Safety and Tolerability of Pirfenidone in Participants With Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD) (LOTUSS)

Study Overview
=================
Brief Summary
-----------------
PSSc-001 (LOTUSS) This study is a Phase 2, multinational, open-label, randomized, parallel-group, safety and tolerability study of pirfenidone in participants with systemic sclerosis-related interstitial lung disease (SSc-ILD).

Official Title
-----------------
The LOTUSS Trial: An Open-Label, Randomized, Phase 2 Study of the Safety and Tolerability of Pirfenidone When Administered to Patients With Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD) (LOTUSS)

Conditions
-----------------
Systemic Sclerosis

Intervention / Treatment
-----------------
* Drug: Pirfenidone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of systemic sclerosis-related (SSc) confirmed by the American College of Rheumatology classification criteria of systemic sclerosis (Masi 1980); duration of diagnosis less than (<) 7 years Diagnosis of SSc-ILD based on an high-resolution computed tomography (HRCT) scan Screening forced vital capacity (FVC) greater than equal to (>=) 50 percent (%) of the predicted value, and screening carbon monoxide diffusing capacity (DLCO) >=40% of the predicted value At study entry, the participant either was not taking SSc-ILD medication or was taking cyclophosphamide or mycophenolate Exclusion Criteria: Clinically significant pulmonary hypertension Known underlying liver disease Clinical evidence of significant aspiration or uncontrolled gastroesophageal reflux History of clinically significant asthma or chronic obstructive pulmonary disease Active infection Diagnosis of another connective tissue disorder Evidence of a malignancy that is likely to result in significant disability or require significant medical or surgical intervention History of unstable or deteriorating cardiac or pulmonary disease (other than SSc-ILD) Pregnancy or lactation Creatinine clearance <40 milliliters per minute (mL/min) Prior use of pirfenidone Unsuitable for enrollment or unlikely to comply with study requirements

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pirfenidone: 4-Week Titration Group<br>Participants will receive one 267 milligrams (mg) oral pirfenidone capsule three times daily (TID) (801 mg per day [mg/day]) for 2 weeks followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 2 weeks (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 12 weeks maintenance period). | Drug: Pirfenidone<br>* Pirfenidone will be administered orally at a dose of 267 mg one oral capsule TID (801 mg/day) for 1 or 2 weeks followed by two 267 mg oral capsules TID (1602 mg/day) for 1 or 2 weeks (titration period) and then three 267 mg oral capsules TID (2403 mg/day) for 12 weeks (maintenance period).<br>|
| Experimental: Pirfenidone: 2-Week Titration Group<br>Participants will receive one 267 mg oral pirfenidone capsule TID (801 mg/day) for 1 week followed by two 267 mg oral pirfenidone capsules TID (1602 mg/day) for 1 week (titration period) and then three 267 mg oral pirfenidone capsules TID (2403 mg/day) for 14 weeks (maintenance period). | Drug: Pirfenidone<br>* Pirfenidone will be administered orally at a dose of 267 mg one oral capsule TID (801 mg/day) for 1 or 2 weeks followed by two 267 mg oral capsules TID (1602 mg/day) for 1 or 2 weeks (titration period) and then three 267 mg oral capsules TID (2403 mg/day) for 12 weeks (maintenance period).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (AEs) | Percentage of participants who had treatment-emergent AEs, defined as newly occurring or worsening after first dose. Relatedness to (study drug) was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. | From baseline up to 28 days after the last dose of study drug (last dose = Week 16) | 
| Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | From baseline up to 28 days after the last dose of study drug (last dose = Week 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores | UCLA SCTC GIT Scale 2.0 is a 34-item self-administered questionnaire to obtain participant's assessment of the frequency of GI symptoms in preceding 7 days and how symptoms affected his/her life. All but 2 items were scored on a 0 to 3 scale (0=better health, 3=worse health); remaining 2 items were scored as 0 (better health) and 1 (worse health). The 34 items are divided into seven scales (reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being, and constipation). Individual scale score was calculated as the average of the items in the scale. Individual scale score ranged from 0 to 3 for reflux, distention/bloating, fecal soilage, social functioning, and emotional well-being; 0 to 2 for diarrhea; and 0 to 2.5 for constipation. A total score was also calculated as the average of 6 of the 7 scales (omitting constipation) and ranged from 0 to 2.83. For individual and total scores 0 indicated better health and higher score indicates worse health. | Baseline, Weeks 4, 8, 12, and 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pirfenidone, SSc-ILD, scleroderma, systemic sclerosis, interstitial lung disease