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

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ClinicalTrials.gov Identifier: NCT01933334

Recruitment Status : Completed

First Posted : September 2, 2013

Results First Posted : September 28, 2015

Last Update Posted : August 4, 2016

Sponsor:

Information provided by (Responsible Party):

Genentech, Inc.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Systemic Sclerosis	Drug: Pirfenidone	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	63 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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)
Study Start Date :	October 2013
Actual Primary Completion Date :	September 2014
Actual Study Completion Date :	September 2014

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Pulmonary alveolar microlithiasis Systemic scleroderma

MedlinePlus related topics: Interstitial Lung Diseases Lung Diseases Scleroderma

Drug Information available for: Pirfenidone

Genetic and Rare Diseases Information Center resources: Systemic Scleroderma

U.S. FDA Resources

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

Percentage of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: 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.
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs) [ Time Frame: 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.

Secondary Outcome Measures :

University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01933334

Locations

Show 22 study locations

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

Sponsors and Collaborators

Genentech, Inc.

Investigators

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Study Chair:	For additional information, call InterMune Medical Information Telephone: 1-888-486-6411	University of Cincinnati

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Genentech, Inc.
ClinicalTrials.gov Identifier:	NCT01933334
Other Study ID Numbers:	PSSc-001
First Posted:	September 2, 2013 Key Record Dates
Results First Posted:	September 28, 2015
Last Update Posted:	August 4, 2016
Last Verified:	July 2016

Keywords provided by Genentech, Inc.:


pirfenidone SSc-ILD scleroderma systemic sclerosis interstitial lung disease

Additional relevant MeSH terms:

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Lung Diseases Lung Diseases, Interstitial Scleroderma, Systemic Scleroderma, Diffuse Sclerosis Pathologic Processes Respiratory Tract Diseases Connective Tissue Diseases Skin Diseases Pirfenidone	Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Anti-Inflammatory Agents Antirheumatic Agents Antineoplastic Agents

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