A Phase I Study to Evaluate the Safety and Preliminary Efficacy of Atezolizumab in Idiopathic Pulmonary Fibrosis
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- Cedars-Sinai Medical Center
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
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).
Detailed 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.
Investigators
Tanzira Zaman
Assistant Professor of Medicine
Cedars-Sinai Medical Center
Eligibility Criteria
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
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
Arms & Interventions
Atezolizumab
Atezolizumab 1200 mg IV every 3 weeks for 24 weeks
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events
Time Frame: 24 weeks
Number of participants with treatment-related adverse events as defined by NCI CTCAE v4.03
Secondary Outcomes
- St. George's Respiratory Questionnaire(24 weeks)
- University of California San Diego (UCSD) Shortness of Breath Questionnaire(24 weeks)
- Radiologic extent of fibrosis(24 weeks)
- Forced vital capacity(24 weeks)
- Six minute walk distance(24 weeks)