A Randomized, Double-Blind, Placebo-controlled study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of CSL312 in Subjects with Idiopathic Pulmonary Fibrosis (H-51537)
Study Product: CSL312 (Garadacimab, factor XIIa antagonist monoclonal antibody) for treatment of idiopathic pulmonary fibrosis (IPF).
- Capable of providing written informed consent and willing and able to adhere to all protocol requirements.
- Male or female patients, ≥40 years of age at time of providing written informed consent.
- Documented diagnosis of IPF according to investigator using criteria from 2018 Clinical Practice Guideline of the American Thoracic Society (ATS)/European Respiratory Society (ERS) / Japanese Respiratory Society (JRS) / Latin American Thoracic Association (ALAT) for the diagnosis of IPF at time of screening.
- Forced vital capacity (FVC) ≥ 45% of predicted normal at screening.
- Diffusing capacity of lungs for carbon monoxide (DLCO, corrected for hemoglobin) ≥ 30% of predicted normal at screening.
- Forced expiratory volume in 1 second (FEV1)/FVC ratio ≥ 0.7 at screening.
- Investigator believes that subject (or subject's legally acceptable representative) understands the nature, scope, and possible consequences of the study.
- History of clinically significant cardiovascular disease, including myocardial infarction, unstable ischemic heart disease, congestive heart failure, or angina during the 6 months before Screening.
- Resting pulse < 50 beats per minute, sinoatrial or atrioventricular block, uncontrolled hypertension, or QT interval corrected using the Fridericia formula (QTcF)>450 milliseconds.
- Active bleeding or current clinically significant coagulopathy (eg, international normalized ratio [INR] > 1.5) or clinicallysignificant risk for bleeding (eg, recent intracranial hemorrhage or bleeding peptic ulcer within the 4 weeks before Screening).
- History of venous thrombosis or cerebrovascular event within the 3 months before Screening, or a prothrombotic disorder (eg, antithrombin III, protein C, or protein S deficiency or antiphospholipid syndrome).
- Known or suspected severe infusion-related reaction or hypersensitivity to monoclonal antibody therapy, or hypersensitivity to the investigational product or any excipients of the investigational product.
- Major surgery scheduled to occur during the study or up to 90 days after the last administration of investigational product.
- Lung transplantation anticipated during the study or within 90 days after the last administration of investigational product.
- Scheduled or planning to receive a vaccination that may cause increases in cytokine or chemokine levels (eg, influenza, human papillomavirus [HPV], or Coronavirus disease 2019 [COVID-19]) within the 28 days before administration of the first dose of investigational product or within 28 days after the last administration of investigational product in this study.
- Any other condition which, in the opinion of the investigator, may pose an additional risk to the study participant after the administration of investigational product.
- Received any investigational therapy within 28 days, or 5 drug half-lives whichever is longer, before randomization or intends to take an investigation therapy other than CSL312 during the study.
- Previously administered CSL312 in another interventional clinical study.
- Use of nintedanib or pirfenidone within 28 days before randomization (at any time, for any reason, and for any duration).
- Pregnant at Screening, or breastfeeding at Screening and not willing to cease breastfeeding.
- Female subject of childbearing potential or fertile male subject either not using or unwilling to use an acceptable method of contraception to avoid pregnancy during the study and for up to 90 days after the last administration of investigational product.
Acceptable methods of contraception:
- All female subjects are assumed to be of childbearing potential except:
- Subjects > 60 years of age.
- Subjects between the ages of 45 to 60 years, inclusive, with amenorrhea for ≥ 1 year with documented evidence of follicle-stimulating hormone (FSH) level > 30 IU/L. If the FSH level is not available before randomization, a serum pregnancy test is required at Screening. Urine pregnancy tests will also be required at the time points indicated in the Schedule of Assessments.
- Subjects who are surgically sterile for ≥ 3 months before providing informed consent.
- All male subjects are assumed fertile except subjects who are surgically sterile for ≥ 3 months before providing informed consent.
- Clinical evidence of active infection, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
- Current alcohol, drug, or medication abuse.
- Currently receiving a therapy not permitted during the study.
- Involved in the planning and / or conduct of the study (applies to CSL staff, staff at the study site, and third-party vendors).