Pirfenidone as Treatment of Skin Fibrosis in Systemic Sclerosis

• ClinicalTrials.gov Identifier: NCT03068234
• Recruitment Status: Unknown
• First Posted: March 1, 2017
• Last Update Posted: March 1, 2017
• Sponsor: RenJi Hospital
• Information provided by (Responsible Party): RenJi Hospital

Study Description

Brief Summary:

This study is to evaluate the efficacy and safety of an antifibrotic agent, pirfenidone as treatment of systemic sclerosis. The primary outcome of this study is improvement of skin fibrosis.

Condition or disease	Intervention/treatment	Phase
Systemic Sclerosis	Drug: Pirfenidone; Drug: Placebo oral capsule; Drug: Steroids	Phase 2; Phase 3

Detailed Description:

All patients enrolled should suffer from moderate to severe skin fibrosis at the screening stage.

The study period is 52 week. The study contains two stages, a 24-week blind stage following with open stage for another 24-week period of time. Subjects will receive pirfenidone or placebo randomized in the first 24-week and will all receive pirfenidone treatment in the second 24-week, with of combination of low dose steroids.

The secondary outcomes of this study include but not limit to safety, improvement of lung fibrosis and digital ulcer burden.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blinded, Placebo Controlled Study to Evaluate Clinical Efficacy and Safety of Pirfenidone for Skin Fibrosis in Systemic Sclerosis
• Estimated Study Start Date: May 2017
• Estimated Primary Completion Date: April 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pirfenidone group; The subjects will receive pirfenidone from 200mg three times a day, oral administrated, with low dose steroids.	Drug: Pirfenidone; A chemical synthesized agent showing anti-fibrotic effects in idiopathic pulmonary fibrosis.; Drug: Steroids; Low dose of glucocorticoids, a basic treatment for patients with systemic sclerosis
Placebo Comparator: Control group; The subjects will receive placebo within first 24-week, and pirfenidone 200mg three times a day for the second 24-week, with low dose steroids.	Drug: Pirfenidone; A chemical synthesized agent showing anti-fibrotic effects in idiopathic pulmonary fibrosis.; Drug: Placebo oral capsule; Placebo for pirfenidone capsule; Drug: Steroids; Low dose of glucocorticoids, a basic treatment for patients with systemic sclerosis

Outcome Measures

Primary Outcome Measures :

1. Modified Rodnan Skin Score (mRSS） [ Time Frame: Week 52 ]
   A semi-quantitative score for skin fibrosis of every subjects

Secondary Outcome Measures :

1. Modified Rodnan Skin Score [ Time Frame: Week 24 ]
   A semi-quantitative score for skin fibrosis of every subjects
2. Assessment of chest CT [ Time Frame: Week 52 ]
   Semi-quantitative scale for fibrotic changes in chest CT images from an individual patient
3. Assessment of chest CT [ Time Frame: Week 24 ]
   Semi-quantitative scale for fibrotic changes in chest CT images from an individual patient
4. Forced vital capacity [ Time Frame: Week 52 ]
   A marker for lung function that may decrease with pulmonary fibrosis
5. Forced vital capacity [ Time Frame: Week 24 ]
   A marker for lung function that may decrease with pulmonary fibrosis
6. Diffusing capacity [ Time Frame: Week 52 ]
   Another marker for lung function that may decrease with pulmonary fibrosis
7. Diffusing capacity [ Time Frame: Week 24 ]
   Another marker for lung function that may decrease with pulmonary fibrosis
8. 6 minute walk test [ Time Frame: Week 52 ]
   A simple, well-accepted and quantitative clinical exam to test heart and lung function
9. 6 minute walk test [ Time Frame: Week 24 ]
   A simple, well-accepted and quantitative clinical exam to test heart and lung function
10. Hand function assessment [ Time Frame: Week 52 ]
    Hand function will be measured by Cochin Hand Function Scale
11. Hand function assessment [ Time Frame: Week 24 ]
    Hand function will be measured by Cochin Hand Function Scale
12. Proportion of subjects with increased mRSS [ Time Frame: Week 52 ]
    Proportion of subjects with ∆mRSS≥5
13. Proportion of subjects with increased mRSS [ Time Frame: Week 24 ]
    Proportion of subjects with ∆mRSS≥5
14. Quality of life [ Time Frame: Week 52 ]
    Assessed by the health assessment questionnaire disability index
15. Quality of life [ Time Frame: Week 24 ]
    Assessed by the health assessment questionnaire disability index
16. Safety and Tolerability [ Time Frame: Week 52 ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
17. Safety and Tolerability [ Time Frame: Week 24 ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Fulfill EULAR/ACR classification criteria (2013) for systemic sclerosis (SSc).
• Subjects must have mRSS≥10 at screening stage
• Subjects must have signs of fibrosis in their chest CT at screening stage
• If a subject has received treatments before, it should be stable at least 3 months until screening and with no significant efficacy (ΔmRSS≤-2)

Exclusion Criteria:

• Subjects with other connective tissue diseases overlapping with SSc
• Subjects with skin atrophy as the main cutaneous manifestation
• Subjects with active digital ulcers or gangrene
• Active severe SSc-driven renal disease or heart dysfunction at screening
• Subjects with significant hematologic abnormalities
• Abnormal liver function test at screening (ALT, AST or total bilirubin over 2 fold of upper normal level
• Clinically significant active infection including ongoing and chronic infections
• History of human immunodeficiency virus (HIV)
• Confirmed Positive tests for hepatitis B or positive test for hepatitis C
• Active tuberculosis
• Live or attenuated vaccine within 4 weeks prior to screening
• Subjects with significant hematologic abnormalities

Contacts and Locations

Locations

China, Shanghai

RenJi Hospital

Shanghai, Shanghai, China, 200001

Sponsors and Collaborators

RenJi Hospital

More Information

• Responsible Party: RenJi Hospital
• ClinicalTrials.gov Identifier: NCT03068234
• Other Study ID Numbers: [2017]17
• First Posted: March 1, 2017
• Last Update Posted: March 1, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Scleroderma, Systemic; Scleroderma, Diffuse; Pirfenidone; Sclerosis; Pathologic Processes; Connective Tissue Diseases; Skin Diseases; 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