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Pilot Study of Pirfenidone in Pulmonary Fibrosis With Anti-myeloperoxydase Antibodies (PIRFENIVAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03385668
Recruitment Status : Completed
First Posted : December 28, 2017
Last Update Posted : May 3, 2021
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Study Description
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Brief Summary:
The purpose of this study is to determine wether pirfenidone is safe and effective in the treatment of pulmonary fibrosis with anti-myeloperoxydase (MPO) antibodies or pulmonary fibrosis with anti-MPO associated vasculitis.

Condition or disease Intervention/treatment Phase
Pulmonary Fibrosis Drug: Pirfenidone Phase 2

Detailed Description:

Pulmonary fibrosis can be associated with Anti-Neutrophil Cytoplasmic Antibody (ANCA) directed against MPO or with anti-MPO associated vasculitis, leading to increased disability and poor prognosis. The pathophysiology of this association remains unclear. Conventional therapies used for the treatment of vasculitis manifestations are often disappointing for the treatment of pulmonary fibrosis. The main cause of death in patients with anti-MPO ANCA associated vasculitis and associated pulmonary fibrosis is the progression of pulmonary fibrosis. No treatment has demonstrated efficacy to stabilize or improve pulmonary fibrosis associated with anti-MPO associated vasculitis.

Previous studies showed that Pirfenidone improves survival and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF) and that Pirfenidone treatment is safe and well tolerated in IPF. Patients with anti-MPO associated vasculitis (or anti-MPO antibodies without vasculitis) and associated pulmonary fibrosis might benefit from the use of Pirfenidone. However, the efficacy and safety of pirfenidone in patients with anti-MPO associated vasculitis and associated pulmonary fibrosis has not been evaluated. This study was designed to assess the efficacy and safety of pirfenidone in patients with pulmonary fibrosis and anti-MPO ANCA associated vasculitis or anti-MPO antibodies without vasculitis.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Efficacy and Safety of Pirfenidone in Patients With Pulmonary Fibrosis With Anti-myeloperoxydase (MPO) Antibodies or With Anti-MPO Associated Vasculitis."
Actual Study Start Date : January 31, 2018
Actual Primary Completion Date : July 24, 2020
Actual Study Completion Date : July 24, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Pirfenidone

Arms and Interventions
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Arm Intervention/treatment
Experimental: Pirfenidone
All patients will receive Pirfenidone
 Drug: Pirfenidone
Pirfenidone at a dose of 2403 mg/day for 50 weeks, after a 2 weeks period of titration (801 mg/day for one week then 1602 mg/day for one week).


Outcome Measures
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Primary Outcome Measures :
  1. Treatment efficacy measured by the absolute change in percent predicted forced vital capacity (%FVC) [ Time Frame: 52 weeks ]

    Treatment efficacy at Week 52 measured by the absolute change from baseline to Week 52 in percent predicted forced vital capacity (%FVC) :

    • Patients with progressive disease will be defined as absolute decline of 10% or more in %FVC. Missing values or death will be also considered as progressive.
    • Patients with non-progressive disease will be defined as improvement or no decline in %FVC or a decline of %FVC<10%.


Secondary Outcome Measures :
  1. Adverse Events (AE) [ Time Frame: 56 weeks corresponding to 28 days after the last dose of study drug ]

    Safety parameters reported in the period from baseline to 28 days after the last dose of the study drug:

    • Treatment-emergent AEs
    • Treatment-emergent Serious Adverse Events (SAE)
    • Treatment emergent Adverse Event of Special Interest (AESI)
    • Treatment-emergent treatment-related AEs
    • Treatment-emergent treatment-related SAEs
    • Treatment emergent related AESIs
    • AEs leading to early discontinuation of study treatment
    • Treatment-emergent deaths
    • Cause of death
    • Treatment-emergent changes in clinical laboratory findings
    • Vital signs

  2. Treatment efficacy measured by the absolute change in percent predicted forced vital capacity (%FVC) [ Time Frame: 24 weeks ]

    Treatment efficacy at Week 24 measured by the absolute change from baseline to Week 24 in percent predicted forced vital capacity (%FVC) :

    • Patients with progressive disease will be defined as absolute decline of 10% or more in %FVC. Missing values or death will be also considered as progressive.
    • Patients with non-progressive disease will be defined as improvement or no decline in %FVC or a decline of %FVC<10%.

  3. Relative change in in percent predicted forced vital capacity [ Time Frame: 52 weeks ]
    Relative change from baseline to Week 52 in percent predicted forced vital capacity (%FVC)

  4. Absolute change in in percent predicted forced vital capacity [ Time Frame: 52 weeks ]
    Relative and absolute change from baseline to Week 52 in percent predicted forced vital capacity (%FVC)

  5. Relative change in in percent predicted forced vital capacity [ Time Frame: 24 weeks ]
    Relative and absolute change from baseline to Week 24 in percent predicted forced vital capacity (%FVC)

  6. Absolute change in in percent predicted forced vital capacity [ Time Frame: 24 weeks ]
    Relative and absolute change from baseline to Week 24 in percent predicted forced vital capacity (%FVC)

  7. Six minute walk test (6MWT) distance [ Time Frame: 52 weeks ]
    Change from Baseline to Week 52 in the six minute walk test (6MWT) distance

  8. Six minute walk test (6MWT) distance [ Time Frame: 24 weeks ]
    Change from Baseline to Week 24 in the six minute walk test (6MWT) distance

  9. Carbon Monoxide Diffusing Capacity (%DLCO) [ Time Frame: 52 weeks ]
    Change from Baseline to Week 52 in the percent predicted Carbon Monoxide Diffusing Capacity (%DLCO)

  10. Carbon Monoxide Diffusing Capacity (%DLCO) [ Time Frame: 24 weeks ]
    Change from Baseline to Week 24 in the percent predicted Carbon Monoxide Diffusing Capacity (%DLCO)

  11. Progression-free survival [ Time Frame: 52 weeks ]
    Progression-free survival defined as the time to the first occurrence of any one of the following: a confirmed decrease of 10 percentage points or more in %FVC, a confirmed decrease of 15 percentage points or more in %DLCO, or death.

  12. Dyspnea [ Time Frame: 52 weeks ]
    Change from Baseline to Week 52 in dyspnea as measured by the New York Heart Association classification, the modified Borg scale and by the Saint-George's Respiratory Questionnaire (SGRQ).

  13. Chest CT-scan [ Time Frame: 52 weeks ]
    Change in Chest-CT scan abnormalities at Week 52 (evaluated after a centralized blinded review of the chest CT-scans).

  14. Quality of Life assessed by the Health Assessment Questionnaire (HAQ) [ Time Frame: 52 weeks ]
  15. Quality of Life assessed by the Short Form-36 (SF-36) [ Time Frame: 52 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years
  • Presence of anti-MPO antibody (ELISA) at inclusion or during pulmonary fibrosis follow-up and/or diagnosis of anti-MPO associated vasculitis according to the 2012 Revised International Chapel Hill Consensus Conference definitions
  • Definite or possible Usual Interstitial Pneumonia or Non Specific Interstitial Pneumonia based on high-resolution computed tomography
  • Presence of pulmonary fibrosis, defined as a range of 50 to 90% of the %FVC and a range of 30 to 90% of the %DLCO
  • Pulmonary fibrosis refractory (according to the investigator's judgment) to a conventional regimen used for anti-MPO associated vasculitis when a treatment against vasculitis has been used
  • Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information) and comply with the study protocol procedures (including required study visits)
  • Have affiliation with a mode of social security (profit our being entitled).

Exclusion Criteria:

  • Other type of systemic vasculitis;
  • Active vasculitis defined by Birmingham Vasculitis Activity Score >3 (BVAS) ;
  • Contraindication to Pirfenidone;
  • Unable to perform pulmonary function test (PFT);
  • Pregnancy or lactation. Women of childbearing capacity are required to have a negative serum pregnancy test before treatment and must agree to maintain highly effective contraception by practicing abstinence or by using an effective method of birth control from the date of consent through the end of the study : implants of levonorgestrel; injectable progesterone; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progesterone only); double barrier method (condom, cervical cap or diaphragm with spermicidal agent); transdermal contraceptive patch; male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subject;
  • Any of the following liver function test criteria above specified limits: total bilirubin above 1,5 times the upper limit of normal (ULN), excluding patients with Gilbert's syndrome; aspartate (AST)/Glutamate Oxaloacétique Transaminase (SGOT) or alanine aminotransferase (ALT)/Glutamate Pyruvate Transaminase (SGPT), (AST/SGOT or ALT/SGPT) >3 × ULN; alkaline phosphatase >2.5 × ULN;
  • Creatinine clearance (CrCl<30) mL/min, calculated using the Cockcroft-Gault formula at screening
  • Current treatment with Nintedanib or past treatment with Nintedanib in the last 12 months;
  • Current treatment with Fluvoxamine or past treatment with Fluvoxamine in the last 28 days before screening
  • Prior use of Pirfenidone or known hypersensitivity to any of the components of study treatment;
  • Expected to receive a lung transplant within 1 year from randomization or, on a lung transplant waiting list at randomization;
  • Associated connective tissue disease (such as systemic sclerosis).;
  • Electrocardiogram (ECG), with a heart-rate-corrected QT interval (corrected using Fridericia's formula, QTcF) ≥ 500 ms at Screening, or a family or personal history of long QT syndrome;
  • Treatment with Cyclophosphamide in the last 3 months;
  • Current smoking or past smoking in the last 3 months.
Contacts and Locations
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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): NCT03385668


Locations
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France
Cochin Hospital
Paris, France, 75014
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Roche Pharma AG
Investigators
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Principal Investigator: Jonathan London, MD Cochin Hospital
More Information
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Publications:

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03385668    
Other Study ID Numbers: P161001J
2017-002782-22 ( EudraCT Number )
First Posted: December 28, 2017    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Pulmonary fibrosis
Antibodies, Antineutrophil Cytoplasmic
Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
 Pirfenidone
Microscopic Polyangiitis
Interstitial lung disease
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract 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