hysterectomy and/or oophorectomy), failure to employ two reliable means of contraception which may include surgical sterilization, barrier methods, spermicides, intrauterine devices, and/or hormonal contraception, unless the participant chooses abstinence (to avoid heterosexual intercourse completely). If a subject chooses abstinence, then a second reliable means of contraception is not needed. 15. Prior use of potential disease modifying antirheumatic drugs (DMARDs) according to the following exposure rules: 1. Use of oral cyclophosphamide (CYC), MMF, azathioprine or other oral or short half-life DMARDs (as detailed in Protocol Section 7.5.1a) for more than 6 months in the past year as determined at the time of the initial screening visit. 2. Treatment with more than three intravenous doses of CYC, one treatment course of Rituximab or other intravenous or injectable DMARDs (as detailed in Protocol Section 7.5.1b) in the past year. 3. More distant history of treatment with a DMARD is allowed as long as the patient has a new diagnosis/new episode of active SSc-ILD since stopping that treatment and meets the criteria noted in 15a or 15b. 16. Use of CYC, MMF, azathioprine, Rituximab or other DMARD (as defined in Protocol Section 7.5.1a&b) in the 30 days prior to their baseline visit unless the patient is on MMF and the responsible physician indicates that continued use is in the best clinical interest of the patient. 17. Active infection (lung, ulcers or elsewhere) whose management would be compromised by immunosuppression. 18. Other serious concomitant medical illness (e.g., active malignancy within the past 5 years other than surgically-removed local skin cancer such as a basal cell carcinoma), chronic debilitating illness (other than SSc), unreliability or drug abuse that might compromise the patient's participation in the trial. 19. Current use, or use within the 30 days prior to their baseline visit, of prednisone (or equivalent) in doses \>10 mg/day. 20. Smoking of cigars, pipes, or cigarettes during the past 6 months. 21. Use of contraindicated medications, including medications with putative disease-modifying properties that do not meet the exposure limits described in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Predicted Forced Vital Capacity (FVC-%) | Baseline to 18 months | 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-%). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Modified Rodnan Skin Score (mRSS) | Baseline to 18 months | 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. |
| Forced Vital Capacity Volume (FVC, in ml) | Baseline to 18 months | Change from baseline to month 18 in the Forced Vital Capacity volume (FVC, in ml) |
| Mahler Modified Transitional Dyspnea Index (TDI) | Baseline to 18 months | 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). |
| Health Assessment Questionnaire Modified for Scleroderma (HAQ-DI) | Baseline to 18 months | 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). |
| St. George's Respiratory Questionnaire (SGRQ) | Baseline to 18 months | 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). |
| High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Whole Lung (QLF-WL) | Screening to 18 months | 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. |
| High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Lobe of Maximal Involvement (QLF-LM) | Screening to 18 months | 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. |
| High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL) | Screening to 18 months | 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. |
| High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Lobe of Maximal Involvement (QILD-LM) | Screening to 18 months | 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. |
| High Resolution Computerized Tomography (HRCT) Measures of Total Lung Capacity (TLC) | Screening to 18 months | Change from screening to 18 months in quantitative HRCT measurement of TLC at maximal inspiration (HRCT-TLC). Higher scores indicates a better outcome. |
| Percent Predicted Single-breath Diffusing Capacity for Carbon Monoxide (DLCOHb-%) | Baseline to 18 months | 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-%). |
| Greater Than 5% Improvement in FVC-% | Baseline to 18 months | The percentage of subjects in each treatment arm achieving greater than a 5% improvement in FVC-% over the 18-month treatment period. |
| Percentage of Participants Achieving Specified Absolute Changes of FVC-% | Baseline to 18 months | 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. |
| Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Baseline to 18 months | 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. |
| Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders | Baseline to 18 months | 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. |
| Percentage of Participants Achieving Specified Absolute Changes of mRSS | Baseline to 18 months | 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. |
| Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | Baseline to 18 months | 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. |
| Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 18 months | 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. |
| Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | 18 months | 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. |
| Time to Withdrawal From the Study Drug or Treatment Failure | Baseline to 18 months | 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. |
| Number of Participants With Treatment-related Adverse Events as Assessed by System Organ Classification Using Preferred Medical Dictionary for Regulatory Activities (MedDRA) Terms. | Baseline to 18 months | 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. |
| 3.0% or Greater Improvement From Baseline in FVC-%. | Baseline to 18 months | 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. |
Countries
United States
Participant flow
Pre-assignment details
88 consented with 31 subsequently deemed ineligible, 6 withdrawals prior to randomization, resulting in 51 participants considered enrolled, eligible and randomized.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 24 |
| 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). | 27 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo (Plac) + Mycophenolate (MMF) | Total | Pirfenidone (PFD) + Mycophenolate (MMF) |
|---|---|---|---|
| Age, Continuous | 52.6 years STANDARD_DEVIATION 10 | 54.7 years STANDARD_DEVIATION 10.1 | 56.6 years STANDARD_DEVIATION 9.9 |
| Disease Duration | 32.9 months STANDARD_DEVIATION 24.2 | 30.8 months STANDARD_DEVIATION 24.7 | 28.9 months STANDARD_DEVIATION 25.4 |
| Forced Vital Capacity volume (FVC) | 2705 ml STANDARD_DEVIATION 540 | 2655 ml STANDARD_DEVIATION 674 | 2610 ml STANDARD_DEVIATION 781 |
| Health Assessment Questionnaire Disability Index (HAQ-DI) | 0.4 units on a scale STANDARD_DEVIATION 0.4 | 0.5 units on a scale STANDARD_DEVIATION 0.5 | 0.5 units on a scale STANDARD_DEVIATION 0.6 |
| Mahler Baseline Dyspnea Index | 6.8 units on a scale STANDARD_DEVIATION 1.5 | 6.9 units on a scale STANDARD_DEVIATION 1.8 | 6.9 units on a scale STANDARD_DEVIATION 2 |
| Modified Rodnan Skin Score (mRSS) | 8.1 units on a scale STANDARD_DEVIATION 7.6 | 10.0 units on a scale STANDARD_DEVIATION 9 | 11.7 units on a scale STANDARD_DEVIATION 9.9 |
| Percent predicted forced vital capacity (FVC-%) | 71.5 percent predicted STANDARD_DEVIATION 9.9 | 71.0 percent predicted STANDARD_DEVIATION 10.4 | 70.6 percent predicted STANDARD_DEVIATION 11 |
| Percent predicted single-breath diffusing capacity for carbon monoxide (DLCOHb-%) | 55.6 percent predicted STANDARD_DEVIATION 14.4 | 55.1 percent predicted STANDARD_DEVIATION 13 | 54.6 percent predicted STANDARD_DEVIATION 12 |
| Quantitative interstitial lung disease score in the lobe of maximal involvement (QILD-LM) | 42.0 percent STANDARD_DEVIATION 17.9 | 41.9 percent STANDARD_DEVIATION 18.6 | 41.8 percent STANDARD_DEVIATION 19.5 |
| Quantitative interstitial lung disease score in the whole lung (QILD-WL) | 24.1 percent STANDARD_DEVIATION 11.3 | 23.9 percent STANDARD_DEVIATION 11.4 | 23.8 percent STANDARD_DEVIATION 11.8 |
| Quantitative lung fibrosis score in the lobe of maximal involvement (QLF-LM) | 14.5 percent STANDARD_DEVIATION 14 | 15.4 percent STANDARD_DEVIATION 15.7 | 16.3 percent STANDARD_DEVIATION 17.4 |
| Quantitative lung fibrosis score in the whole lung (QLF-WL) | 6.0 percent STANDARD_DEVIATION 5.1 | 6.3 percent STANDARD_DEVIATION 5.5 | 6.5 percent STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 41 Participants | 22 Participants |
| Region of Enrollment United States | 24 participants | 51 participants | 27 participants |
| Scleroderma Classification Diffuse | 8 Participants | 21 Participants | 13 Participants |
| Scleroderma Classification Limited | 13 Participants | 24 Participants | 11 Participants |
| Scleroderma Classification Sine | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 17 Participants | 36 Participants | 19 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
| Total lung capacity (TLC) | 3859 ml STANDARD_DEVIATION 883 | 3783 ml STANDARD_DEVIATION 872 | 3717 ml STANDARD_DEVIATION 874 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 27 |
| other Total, other adverse events | 23 / 24 | 27 / 27 |
| serious Total, serious adverse events | 2 / 24 | 4 / 27 |
Outcome results
Primary
Percent Predicted Forced Vital Capacity (FVC-%)
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-%).
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percent Predicted Forced Vital Capacity (FVC-%) | 2.24 percent predicted | Standard Error 1.351 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percent Predicted Forced Vital Capacity (FVC-%) | 2.09 percent predicted | Standard Error 1.278 |
p-value: 0.9326Mixed Models Analysis
Other Pre-specified
3.0% or Greater Improvement From Baseline in FVC-%.
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.
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | 3.0% or Greater Improvement From Baseline in FVC-%. | 17.8 months |
| Pirfenidone (PFD) + Mycophenolate (MMF) | 3.0% or Greater Improvement From Baseline in FVC-%. | 12.3 months |
p-value: 0.3261Stratified log rank
Other Pre-specified
Forced Vital Capacity Volume (FVC, in ml)
Change from baseline to month 18 in the Forced Vital Capacity volume (FVC, in ml)
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Forced Vital Capacity Volume (FVC, in ml) | 121.53 ml | Standard Error 62.41 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Forced Vital Capacity Volume (FVC, in ml) | 112.33 ml | Standard Error 59.055 |
p-value: 0.8898Mixed Models Analysis
Other Pre-specified
Greater Than 5% Improvement in FVC-%
The percentage of subjects in each treatment arm achieving greater than a 5% improvement in FVC-% over the 18-month treatment period.
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Greater Than 5% Improvement in FVC-% | 6 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Greater Than 5% Improvement in FVC-% | 9 Participants |
p-value: 0.454Regression, Logistic
Other Pre-specified
Health Assessment Questionnaire Modified for Scleroderma (HAQ-DI)
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).
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Health Assessment Questionnaire Modified for Scleroderma (HAQ-DI) | -0.03 score on a scale | Standard Error 0.109 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Health Assessment Questionnaire Modified for Scleroderma (HAQ-DI) | -0.17 score on a scale | Standard Error 0.103 |
p-value: 0.2819Mixed Models Analysis
Other Pre-specified
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Lobe of Maximal Involvement (QILD-LM)
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.
Time frame: Screening to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | 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 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Lobe of Maximal Involvement (QILD-LM) | -0.99 percent | Standard Error 2.486 |
p-value: 0.1931ANCOVA
Other Pre-specified
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL)
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.
Time frame: Screening to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | 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 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Quantitative Interstitial Lung Disease Score in the Whole Lung (QILD-WL) | -1.15 percent | Standard Error 1.829 |
p-value: 0.1177ANCOVA
Other Pre-specified
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Lobe of Maximal Involvement (QLF-LM)
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.
Time frame: Screening to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | 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 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Lobe of Maximal Involvement (QLF-LM) | 0.13 percent | Standard Error 2.132 |
p-value: 0.3515ANCOVA
Other Pre-specified
High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Whole Lung (QLF-WL)
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.
Time frame: Screening to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Whole Lung (QLF-WL) | 1.46 percent | Standard Error 0.994 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Quantitative Lung Fibrosis Score in the Whole Lung (QLF-WL) | -0.11 percent | Standard Error 0.935 |
p-value: 0.1701ANCOVA
Other Pre-specified
High Resolution Computerized Tomography (HRCT) Measures of Total Lung Capacity (TLC)
Change from screening to 18 months in quantitative HRCT measurement of TLC at maximal inspiration (HRCT-TLC). Higher scores indicates a better outcome.
Time frame: Screening to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Total Lung Capacity (TLC) | 70.69 ml | Standard Error 78.986 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | High Resolution Computerized Tomography (HRCT) Measures of Total Lung Capacity (TLC) | 191.99 ml | Standard Error 73.738 |
p-value: 0.1811ANCOVA
Other Pre-specified
Mahler Modified Transitional Dyspnea Index (TDI)
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).
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Mahler Modified Transitional Dyspnea Index (TDI) | 1.13 score on a scale | Standard Error 0.754 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Mahler Modified Transitional Dyspnea Index (TDI) | 1.99 score on a scale | Standard Error 0.71 |
p-value: 0.3826Mixed Models Analysis
Other Pre-specified
Modified Rodnan Skin Score (mRSS)
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.
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Modified Rodnan Skin Score (mRSS) | -5.42 score on a scale | Standard Error 1.164 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Modified Rodnan Skin Score (mRSS) | -4.96 score on a scale | Standard Error 1.109 |
p-value: 0.7489Mixed Models Analysis
Other Pre-specified
Number of Participants With Treatment-related Adverse Events as Assessed by System Organ Classification Using Preferred Medical Dictionary for Regulatory Activities (MedDRA) Terms.
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.
Time frame: Baseline to 18 months
Population: Safety population includes all the randomized participants who received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | 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 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Number of Participants With Treatment-related Adverse Events as Assessed by System Organ Classification Using Preferred Medical Dictionary for Regulatory Activities (MedDRA) Terms. | 27 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified Absolute Changes of FVC-%
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.
Time frame: Baseline to 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | ≥ 5% to < 10% | 5 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | > -5% to ≤ 0% | 5 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | > 0% to < 5% | 10 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | > -10% to ≤ -5% | 1 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | ≥ 10% to < 15% | 1 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | > -10% to ≤ -5% | 2 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | ≥ 10% to < 15% | 1 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | ≥ 5% to < 10% | 8 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | > 0% to < 5% | 6 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% | > -5% to ≤ 0% | 6 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders
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.
Time frame: Baseline to 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders | Responder (> 0%) | 16 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders | Non-responder (≤ 0%) | 6 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders | Responder (> 0%) | 15 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Any Responders or Any Non-responders | Non-responder (≤ 0%) | 8 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders
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.
Time frame: Baseline to 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Positive responder (≥ 3%) | 8 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Stable (> -3 to < 3) | 10 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Negative responder (≤ -3%) | 4 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Positive responder (≥ 3%) | 11 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Stable (> -3 to < 3) | 8 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of FVC-% Defined as Positive or Negative Responders | Negative responder (≤ -3%) | 4 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified Absolute Changes of mRSS
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.
Time frame: Baseline to 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | -8 to -5 | 4 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | 0 | 3 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | -12 to -9 | 1 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | 1 to 4 | 1 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | -4 to -1 | 8 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | ≥ 5 | 1 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | ≤ -13 | 2 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | ≥ 5 | 0 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | ≤ -13 | 6 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | -12 to -9 | 0 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | -8 to -5 | 4 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | -4 to -1 | 9 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | 0 | 3 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS | 1 to 4 | 1 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased.
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.
Time frame: Baseline to 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | Worsening (change > 5) | 0 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | No Change (-5 ≤ change ≤ 5) | 15 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | Improvement (change < -5) | 5 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | Worsening (change > 5) | 0 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | No Change (-5 ≤ change ≤ 5) | 13 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified Absolute Changes of mRSS Defined as Improved, no Change and Decreased. | Improvement (change < -5) | 10 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months
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.
Time frame: 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 1 to 3 | 4 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | -3 to -1 | 6 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 4 to 6 | 1 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | -6 to -4 | 3 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 0 | 8 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | -9 to -7 | 1 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 7 to 9 | 0 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | -9 to -7 | 4 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 7 to 9 | 0 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 4 to 6 | 1 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 1 to 3 | 5 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | 0 | 8 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | -3 to -1 | 2 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months | -6 to -4 | 5 Participants |
Other Pre-specified
Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration
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.
Time frame: 18 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | Worsening (change < 0) | 5 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | No Change (change = 0) | 8 Participants |
| Placebo (Plac) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | Improvement (change > 0) | 10 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | Worsening (change < 0) | 6 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | No Change (change = 0) | 8 Participants |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percentage of Participants Achieving Specified TDI Focal Score at 18 Months Defined as Improved, no Change or Deterioration | Improvement (change > 0) | 11 Participants |
Other Pre-specified
Percent Predicted Single-breath Diffusing Capacity for Carbon Monoxide (DLCOHb-%)
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-%).
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Percent Predicted Single-breath Diffusing Capacity for Carbon Monoxide (DLCOHb-%) | 1.25 percent predicted | Standard Error 1.549 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Percent Predicted Single-breath Diffusing Capacity for Carbon Monoxide (DLCOHb-%) | 1.24 percent predicted | Standard Error 1.505 |
p-value: 0.9968Mixed Models Analysis
Other Pre-specified
St. George's Respiratory Questionnaire (SGRQ)
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).
Time frame: Baseline to 18 months
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | St. George's Respiratory Questionnaire (SGRQ) | -4.77 score on a scale | Standard Error 3.487 |
| Pirfenidone (PFD) + Mycophenolate (MMF) | St. George's Respiratory Questionnaire (SGRQ) | -6.11 score on a scale | Standard Error 3.212 |
p-value: 0.7534Mixed Models Analysis
Other Pre-specified
Time to Withdrawal From the Study Drug or Treatment Failure
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.
Time frame: Baseline to 18 months
Population: Safety population includes all the randomized participants who received at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (Plac) + Mycophenolate (MMF) | Time to Withdrawal From the Study Drug or Treatment Failure | NA days |
| Pirfenidone (PFD) + Mycophenolate (MMF) | Time to Withdrawal From the Study Drug or Treatment Failure | NA days |