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

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)

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).

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: Pirfenidone

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 142
      • St. Joseph's Healthcare
    • Toronto, Ontario, Canada, M5T 3L9
      • Toronto General Hospital
• Italy
  • Firenze, Italy, 50139
    • University of Florence
  • Turin
    • Orbassano, Turin, Italy, 10043
      • Università di Torino
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic, Scottsdale
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Redwood City, California, United States, 94063
      • Stanford University School of Medicine
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University, Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10021
      • Hospital for Special Surgery
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pirfenidone: 4-Week Titration Group; 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; 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).
Experimental: Pirfenidone: 2-Week Titration Group; 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; 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).

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

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Chair: For additional information, call InterMune Medical Information Telephone: 1-888-486-6411, University of Cincinnati

Publications and helpful links

General Publications

• Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980 May;23(5):581-90. doi: 10.1002/art.1780230510.
• Khanna D, Albera C, Fischer A, Khalidi N, Raghu G, Chung L, Chen D, Schiopu E, Tagliaferri M, Seibold JR, Gorina E. An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial. J Rheumatol. 2016 Sep;43(9):1672-9. doi: 10.3899/jrheum.151322. Epub 2016 Jul 1.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: August 23, 2013
• First Submitted That Met QC Criteria: August 28, 2013
• First Posted (Estimate): September 2, 2013

Study Record Updates

• Last Update Posted (Estimate): August 4, 2016
• Last Update Submitted That Met QC Criteria: July 6, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: interstitial lung disease; systemic sclerosis; scleroderma; pirfenidone; SSc-ILD
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Sclerosis; Lung Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Lung Diseases, Interstitial; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: PSSc-001