A study of efficacy and safety of various treatments in participants with idiopathic pulmonary fibrosis (IPF)

Prior treatment

• Active drug or alcohol abuse (as defined by the investigator) within 3 months prior to screening.
• Use of any inhaled substance, including but not limited to tobacco or marijuana products and/ or the use of any electronic cigarette or vaping device, within 12 weeks prior to screening (note that respiratory inhalers or nebulizers for delivery of prescribed medication for pulmonary disease are allowed).
• Currently receiving high-dose corticosteroid, cytotoxic therapy (e.g. chlorambucil, azathioprine, cyclophosphamide, methotrexate), vasodilator therapy for pulmonary hypertension (e.g. bosentan), unapproved (e.g. IFN-γ, penicillamine, cyclosporine, mycophenolate, N-acetylcysteine [may vary by country]) and/or investigational therapy or device for IPF or administration of such therapeutics within 5 half-lives of the IP prior to initial screening in this study. A current dose of ≤5 mg/day of prednisone or its equivalent is acceptable if the dose is expected to remain stable during the study. (Note: N-Acetylcysteine used to treat cough is permissible).
• Blood donation of 1 unit (approximately 473mL) or more within 1 month prior to screening.
• Elective surgery planned to take place during this trial (excluding diagnostic procedures such as colonoscopy, etc.)
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using appropriate methods of contraception for 3 months prior to screening, during dosing, and for a period after stopping of investigational medication (any treatment specific contraception requirements and changes to duration or if WOCBP cannot be enrolled at all are outlined in Section 17).
• Serious local infection (e.g. cellulitis, abscess) or systemic infection that required hospitalization or was clinically significant in the opinion of the investigator, within 3 months prior to screening
• Fever (body temperature >38 degrees Celsius) or symptomatic viral or bacterial infection within 2 weeks prior to screening or randomization • A known or suspected symptomatic Covid diagnosis within 3 months of screening visit or prior to randomization
• Current hepatitis C infection (defined as positive HCV antibody and detectable HCV ribonucleic acid [RNA]). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study. Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] or positive anti-HBc with a negative anti-HBs). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study.

Other illness

• Pulmonary hypertension requiring pharmacologic treatment
• History of major organ, hematopoietic stem cell or bone marrow transplant
• Clinical diagnosis of any connective tissue disease (including but not limited to scleroderma, polymyositis/ dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis) or a diagnosis of interstitial pneumonia with autoimmune features as determined by the investigator applying the recent ERS/ ATS research statement. Note: serological testing is not needed if not clinically indicated.
• Other known causes of interstitial lung disease (e.g. domestic or occupational environmental exposures, drug toxicity) or another identifiable interstitial lung disease
• History of hypersensitivity to the study drug or to drugs of similar chemical classes in the cohort the participant is to be randomized
• History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) (enzyme-linked immunosorbent assay [ELISA] and western blot) test result
• History of malignancy of any organ system (other than completely excised, localized carcinoma of the skin such as basal cell or squamous cell carcinoma or in situ cervical cancer), treated or untreated, within the past 5 years of screening, regardless of whether there is evidence of local recurrence or metastases
• Significant cardiac disease (e.g. New York Heart Association Class 3 or 4; myocardial infarction within the past 6 months of screening; unstable angina; coronary angioplasty or coronary artery bypass graft within the past 6 months of screening; uncontrolled atrial or ventricular cardiac arrhythmias).

Lab values

• Any surgical, medical (e.g. uncontrolled hypertension, diabetes), psychiatric or additional physical condition that the investigator feels may jeopardize the participant in case of participation in this study. The investigator should make this determination in consideration of the patient’s medical history and/or clinical or laboratory evidence of any of the following: • Moderate or severe hepatic failure (Child-Pugh classification stage B or C) • Significant renal impairment with an estimated glomerular filtration rate (eGFR) < 30 mL/min as calculated by the CKD-EPI formula
• Any one of the following screening values of complete blood count laboratory values: • Hemoglobin levels < 10.0 g/dL • Total leukocyte count < 3,000/μL • Neutrophils <1.5 x 103 /μL • Platelets <100.0 x 103 /μL • Total Bilirubin > 1.5 mg/dL (in the absence of known Gilbert's syndrome) • Aspartate transaminase (AST) or alanine transaminase (ALT) > 2X upper limit of normal
• Male or female planning a pregnancy during the duration of this study. A serum pregnancy test will be performed on all female participants of childbearing potential.

Other

• Unable to perform PFTs, 6MWT or undergo HRCT procedure at time of screening
• Inability to comply with study requirements.
• Other unspecified reason that in the opinion of the investigator in consultation with the sponsor makes the participant unsuitable for enrollment
• Peripheral capillary oxygen saturation (SpO2) <90% at rest (if on supplemental oxygen, must be ≤2 L/min at rest)
• Airway obstruction (i.e., prebronchodilator FEV1/ FVC < 0.7) or evidence of a bronchodilator response at screening as defined by an absolute increase of ≥12% and an increase of ≥ 200ml in FEV1 or FVC, or both, after bronchodilator use, compared with the values before bronchodilator use at screening.
• Emphysema >20% on screening HRCT as assessed visually by central reader.
• Fibrosis <10% on screening HRCT as assessed visually by central reader.
• Clinically diagnosed acute exacerbation of IPF (AE-IPF) or other significant clinical worsening within 3 months of randomization
• Plan to enroll in another interventional trial while in this study
• Pregnant or nursing (lactating) women

• Written informed consent must be obtained before any assessment is performed.
• Male and female participants at least 40 years of age
• IPF diagnosed based on ATS/ERS/JRS/ALAT IPF 2018 modified guideline for diagnosis and management, within 5 years of screening (HRCT and surgical lung biopsy or cryobiopsy (if available) will be read by a central reader)
• FVC ≥45% predicted at screening with no clinically significant deterioration, as determined by investigator between the screening visit and randomization, as determined by the investigator.
• DLCO, corrected for hemoglobin, ≥25% predicted (inclusive) at screening with no clinically significant deterioration, as determined by investigator between the screening visit and randomization, as determined by the investigator.
• Unlikely to die from cause other than IPF within the next 2 years, in the opinion of the investigator
• Unlikely to undergo lung transplantation during this trial in the opinion of the investigator
• If a participant is taking nintedanib or pirfenidone, they must be on a stable regimen for at least 8 weeks prior to randomization
• Able to communicate well with the investigator, to understand and comply with the requirements of the study