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

Phase 2

Completed

• Conditions: Systemic Sclerosis
• Interventions: Drug: Pirfenidone

• Registration Number: NCT01933334
• Lead Sponsor: Genentech, Inc.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-08-23
• Study First Submitted QC: 2013-08-28
• Study First Posted: 2013-09-02
• Study Start: 2013-10
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Results First Submitted: 2015-08-25
• Results First Submitted QC: 2015-08-25
• Results First Posted: 2015-09-28
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-06
• Last Update Posted: 2016-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

1. 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
2. Diagnosis of SSc-ILD based on an high-resolution computed tomography (HRCT) scan
3. 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
4. At study entry, the participant either was not taking SSc-ILD medication or was taking cyclophosphamide or mycophenolate

Exclusion Criteria

1. Clinically significant pulmonary hypertension
2. Known underlying liver disease
3. Clinical evidence of significant aspiration or uncontrolled gastroesophageal reflux
4. History of clinically significant asthma or chronic obstructive pulmonary disease
5. Active infection
6. Diagnosis of another connective tissue disorder
7. Evidence of a malignancy that is likely to result in significant disability or require significant medical or surgical intervention
8. History of unstable or deteriorating cardiac or pulmonary disease (other than SSc-ILD)
9. Pregnancy or lactation
10. Creatinine clearance <40 milliliters per minute (mL/min)
11. Prior use of pirfenidone
12. Unsuitable for enrollment or unlikely to comply with study requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pirfenidone: 4-Week Titration Group	Pirfenidone	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).
Pirfenidone: 2-Week Titration Group	Pirfenidone	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).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)	From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	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.
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)	From baseline up to 28 days after the last dose of study drug (last dose = Week 16)	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.

Secondary Outcome Measures

Name	Time	Method
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores	Baseline, Weeks 4, 8, 12, and 16	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.

Trial Locations

Locations (22)

University of Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Northwestern University, Chicago; 🇺🇸 Chicago, Illinois, United States

Boston University Medical Center; 🇺🇸 Boston, Massachusetts, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Stanford University School of Medicine; 🇺🇸 Redwood City, California, United States

National Jewish Medical and Research Center; 🇺🇸 Denver, Colorado, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Hospital for Special Surgery; 🇺🇸 New York, New York, United States

Columbia University; 🇺🇸 New York, New York, United States

University of Toledo; 🇺🇸 Toledo, Ohio, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas, Houston; 🇺🇸 Houston, Texas, United States

Medical University South Carolina; 🇺🇸 Charleston, South Carolina, United States

St. Joseph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada

Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

University of Florence; 🇮🇹 Firenze, Italy

Università di Torino; 🇮🇹 Orbassano, Turin, Italy

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Mayo Clinic, Scottsdale; 🇺🇸 Scottsdale, Arizona, United States