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

NCT01933334 | Completed Phase 2 Results DMC

• 1 other identifier: PSSc-001
• Study Type: interventional
• Target: 63
• Locations: 3 countries
• Sites: 22

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).

Conditions

Systemic Sclerosis

Keywords

pirfenidone; SSc-ILD; scleroderma; systemic sclerosis; interstitial lung disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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

Study Arms (2)

Pirfenidone: 4-Week Titration Group

EXPERIMENTAL

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: 2-Week Titration Group

EXPERIMENTAL

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

Interventions

Pirfenidone DRUG

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).

Pirfenidone: 2-Week Titration Group; Pirfenidone: 4-Week Titration Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (22)

Mayo Clinic, Scottsdale

Scottsdale, Arizona, 85259, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University School of Medicine

Redwood City, California, 94063, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University, Chicago

Chicago, Illinois, 60611, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas, Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

St. Joseph's Healthcare

Hamilton, Ontario, L8N 142, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5T 3L9, Canada

Location

Università di Torino

Orbassano, Turin, 10043, Italy

Location

University of Florence

Florence, 50139, Italy

Location

Related Publications (2)

• 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.

  PMID: 7378088 BACKGROUND

• 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.

  PMID: 27370878 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse; Lung Diseases, Interstitial

Interventions

pirfenidone

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• For additional information, call InterMune Medical Information Telephone: 1-888-486-6411

  University of Cincinnati

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: September 2, 2013
• Study Start: October 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: August 4, 2016
• Results First Posted: September 28, 2015

Record last verified: 2016-07

Locations

US (18); CA (2); IT (2)