Phase ll Study of Pirfenidone in Patients With RAILD

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 17-002207
    NCT ID: NCT02808871
    Sponsor Protocol Number: TRAIL1

About this study

The purpose of this study is to to assess the safety and tolerability of pirfenidone 2403 mg/day for the treatment of RA-associated interstitial lung disease.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Age 18 through 85 years, inclusive, at Screening.
  • Probable or definite diagnosis of RA according to revised 2010 ACR/EULAR criteria, without evidence or suspicion of an alternative diagnosis that may contribute to their interstitial lung disease.
  • Diagnosis of ILD:
    • supported by clinically indicated HRCT, and when available, surgical lung biopsy (SLB), prior to Screening; and
    • presence of fibrotic abnormality affecting more than 10% of the lung parenchyma, with or without traction bronchiectasis or honeycombing, on Screening and confirmed by adjudicated HRCT prior to Baseline.
  • No features supporting an alternative diagnosis on transbronchial biopsy, or SLB, if performed prior to Screening.
  • Attainment of the following centralized spirometry criteria (based on local spirometry on standardized equipment and centralized quality controlled):
    • percent predicted FVC ≥ 40% at Screening;
    • change in pre-bronchodilator FVC (measured in liters) between Screening (Visit 1) and Baseline (Visit 2) must be a <10% relative difference, calculated as:
    • 100% * [absolute value (Screening FVC – Baseline FVC) / Screening FVC ];
    • percent predicted DLCO ≥30 % at Screening.
  • Able to understand and sign a written informed consent form.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, during the 52 week treatment period and for at least 118 days after the last dose of study drug.
    • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
    • Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, established and proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
    • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
    • With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 118 days after the last dose of study drug.
    • Men must refrain from donating sperm during this same period.

Exclusion Criteria:

  • Not a suitable candidate for enrollment or unlikely to comply with the requirements of this study, in the opinion of the investigator.
  • Cigarette smoking within 3 months of Screening or unwilling to avoid tobacco products throughout the study.
  • History of clinically significant environmental exposure known to cause pulmonary fibrosis (PF), including but not limited to drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds.
  • Concurrent presence of the following conditions:
    • Other interstitial lung disease, related to but not limited to radiation, drug toxicity, sarcoidosis, hypersensitivity pneumonitis, or bronchiolitis obliterans organizing pneumonia;
    • Medical history including Human Immunodeficiency Virus (HIV);
    • Medical history of viral hepatitis (positive Hep A antibody in the absence of elevated liver enzymes is not an exclusion).
  • Concurrent presence of other pleuropulmonary manifestations of RA, including but not limited to rheumatoid nodular disease of the lung, pleuritis/pleural thickening, and obliterative bronchiolitis.
  • Post-bronchodilator FEV1/FVC < 0.7 at Screening.
  • Presence of pleural effusion occupying more than 20% of the hemithorax on Screening HRCT.
  • Clinical diagnosis of a second connective tissue disease or overlap syndrome (including but not limited to scleroderma, Sjogren’s, polymyositis/dermatomyositis, systemic lupus erythematosus but excluding Raynaud’s phenomena).
  • Coexistent clinically significant COPD/emphysema or asthma in the opinion of the site principal investigator.
  • Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis, urinary tract infection, or cellulitis. The infection should be resolved per PI assessment prior to enrollment. Any use of antibiotics must be completed 2 weeks prior to the screening visit. Note that prophylactic antibiotics are not contraindicated or exclusionary.
  • Any history of malignancy diagnosed within 5 years of screening, other than basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or low grade cervical carcinoma in situ.
  • History of LFT abnormalities as outlined below, or imaging, laboratory or other clinical information suggesting liver dysfunction, advanced liver disease or cirrhosis. Evidence of hepatic impairment that in the opinion of the investigator could interfere with drug metabolism or increase the risk of the known hepatotoxicity of study drug.
  • Any of the following liver function abnormalities:
    • Total bilirubin above the upper limit of normal (ULN), excluding patients with Gilbert’s syndrome;
    • Aspartate or alanine aminotransferase (AST/SGOT or AST/SGPT) > 3 X ULN;
    • Alkaline phosphatase > 2.5 X ULN.
  • History of end-stage renal disease requiring dialysis.
  • History of unstable or deteriorating cardiac disease, or unstable cardiac arrhythmia or arrhythmia requiring modification of drug therapy, myocardial infarction within the previous year, heart failure requiring hospitalization. Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone.
  • History of alcohol or substance abuse in the past 2 years, at the time of Screening.
  • Family or personal history of long QT syndrome.
  • Any of the following test criteria above specified limits:
    • Estimated glomerular filtration rate <57 mL/min/1.73m2;
    • ECG with a QTc interval >500 msec at Screening.
  • Prior use of pirfenidone or known hypersensitivity to any of the components of study treatment.
  • Use of any of the following therapies within 28 days before Screening and during participation in the study:
    • Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site;
    • Potent inhibitors of CYP1A2(e.g., fluvoxamine, enoxacin);
    • Potent inducers of CYP1A2;
    • Sildenafil (daily use).
      • Note: intermittent use for erectile dysfunction is allowed.
  • Introduction and/or modification of dose of corticosteroids or any cytotoxic, immunosuppressive, or cytokine modulating or receptor antagonist agent for the management of pulmonary manifestations of RA, within 3 months of screening, is an exclusion criterion for enrollment, with the exception of dose modification of systemic corticosteroids that are maintained at or below 20 mg prednisone daily or the equivalent.
  • However, introduction and/or modification of dose of corticosteroids or any cytotoxic, immunosuppressive, or cytokine modulating or receptor antagonist agent for the management of extrapulmonary manifestations of RA is not an exclusion criterion.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Andrew Limper, M.D.

Open for enrollment

Contact information:

Hope Marlow

(507)284-2122

Marlow.Hope@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20359112

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