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

Primary Purpose

Systemic Sclerosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pirfenidone
Sponsored by
Genentech, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Systemic Sclerosis focused on measuring pirfenidone, SSc-ILD, scleroderma, systemic sclerosis, interstitial lung disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic, Scottsdale
  • University of California, Los Angeles
  • Stanford University School of Medicine
  • University of California, San Francisco
  • National Jewish Medical and Research Center
  • Georgetown University Hospital
  • Northwestern University, Chicago
  • Boston University Medical Center
  • University of Michigan
  • Hospital for Special Surgery
  • Columbia University
  • University of Cincinnati
  • Cleveland Clinic Foundation
  • University of Toledo
  • University of Pittsburgh Medical Center
  • Medical University South Carolina
  • University of Texas, Houston
  • University of Utah
  • St. Joseph's Healthcare
  • Toronto General Hospital
  • Università di Torino
  • University of Florence

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Pirfenidone: 4-Week Titration Group

Pirfenidone: 2-Week Titration Group

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.

Full Information

First Posted
August 23, 2013
Last Updated
July 6, 2016
Sponsor
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01933334
Brief Title
Safety and Tolerability of Pirfenidone in Participants With Systemic Sclerosis-Related Interstitial Lung Disease (SSc-ILD) (LOTUSS)
Acronym
LOTUSS
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 Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Sclerosis
Keywords
pirfenidone, SSc-ILD, scleroderma, systemic sclerosis, interstitial lung disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pirfenidone: 4-Week Titration Group
Arm Type
Experimental
Arm Description
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).
Arm Title
Pirfenidone: 2-Week Titration Group
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Pirfenidone
Intervention Description
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).
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment-Emergent Adverse Events (AEs)
Description
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.
Time Frame
From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Title
Percentage of Participants With Treatment-Emergent Serious Adverse Events (SAEs)
Description
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.
Time Frame
From baseline up to 28 days after the last dose of study drug (last dose = Week 16)
Secondary Outcome Measure Information:
Title
University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium (SCTC) Gastrointestinal Trial (GIT) Questionnaire Scale Scores
Description
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.
Time Frame
Baseline, Weeks 4, 8, 12, and 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
For additional information, call InterMune Medical Information Telephone: 1-888-486-6411
Organizational Affiliation
University of Cincinnati
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic, Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University School of Medicine
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
National Jewish Medical and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Northwestern University, Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Boston University Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Toledo
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
Medical University South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Texas, Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
St. Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 142
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 3L9
Country
Canada
Facility Name
Università di Torino
City
Orbassano
State/Province
Turin
ZIP/Postal Code
10043
Country
Italy
Facility Name
University of Florence
City
Firenze
ZIP/Postal Code
50139
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
7378088
Citation
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.
Results Reference
background
PubMed Identifier
27370878
Citation
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.
Results Reference
derived

Learn more about this trial

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

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