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Efficacy and Safety of Pirfenidone in CTD-ILD

Primary Purpose

Pirfenidone, Connective Tissue Diseases, Interstitial Lung Disease

Status
Recruiting
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Pirfenidone
glucocorticoid and immunosuppressant
Sponsored by
Qilu Hospital of Shandong University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pirfenidone focused on measuring pirfenidone, interstitial lung disease, connective tissue disease, rheumatoid arthritis, systemic sclerosis, inflammatory myopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  1. Age ≥18 years;
  2. Meet several CTD diagnostic criteria (RA, IIM, SSc) and UCTD/IPAF classification criteria;
  3. HRCT diagnosis confirmed interstitial lung disease (ILD) with corresponding clinical manifestations;
  4. Patients who were able to complete vital capacity (FVC) or carbon monoxide dispersion (DLco) tests (with Hb correction).
  5. Patients with clinical deterioration more than 1 month after diagnosis of ILD history, or poor response or intolerance to Glucocorticoids or immunosuppressants treatment, or poor response or intolerance to other antifibrotic drugs (acetyl hemitrine, nidanib, etc.), or effective use of PFD, and exacerbation of clinical symptoms or ILD indicators more than 3 months after withdrawal of the drug.
  6. Poor response was defined as no improvement in one of the following:

(1) Symptoms of dyspnea such as cough, chest tightness, breathlessness, shortness of breath after activity, or decreased activity endurance;

(2) the worst decrease in oxygen saturation as measured by pulse oxygen saturation (SpO) observed during 6MWD;

(3) There was no improvement in pulmonary ventilation (FVC%) or lung dispersion (DLco%);

(4) HRCT findings: new onset, fibrosis tendency or density of ILD lesions were not decreased;

Clinical deterioration was defined as meeting one of three criteria:

  1. Clinical deterioration or dyspnea within 4 weeks;
  2. New or worsening radiological abnormalities on chest X-ray or high-resolution CT;
  3. Objective deterioration of pulmonary function tests or gas exchange, defined as meeting at least one of the following criteria:

1) Start long-term oxygen therapy or increase oxygen supplementation by at least 1 L/min to maintain resting oxygen saturation of at least 90%;

2) FVC decreased by more than 5% compared with the previously measured value; Or a decrease in DLCO of more than 10% from previous measurements; Or a 20% decrease in 6MWD from previous measurements.

7. If concomitant therapy with immunosuppressants was used, the dose was stable for at least 4 weeks before the baseline period. The types of immunomodulator hydroxychloroquine (HCQ) or immunosuppressive agents are MMF, TAC, JAKi, CTX, LEF, AzA, iguratimod etc.

8. Concomitant glucocorticoids: IIM patients with glucocorticoids dose (calculated as the equivalent dose of prednisone) ≤60mg/d and relatively stable disease; For other CTD patients, the glucocorticoids dose (calculated as prednisone equivalent dose) was ≤40mg/ day for at least 1 month.

Exclusion Criteria:

1. Subjects have systemic vasculitis, other arthritis other than CTD or RA such AS psoriatic arthritis, SPA, AS, SLE and pSS;

2. ILD patients with other obvious causes, such as HIV, GVHD, etc.

3. Patients with obvious abnormal combined organ function;

  1. Liver :AST, ALT, R-GT, bilirubin at 1.5 ULN, or previously diagnosed viral hepatitis;
  2. Kidney: creatinine clearance rate 30ml /min;
  3. Lung: airway obstruction (pre-bronchodilator FEV1/FVC & LT; 0.7), pleural effusion accounted for more than 20% of pleural effusion, severe pulmonary infection or other clinically significant pulmonary abnormalities;
  4. Cardiovascular: myocardial infarction within 6 months;
  5. gastrointestinal tract: active peptic ulcer or bleeding;
  6. Blood system: severe anemia, leukopenia, thrombocytopenia;
  7. Nervous system: patients with mental disorders; Cerebral thrombotic events (stroke and transient ischemic attack) within the last 1 year;

4. Tuberculosis, cancer, hereditary diseases and other diseases with poor prognosis;

5. Effective contraception cannot be guaranteed during pregnancy, lactation or childbearing age;

6. Evidence of alcohol or drug abuse, according to the researchers;

7. Allergic to glucocorticoids, immunosuppressants and PFD;

8. Unable to complete regular follow-up and post-treatment pulmonary function tests;

9. PFD users not included in the efficacy analysis but included in the safety analysis: those who had used PFD for less than 3 months 6 months before the primary endpoint; The DURATION OF USE WAS LESS THAN 3 MONTHS BEFORE THE 24TH MONTH OF THE STUDY AND THE TOTAL DURATION OF USE was less THAN 6 months.

Sites / Locations

  • Qilu HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

pirfenidone group

No-pirfenidone group

Arm Description

CTD-ILD patients treated with pirfenidone、glucocorticoid and immunosuppressant.

CTD-ILD patients treated with glucocorticoid and immunosuppressant,without pirfebidone

Outcomes

Primary Outcome Measures

Change in FVC%
change in percentage of forced vital capacity (FVC) from 6 months to baseline

Secondary Outcome Measures

Change in FVC %
change from baseline in percentage of forced vital capacity (FVC)
change in FEV1%、DLco%、TLC%
change from baseline in carbon monoxide diffusing capacity (DLco)、FEV1、TLC
Proportion of patients and time with a decrease in DLco%
Percentage of patients and time with DLco% decreased>15% compared to baseline
Proportion of patients and time with a decrease in FVC%
Percentage of patients and time with FVC% decreased>10% compared to baseline
Progression-free survival
survival with a predicated absolute FVC% decrease of no more than 10% from baseline,and a predicated absolute DLco% decrease of no more than 15% from baseline
change in absolute value of FVC and DLco
absolute value change of FVC(ml) and DLco(ml) at each time point and annual decline rate compared with baseline
changes from baseline in 6 minutes walking distance
changes from baseline in 6 minutes walking distance
change in pulse oxygen saturation
the worst oxygen saturation as measured by pulse oxygen saturation(SpO2) was observed during 6 minutes walking distance
Worsening respiratory symptoms
Proportion of patients with worsening respiratory symptoms at each time point compared with baseline
Advances in imaging
The proportion of patients with disease progression on imaging at each time point compared with baseline
Imaging changes
changes from baseline in high-resolution computed tomography (HRCT)
Borg dyspnea Index score
cChange of Borg dyspnea index score at each time point compared with baseline
clinical deteriorration
The time and incidence of the first clinical deterioration ,Number of clinical exacerbations,Time between the all-cause deaths
Changes from baseline in C-reactive protein (CRP),Erythrocyte Sedimentation Rate(ESR),Inflammatory factors and indicators.
Changes from baseline in C-reactive protein (CRP),Erythrocyte Sedimentation Rate(ESR),Inflammatory factors and indicators.
Changes from baseline in primary disease activity
Changes from baseline in primary disease activity
Adverse events , timing,type,extent,frequency,and outcome of SAE
Adverse events , timing,type,extent,frequency,and outcome of SAE
FVC% area under the curve
forced vital capacity (FVC)% area under the curve
Predicators of pirfenidone response in each disease subgroup
Predicators of pirfenidone response in each disease subgroup

Full Information

First Posted
August 16, 2022
Last Updated
November 27, 2022
Sponsor
Qilu Hospital of Shandong University
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1. Study Identification

Unique Protocol Identification Number
NCT05505409
Brief Title
Efficacy and Safety of Pirfenidone in CTD-ILD
Official Title
Efficacy, Safety, Immune Function of Pirfenidone in the Treatment of Connetive Tissue Disease -Related Interstitial Lung Disease(CTD-LID)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 22, 2022 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Qilu Hospital of Shandong University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A single-center randomized controlled study will be used to observe the efficacy and safety of pirfenidone on CTD-ILD patients for 24 months. The main research endpoints is the lung function (FVC) at 6 months. The clinical dyspnea score, 6-minute walking distance, index of lung function and imaging indicators are evaluated, as well as primary disease activity and adverse reactions of therapy with glucocorticoid and immunosuppressants up to 24 months.
Detailed Description
A total of 120 Chinese patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), including inflammatory myopathy (IIM), rheumatoid arthritis (RA), systemic sclerosis (SSc), and other connective tissue diseases, will be enrolled to use Pirfenidone or not in this study according to 2:1 random entry. Glucocorticoid and immunosuppressants worked as background treatment. The main research endpoint is the lung function (FVC) at 6 months. The clinical dyspnea score, 6-minute walking distance, lung function and imaging indicators, primary disease activity index are evaluated regularly until 24 months. The relationship of pirfenidone concentration, clinical effect and safety, immune function will be analyzed also.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pirfenidone, Connective Tissue Diseases, Interstitial Lung Disease
Keywords
pirfenidone, interstitial lung disease, connective tissue disease, rheumatoid arthritis, systemic sclerosis, inflammatory myopathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
pirfenidone group
Arm Type
Experimental
Arm Description
CTD-ILD patients treated with pirfenidone、glucocorticoid and immunosuppressant.
Arm Title
No-pirfenidone group
Arm Type
Active Comparator
Arm Description
CTD-ILD patients treated with glucocorticoid and immunosuppressant,without pirfebidone
Intervention Type
Drug
Intervention Name(s)
Pirfenidone
Other Intervention Name(s)
glucocorticoid and immunosuppressant
Intervention Description
Drug:pirfenidone CTD-ILD patients treated with pirfenidone up to the maximum tolerable dose Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease
Intervention Type
Drug
Intervention Name(s)
glucocorticoid and immunosuppressant
Intervention Description
Drug: glucocorticoid and immunosuppressant CTD-ILD patients treated with glucocorticoid and immunosuppressant according to the condition of the disease
Primary Outcome Measure Information:
Title
Change in FVC%
Description
change in percentage of forced vital capacity (FVC) from 6 months to baseline
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change in FVC %
Description
change from baseline in percentage of forced vital capacity (FVC)
Time Frame
3months 12 months 24 months
Title
change in FEV1%、DLco%、TLC%
Description
change from baseline in carbon monoxide diffusing capacity (DLco)、FEV1、TLC
Time Frame
3months 6months 12months 24months
Title
Proportion of patients and time with a decrease in DLco%
Description
Percentage of patients and time with DLco% decreased>15% compared to baseline
Time Frame
3months 6months 12months 24months
Title
Proportion of patients and time with a decrease in FVC%
Description
Percentage of patients and time with FVC% decreased>10% compared to baseline
Time Frame
3months 6months 12months 24months
Title
Progression-free survival
Description
survival with a predicated absolute FVC% decrease of no more than 10% from baseline,and a predicated absolute DLco% decrease of no more than 15% from baseline
Time Frame
up to 24months
Title
change in absolute value of FVC and DLco
Description
absolute value change of FVC(ml) and DLco(ml) at each time point and annual decline rate compared with baseline
Time Frame
3months 6months 12months 24months
Title
changes from baseline in 6 minutes walking distance
Description
changes from baseline in 6 minutes walking distance
Time Frame
3months 6months 12months 24months
Title
change in pulse oxygen saturation
Description
the worst oxygen saturation as measured by pulse oxygen saturation(SpO2) was observed during 6 minutes walking distance
Time Frame
up to 24months
Title
Worsening respiratory symptoms
Description
Proportion of patients with worsening respiratory symptoms at each time point compared with baseline
Time Frame
3 months 6months 12months 24months
Title
Advances in imaging
Description
The proportion of patients with disease progression on imaging at each time point compared with baseline
Time Frame
3 months 6months 12months 24months
Title
Imaging changes
Description
changes from baseline in high-resolution computed tomography (HRCT)
Time Frame
6months 12months 24months
Title
Borg dyspnea Index score
Description
cChange of Borg dyspnea index score at each time point compared with baseline
Time Frame
3 months 6months 12months 24months
Title
clinical deteriorration
Description
The time and incidence of the first clinical deterioration ,Number of clinical exacerbations,Time between the all-cause deaths
Time Frame
up to 24months
Title
Changes from baseline in C-reactive protein (CRP),Erythrocyte Sedimentation Rate(ESR),Inflammatory factors and indicators.
Description
Changes from baseline in C-reactive protein (CRP),Erythrocyte Sedimentation Rate(ESR),Inflammatory factors and indicators.
Time Frame
3 months 6months 12months 24months
Title
Changes from baseline in primary disease activity
Description
Changes from baseline in primary disease activity
Time Frame
up to 24months
Title
Adverse events , timing,type,extent,frequency,and outcome of SAE
Description
Adverse events , timing,type,extent,frequency,and outcome of SAE
Time Frame
up to 24months
Title
FVC% area under the curve
Description
forced vital capacity (FVC)% area under the curve
Time Frame
3months 6months 12months 24months
Title
Predicators of pirfenidone response in each disease subgroup
Description
Predicators of pirfenidone response in each disease subgroup
Time Frame
3months 6months 12months 24months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Age ≥18 years; Meet several CTD diagnostic criteria (RA, IIM, SSc) and UCTD/IPAF classification criteria; HRCT diagnosis confirmed interstitial lung disease (ILD) with corresponding clinical manifestations; Patients who were able to complete vital capacity (FVC) or carbon monoxide dispersion (DLco) tests (with Hb correction). Patients with clinical deterioration more than 1 month after diagnosis of ILD history, or poor response or intolerance to Glucocorticoids or immunosuppressants treatment, or poor response or intolerance to other antifibrotic drugs (acetyl hemitrine, nidanib, etc.), or effective use of PFD, and exacerbation of clinical symptoms or ILD indicators more than 3 months after withdrawal of the drug. Poor response was defined as no improvement in one of the following: (1) Symptoms of dyspnea such as cough, chest tightness, breathlessness, shortness of breath after activity, or decreased activity endurance; (2) the worst decrease in oxygen saturation as measured by pulse oxygen saturation (SpO2) observed during 6MWD; (3) There was no improvement in pulmonary ventilation (FVC%) or lung dispersion (DLco%); (4) HRCT findings: new onset, fibrosis tendency or density of ILD lesions were not decreased; Clinical deterioration was defined as meeting one of three criteria: Clinical deterioration or dyspnea within 4 weeks; New or worsening radiological abnormalities on chest X-ray or high-resolution CT; Objective deterioration of pulmonary function tests or gas exchange, defined as meeting at least one of the following criteria: 1) Start long-term oxygen therapy or increase oxygen supplementation by at least 1 L/min to maintain resting oxygen saturation of at least 90%; 2) FVC decreased by more than 5% compared with the previously measured value; Or a decrease in DLCO of more than 10% from previous measurements; Or a 20% decrease in 6MWD from previous measurements. 7. If concomitant therapy with immunosuppressants was used, the dose was stable for at least 4 weeks before the baseline period. The types of immunomodulator hydroxychloroquine (HCQ) or immunosuppressive agents are MMF, TAC, JAKi, CTX, LEF, AzA, iguratimod etc. 8. Concomitant glucocorticoids: IIM patients with glucocorticoids dose (calculated as the equivalent dose of prednisone) ≤60mg/d and relatively stable disease; For other CTD patients, the glucocorticoids dose (calculated as prednisone equivalent dose) was ≤40mg/ day for at least 1 month. Exclusion Criteria: 1. Subjects have systemic vasculitis, other arthritis other than CTD or RA such AS psoriatic arthritis, SPA, AS, SLE and pSS; 2. ILD patients with other obvious causes, such as HIV, GVHD, etc. 3. Patients with obvious abnormal combined organ function; Liver :AST, ALT, R-GT, bilirubin at 1.5 ULN, or previously diagnosed viral hepatitis; Kidney: creatinine clearance rate 30ml /min; Lung: airway obstruction (pre-bronchodilator FEV1/FVC & LT; 0.7), pleural effusion accounted for more than 20% of pleural effusion, severe pulmonary infection or other clinically significant pulmonary abnormalities; Cardiovascular: myocardial infarction within 6 months; gastrointestinal tract: active peptic ulcer or bleeding; Blood system: severe anemia, leukopenia, thrombocytopenia; Nervous system: patients with mental disorders; Cerebral thrombotic events (stroke and transient ischemic attack) within the last 1 year; 4. Tuberculosis, cancer, hereditary diseases and other diseases with poor prognosis; 5. Effective contraception cannot be guaranteed during pregnancy, lactation or childbearing age; 6. Evidence of alcohol or drug abuse, according to the researchers; 7. Allergic to glucocorticoids, immunosuppressants and PFD; 8. Unable to complete regular follow-up and post-treatment pulmonary function tests; 9. PFD users not included in the efficacy analysis but included in the safety analysis: those who had used PFD for less than 3 months 6 months before the primary endpoint; The duration of use was less than 3 months before the 24th month of the syudy and the total duration of use was less than 6 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qiang Shu, Dr
Phone
0086-0531-82169654
Email
shuqiang@sdu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
keke xie
Phone
0086-0531-82169654
Email
695052518@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
xiaoyun yang, Dr
Organizational Affiliation
Study Principal Investigator Qilu HOspital of Shandong Uniwersity
Official's Role
Principal Investigator
Facility Information:
Facility Name
Qilu Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250012
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
xiaoyun yang
Phone
+8653182169035
Email
qlyykyc@163.com

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of Pirfenidone in CTD-ILD

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