CSL312 Safety, Pharmacokinetics, and Pharmacodynamics in Idiopathic Pulmonary Fibrosis

Study Overview
=================
Brief Summary
-----------------
This is a prospective, phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of CSL312 in subjects with idiopathic pulmonary fibrosis (IPF).

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of CSL312 in Subjects With Idiopathic Pulmonary Fibrosis

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Drug: CSL312
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients ≥ 40 years of age Documented diagnosis of IPF Exclusion Criteria: History of clinically significant cardiovascular disease, including myocardial infarction, unstable ischemic heart disease, congestive heart failure, or angina during the 6 months before screening Sinoatrial or atrioventricular block, uncontrolled hypertension Active bleeding or current clinically significant coagulopathy

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL312<br>Administered IV and SC | Drug: CSL312<br>* Fully human immunoglobulin G subclass 4/lambda recombinant monoclonal antibody<br>* Other names: Garadacimab;|
| Placebo Comparator: Placebo<br>Administered IV and SC | Drug: Placebo<br>* Same as the CSL312 formulation buffer<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent serious adverse events (SAEs) for CSL312 or placebo |  | Up to 22 weeks | 
| Percent of participants with SAEs for CSL312 or placebo |  | Up to 22 weeks | 
| Number of participants with treatment-emergent adverse events of special interest (AESIs) for CSL312 or placebo |  | Up to 22 weeks | 
| Percent of participants with AESIs for CSL312 or placebo |  | Up to 22 weeks | 
| Number of participants with treatment-emergent CSL312 induced antidrug antibodies (ADAs) |  | Up to 14 weeks | 
| Percent of participants with CSL312 induced ADAs |  | Up to 14 weeks | 
| Number of participants with treatment-emergent clinically significant abnormalities in laboratory assessments that are reported as adverse events (AEs) for CSL312 or placebo |  | Up to 14 weeks | 
| Percent of participants with treatment-emergent clinically significant abnormalities in laboratory assessments that are reported as adverse events (AEs) for CSL312 or placebo |  | Up to 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trough plasma concentration (Ctrough) after subcutaneous (SC) administration of CSL312 |  | Up to 14 weeks | 
| Maximum plasma concentration (Cmax) (last SC dosing interval only) of CSL312 |  | Up to 14 weeks | 
| Time to maximum plasma concentration (Tmax) (last SC dosing interval only) of CSL312 |  | Up to 14 weeks | 
| Area under the plasma concentration-time curve after the first dose interval (AUC0-tau) (last SC dosing interval only) of CSL312 |  | Up to 14 weeks | 
| Ctrough after intravenous (IV) administration of CSL312 |  | Up to 8 days | 
| Cmax after IV administration of CSL312 |  | Up to 8 days | 
| Tmax after IV administration of CSL312 |  | Up to 8 days | 
| Mean change from Baseline in FXIIa-mediated kallikrein activity of CSL312 |  | Up to 14 weeks | 
| Mean percentage of Baseline in FXIIa-mediated kallikrein activity of CSL312 |  | Up to 14 weeks |