Scleroderma Lung Study III - Combining Pirfenidone With M... | NCT03221257

NCT03221257

Status Module

Sponsor/Collaborators Module

Name	Class
University of Michigan	OTHER
Genentech, Inc.	INDUSTRY
University of California, Los Angeles	OTHER

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo (Plac) + Mycophenolate (MMF)	Placebo Comparator	Participants will receive Placebo (Plac) as add-on to a background therapy of Mycophenolate Mofetil (MMF).	Drug: Placebo (Plac) Drug: Mycophenolate Mofetil (MMF)
Pirfenidone (PFD) + Mycophenolate (MMF)	Experimental	Participants will receive Pirfenidone (PFD) as add-on to a background therapy of Mycophenolate Mofetil (MMF).	Drug: Pirfenidone (PFD) Drug: Mycophenolate Mofetil (MMF)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pirfenidone (PFD)	Drug	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).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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-%).	Baseline to 18 months

Other Outcomes

Measure	Description	Time Frame
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-%).	Baseline to 18 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 yrs
Scleroderma as determined by the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
Grade ≥2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index
FVC-% of ≤85% at screening
Onset of the first non-Raynaud manifestation of SSc within the prior 84 months.
Presence of any ground-glass opacification (GGO) on thoracic high-resolution computed tomography (HRCT)
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:

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).
FVC-% of <45% at either screening or baseline.
Forced Expiratory Volume in the first second (FEV1)/Forced Vital Capacity (FVC) ratio <0.65 at either screening or baseline.
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.
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.
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.
Clinically significant abnormalities on HRCT not attributable to SSc
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.
A diagnosis of chronic liver disease or abnormal baseline liver function test (LFTs) or total bilirubin that are >2.0 x upper normal limit
Serum creatinine >2.0mg/dl
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.
Known achalasia, esophageal stricture or esophageal dysfunction sufficient to limit the ability to swallow medication.
Pregnancy (as documented by blood test) and/or breast feeding
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.
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.
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.
Active infection (lung, ulcers or elsewhere) whose management would be compromised by immunosuppression.
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.
Current use, or use within the 30 days prior to their baseline visit, of prednisone (or equivalent) in doses >10 mg/day.
Smoking of cigars, pipes, or cigarettes during the past 6 months.
Use of contraindicated medications, including medications with putative disease-modifying properties that do not meet the exposure limits described in Exclusion Criteria #15 and #16, moderate or strong inhibitors of cytochrome P450 (CYP) isozyme 1A2 (CYP1A2) (note ciprofloxacin allowed up to a dose of 500 mg twice daily), and moderate inducers of CYP1A2 (such as tobacco smoke or phenytoin). See Protocol Section 7.5 for complete list.

Contacts/Locations Module

Name	Affiliation	Role
Michael D Roth, MD	Pulmonary & Critical Care Medicine, Geffen School of Medicine at UCLA	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California Los Angeles		Los Angeles	California	90095	United States
University of Colorado

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27469583	Background	Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM; Sclerodema Lung Study II Investigators. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016 Sep;4(9):708-719. doi: 10.1016/S2213-2600(16)30152-7. Epub 2016 Jul 25.
28012804

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_ICF	Yes	No	Yes	Study Protocol and Informed Consent Form	Nov 17, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Pirfenidone (PFD) + Mycophenolate (MMF)

Safety population includes all the randomized participants who received at least one dose of study medication.

Arm/Group Information

ID	Title	Description
BG000	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).
BG001	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).
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0002.24± 1.351 OG0012.09± 1.278

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		0.9326		Mean Difference (Net)	-0.14			2-Sided								Superiority

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-%).

Posted

Least Squares Mean

Standard Error

percent predicted

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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)

Posted

Least Squares Mean

Standard Error

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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).

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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).

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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).

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Least Squares Mean

Standard Error

percent

Screening to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Least Squares Mean

Standard Error

percent

Screening to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Least Squares Mean

Standard Error

percent

Screening to 18 months

ID	Title	Description
OG000	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).
OG001	Pirfenidone (PFD) + Mycophenolate (MMF)

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.

Posted

Least Squares Mean

Standard Error

percent

Screening to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Least Squares Mean

Standard Error

Screening to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Median

95% Confidence Interval

months

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

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).

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

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).

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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 \

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).

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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 (\

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).

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

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).

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

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).

Posted

Count of Participants

Participants

18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

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).

Posted

Count of Participants

Participants

18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Safety population includes all the randomized participants who received at least one dose of study medication.

Posted

Median

95% Confidence Interval

days

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

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.

Safety population includes all the randomized participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Baseline to 18 months

ID	Title	Description
OG000	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).
OG001	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).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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).	0	24	2	24	23	24
EG001	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).	0	27	4	27	27	27

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Right Sided Chest Pain	Cardiac disorders	Systematic Assessment	EG0000 affected24 at risk EG0011 affected27 at risk
Colitis	Gastrointestinal disorders	Systematic Assessment	EG0001 affected24 at risk EG0010 affected27 at risk
Covid-19 Infection	Infections and infestations	Systematic Assessment	EG0001 affected24 at risk EG0010 affected27 at risk
Herpes Zoster Ophthalmicus	Infections and infestations	Systematic Assessment	EG0000 affected24 at risk EG0011 affected27 at risk
Basal Cell Carcinoma, Nodular	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected24 at risk EG0011 affected27 at risk
Extra-nodal Marginal Zone B-cell Lymphoma of the Stomach and Antrum	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 affected24 at risk EG0011 affected27 at risk
Scleroderma Renal Crisis	Renal and urinary disorders	Systematic Assessment	EG0000 affected24 at risk EG0011 affected27 at risk
Acute Chronic Hypoxemic Respiratory Failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 affected24 at risk EG0010 affected27 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected24 at risk EG0011 affected27 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 affected24 at risk EG0011 affected27 at risk
Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 affected24 at risk EG0010 affected27 at risk
Chest Pain (Cardiac)	Cardiac disorders	Systematic Assessment	EG0002 affected24 at risk EG0010 affected27 at risk
Dry Eyes	Eye disorders	Systematic Assessment	EG0004 affected24 at risk EG0010 affected27 at risk
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0005 affected24 at risk EG0014 affected27 at risk
Bloating	Gastrointestinal disorders	Systematic Assessment	EG0001 affected24 at risk EG0013 affected27 at risk
Blood in Stool	Gastrointestinal disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0002 affected24 at risk EG0012 affected27 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG00010 affected24 at risk EG00112 affected27 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0002 affected24 at risk EG0012 affected27 at risk
Gastro-esophageal Reflux Disease (GERD)	Gastrointestinal disorders	Systematic Assessment	EG0002 affected24 at risk EG0012 affected27 at risk
Heartburn	Gastrointestinal disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
Loose Stools	Gastrointestinal disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Loss of Appetite	Gastrointestinal disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0007 affected24 at risk EG00122 affected27 at risk
Stomach Pain	Gastrointestinal disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
Upset Stomach	Gastrointestinal disorders	Systematic Assessment	EG0002 affected24 at risk EG0011 affected27 at risk
Vomiting (Emesis)	Gastrointestinal disorders	Systematic Assessment	EG0004 affected24 at risk EG00111 affected27 at risk
Worsening GERD	Gastrointestinal disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Dizziness	General disorders	Systematic Assessment	EG0001 affected24 at risk EG0015 affected27 at risk
Fatigue	General disorders	Systematic Assessment	EG0005 affected24 at risk EG0018 affected27 at risk
Fever	General disorders	Systematic Assessment	EG0003 affected24 at risk EG0010 affected27 at risk
Headache	General disorders	Systematic Assessment	EG0005 affected24 at risk EG0016 affected27 at risk
Insomnia	General disorders	Systematic Assessment	EG0001 affected24 at risk EG0014 affected27 at risk
ALT Increased	Hepatobiliary disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
COVID-19	Infections and infestations	Systematic Assessment	EG0000 affected24 at risk EG0014 affected27 at risk
Sinusitis	Infections and infestations	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Upper Respiratory Tract Infection (URI)	Infections and infestations	Systematic Assessment	EG0002 affected24 at risk EG0012 affected27 at risk
Urinary Tract Infection (UTI)	Infections and infestations	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Yeast Infection	Infections and infestations	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Weight Loss	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected24 at risk EG0013 affected27 at risk
Back Pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0002 affected24 at risk EG0012 affected27 at risk
Joint Pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0003 affected24 at risk EG0012 affected27 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
Tremors	Nervous system disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Anxiety	Psychiatric disorders	Systematic Assessment	EG0002 affected24 at risk EG0013 affected27 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
Urinary Tract Infection (UTI)	Renal and urinary disorders	Systematic Assessment	EG0001 affected24 at risk EG0012 affected27 at risk
Bronchitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected24 at risk EG0010 affected27 at risk
Cold	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected24 at risk EG0011 affected27 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0005 affected24 at risk EG0017 affected27 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected24 at risk EG0011 affected27 at risk
Shortness of Breath	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Upper Respiratory Tract Infection (URI)	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 affected24 at risk EG0012 affected27 at risk
Photosensitivity Reaction/Erythema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected24 at risk EG0012 affected27 at risk
Pruritis (Itching)	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected24 at risk EG0013 affected27 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 affected24 at risk EG0012 affected27 at risk

Only 51 (34%) of our planned recruitment goal of 150 were randomized. During the recruitment period MMF became a standard of care for treatment in early systemic sclerosis (SSc)-ILD, including the treatment of both lung and skin disease, thereby increasing the difficulty in recruiting treatment-naïve patients. Other barriers to recruitment included the Coronavirus Disease 2019 (COVID-19) epidemic and FDA approval of nintedanib as an alternative treatment during the initial phase of the trial.

Certain Agreements

First MCP Posted Date

ID	Term
D012595	Scleroderma, Systemic
D017563	Lung Diseases, Interstitial

ID	Term
C093844	pirfenidone
C008758	5'-palmitoyl cytarabine
D009173	Mycophenolic Acid
D016568	Drugs, Generic

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).

ID	Term
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D012871	Skin Diseases
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D005227	Fatty Acids
D008055	Lipids
D004364	Pharmaceutical Preparations