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Atezolizumab for Idiopathic Pulmonary Fibrosis

Recruiting
50 - 80 years of age
Both
Phase 1

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Overview

The purpose of this study is to determine the safety and preliminary efficacy of atezolizumab, an immune checkpoint inhibitor approved for the treatment of various cancers, in patients with idiopathic pulmonary fibrosis (IPF).

Description

IPF is a progressive scarring condition of the lung that primarily affects adults aged 60 and above. There is a tremendous need to identify therapies that can stop the progression of fibrosis in IPF. No such drugs exist to date, and preclinical studies suggest that immune checkpoint inhibitors such as atezolizumab may halt the progression of IPF.

Adults between the ages of 50 and 80 years with IPF and meeting further inclusion/exclusion criteria will be eligible for the study. Presently, there are two medications that are considered the standard-of-care for the treatment of IPF. Subjects will be able to continue standard-of-care while taking the study drug.

The primary research procedures are experimental treatment with atezolizumab over 24 weeks administered at a standard dose and route of administration approved for the treatment of cancer. The primary objective of the study is to assess the safety and tolerability of atezolizumab with or without standard of care therapy in subjects with IPF. The secondary objectives of the study are to determine change in forced vital capacity, qualitative radiographic change in extent of fibrosis, and patient-reported outcomes with atezolizumab in subjects with IPF over 28 weeks.

Eligibility

Inclusion Criteria:

  • Males or females ≥50 years of age
  • Confident diagnosis of IPF per 2018 ATS/ERS/JRS/ALAT Clinical Practice Guideline on Diagnosis of IPF1
    • Subjects must have a high-resolution computed tomography (HRCT) completed in the 6 months prior to informed consent
    • Subjects must have HRCT pattern of definite or probable UIP
    • Subjects without HRCT pattern of definite or probable UIP must have surgical lung biopsy showing histopathology consistent with UIP
    • Extent of fibrotic changes must be greater than the extent of emphysema on HRCT
  • Review of all available IPF treatment options with the potential subject prior to

    consent for participation in the study

  • Negative hepatitis B surface antigen (HBsAg) test at screening
  • Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAB test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
  • Negative hepatitis C antibody
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
        Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per
        year during the treatment period and for 5 months after the final dose of atezolizumab.
        Women must refrain from donating eggs during this same period.
        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). The definition of childbearing potential may be adapted for
        alignment with local guidelines or requirements.
        Examples of contraceptive methods with a failure rate of < 1% per year include bilateral
        tubal ligation, male sterilization, 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: agreement to remain abstinent (refrain from heterosexual intercourse) or use a
        condom, and agreement to refrain from donating sperm, as defined below:
        With a female partner of childbearing potential or pregnant female partner, men must remain
        abstinent or use a condom during the treatment period and for 5 months after the final dose
        of atezolizumab to avoid exposing the embryo. Men must refrain from donating sperm during
        this same period.
        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 preventing drug exposure.
        Exclusion Criteria:
          -  FVC <50% of predicted, DLCO < 30% of predicted, FEV1/FVC ratio <0.7
          -  Significant clinical worsening of IPF between screening and baseline visits as defined
             by > 10% decline in FVC or new requirement for supplemental oxygen
          -  Evidence of secondary etiologies of ILD (signs/symptoms of connective tissue disease,
             including ANA titer > 1:80, history of exposures related to hypersensitivity
             pneumonitis, history of drug-related pulmonary toxicity, occupational exposures)
          -  Evidence of comorbid pulmonary pathology including but not limited to asthma,
             tuberculosis, sarcoidosis, chronic infections
          -  Any acute illness or febrile event that has not resolved at least 14 days prior to
             either screening or dosing
          -  Use of tobacco-containing products within the last 3 months and/or unwillingness to
             abstain from use for the duration of the study
          -  Participation in a clinical study involving administration of other investigational
             drugs in the 30 days prior to screening
          -  Any condition that in the opinion of the investigators would confound the ability to
             interpret data from the study
          -  QTc > 470 msec
          -  Any comorbid condition that is likely to result in death within the next year
          -  Inability to obtain reproducible, high-quality pulmonary function tests
          -  Likelihood of lung transplantation in the first 24 weeks of the study
          -  Use of other IPF-directed therapies beside SOC including but not limited to
             endothelium receptor antagonists, interferon gamma-1b, N-acetylcysteine
          -  Initiation of pirfenidone or nintedanib less than 90 days prior to screening
          -  Current therapy or treatment within 60 days prior to screening of any cytotoxic or
             immunosuppressive medications, cytokine modulating therapies, and oral anticoagulants
             within 4 weeks of the screening visit. Note: oral anticoagulants taken for alternative
             diagnoses are acceptable and should not be discontinued for the sole purpose of study
             participation.
          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
          -  Use of an inhaled long-acting bronchodilator within 24 hours of the Screening Visit or
             short-acting bronchodilator within 8 hours of the Screening Visit
          -  History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 6 months of
             the Screening Visit and/or recurrent DVT or recurrent PE
          -  Active or history of recurrent bacterial, viral, fungal, mycobacterial or other
             infections (including, but not limited to, atypical mycobacterial disease and herpes
             zoster), or any major episode of infection requiring hospitalization or treatment with
             intravenous or oral antibiotics within 4 weeks of the Screening Visit and at any time
             during the Screening Phase, up through the first dose of study drug
          -  History of latent or active TB, unless there is medical record documentation of
             successful completion of a standard course of treatment for latent TB
          -  Diagnosis of any clinically significant autoimmune disease, with the exclusion of
             vitiligo and diabetes mellitus.
          -  Pregnancy or lactation
          -  History of leptomeningeal disease
          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently) Patients with indwelling
             catheters (e.g., PleurX) are allowed.
          -  Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12
             mg/dL or corrected serum calcium > ULN)
          -  Significant cardiovascular disease (such as New York Heart Association Class II or
             greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
             months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
          -  Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation
             of study treatment, or anticipation of need for a major surgical procedure during the
             study
          -  History of malignancy, with the exception of malignancies with a negligible risk of
             metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma
             in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal
             carcinoma in situ, or Stage I uterine cancer
          -  Prior allogeneic stem cell or solid organ transplantation
          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding that contraindicates the use of an investigational drug, may affect
             the interpretation of the results, or may render the patient at high risk from
             treatment complications
          -  Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
             treatment, or anticipation of need for such a vaccine during atezolizumab treatment or
             within 5 months after the final dose of atezolizumab
          -  Current treatment with anti-viral therapy for HBV
          -  History of severe allergic anaphylactic reactions to chimeric or humanized antibodies
             or fusion proteins
          -  Known hypersensitivity to Chinese hamster ovary cell products or to any component of
             the atezolizumab formulation
          -  Women of childbearing potential must have a negative serum pregnancy test result
             within 14 days prior to initiation of study treatment.
          -  Patients at increased risk of adverse outcomes given the known safety profile for
             atezolizumab and SOC medications (hepatitis, colitis, endocrinopathies,
             nephritis/renal dysfunction, exfoliative dermatitis)

Study details

Idiopathic Pulmonary Fibrosis

NCT05515627

Cedars-Sinai Medical Center

25 January 2024

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