Pirfenidone as Treatment of Skin Fibrosis in Systemic Sclerosis

A Randomized, Double-blinded, Placebo Controlled Study to Evaluate Clinical Efficacy and Safety of Pirfenidone for Skin Fibrosis in Systemic Sclerosis

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.

Study Overview

• Status: Unknown
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Drug: Pirfenidone; Drug: Steroids; Drug: Placebo oral capsule

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 Type: Interventional
• Enrollment (Anticipated): 72
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Renji Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Steroids; Low dose of glucocorticoids, a basic treatment for patients with systemic sclerosis; Drug: Placebo oral capsule; Placebo for pirfenidone capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rodnan Skin Score (mRSS）	A semi-quantitative score for skin fibrosis of every subjects	Week 52

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2017
• Primary Completion (Anticipated): April 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 1, 2017
• Last Update Submitted That Met QC Criteria: February 24, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; 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: [2017]17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No