Garadacimab Safety, Pharmacokinetics, and Pharmacodynamics in Idiopathic Pulmonary Fibrosis

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

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 garadacimab in subjects with idiopathic pulmonary fibrosis (IPF).

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Garadacimab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Royal Adelaide Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Univerität Graz
  • Linz, Austria, 4021
    • Kepler Universitätsklinikum
• Belgium
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis (Uz) Leuven
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire Sart Tilman
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • Windsor, Ontario, Canada, N8X 1T3
      • Dr. Syed Anees Medicine Professional Corporation
• Denmark
  • Odense, Denmark, 5000
    • Odense Universitetshospital - Lungemedicinsk Forskningsenhed
• Germany
  • Coswig, Germany, 01640
    • Fachkrankenhaus Coswig GmbH
  • Essen, Germany, 45239
    • Universitaetsklinikum Essen - Ruhrlandklinik (Westdeutsches Lungenzentrum)
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover - Klinik für Pneumologie
  • Wuppertal, Germany, 42283
    • Petrus Krankenhaus Wuppertal
• Italy
  • Foggia, Italy, 71122
    • Azienda Ospedaliera Universitaria Ospedali Riuniti Foggia
• Poland
  • Białystok, Poland, 15-044
    • Centrum Medycyny Oddechowej Bialymstoku
  • Nowa Sol, Poland, 67-100
    • Twoja Przychodnia Centrum Medyczne Nowa Sol
  • Wrocław, Poland, 51-162
    • Centrum Badań Klinicznych NZOZ
• Spain
  • Barcelona, Spain, 08006
    • Giromed Institute, SLP
  • Cadiz, Spain, 11009
    • Hospital Universitario Puerta del Mar (HUPM)
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth Hospital
  • Londonderry, United Kingdom, BT47 6SB
    • Altnagelvin Area Hospital
  • Manchester, United Kingdom, M23 9LT
    • Manchester Univ NHS - Wythenshawe Hospital
  • MD
    • Oxford, MD, United Kingdom, OX3 7LE
      • The Churchill Hospital - Oxford University Hospitals NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • The University of Alabama at Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates Clinical Trials AZ
  • California
    • Huntington Beach, California, United States, 92647
      • National Institute of Clinical Research
    • Los Angeles, California, United States, 90033
      • University of Southern California - Center for Advanced Lung Disease
    • Orange, California, United States, 92868
      • University of California Irvine
  • Florida
    • Brandon, Florida, United States, 33511
      • Meris Clinical Research
    • Miami, Florida, United States, 33165
      • Reliant Medical Research
    • Miami, Florida, United States, 33175
      • US Associates in Research LLC
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
    • Ocala, Florida, United States, 34471
      • Renstar Medical Research
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group, PA
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Jadestone Clinical Research
  • Missouri
    • Hannibal, Missouri, United States, 63401
      • Hannibal Clinic
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical Center
  • North Carolina
    • Smithfield, North Carolina, United States, 27577
      • Superior Clinical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University TMS
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Clinical Trial Center of Middle Tennesse
  • Texas
    • Dallas, Texas, United States, 75235
      • Southwest Family Medicine Associates
    • Dallas, Texas, United States, 75230
      • Elite Medical Research
    • Dallas, Texas, United States, 75246
      • Baylor Scott and White Health - Advanced Lung Disease Specialists
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Administered IV and SC	Drug: Placebo; Participants received a matching placebo IV loading dose, followed by 3 SC doses.
Experimental: Garadacimab; Administered IV and SC	Drug: Garadacimab; Participants received garadacimab intravenous (IV) loading dose followed by 3 subcutaneous (SC) doses.; Other Names: Factor XIIa antagonist monoclonal antibody; CSL312

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent (TE) Serious Adverse Events (SAEs)	A TE SAE is defined as an SAE reported at or after the start of the first administration of study treatment. A SAE is defined as any untoward medical occurrence that at any dose results in: death, life-threatening event, initial or prolongation of existing hospitalization, disability or incapacity, congenital anomaly or birth defect, or any other medically significant event.	Up to 22 weeks
Percentage of Participants With TE SAEs	A TE SAE is defined as an SAE reported at or after the start of the first administration of study treatment. A SAE is defined as any untoward medical occurrence that at any dose results in: death, life-threatening event, initial or prolongation of existing hospitalization, disability or incapacity, congenital anomaly or birth defect, or any other medically significant event	Up to 22 weeks
Number of Participants With TE Adverse Events of Special Interests (AESIs)	The following TEAEs were considered as AESIs: Bleeding events that were abnormal in the opinion of the Investigator, Thromboembolic events (non-systemic thrombosis [e.g., localized thrombosis associated with vascular access] was not considered an AESI), and Severe hypersensitivity including anaphylaxis.	Up to 22 weeks
Percentage of Participants With TE-AESIs	The following TEAEs were considered as AESIs: Bleeding events that were abnormal in the opinion of the Investigator, Thromboembolic events (non-systemic thrombosis [e.g., localized thrombosis associated with vascular access] was not considered an AESI), and Severe hypersensitivity including anaphylaxis.	Up to 22 weeks
Number of Participants With Garadacimab Induced Anti Drug Antibodies (ADAs) in Plasma		At Day 36 and Day 92 after the first treatment
Percentage of Participants With Garadacimab Induced ADAs in Plasma		At Day 36 and Day 92 after the first treatment
Number of Participants With TE Clinically Significant Abnormalities in Laboratory Assessments Reported as Adverse Events (AEs)		Up to 14 weeks after treatment
Percentage of Participants With TE Clinically Significant Abnormalities in Laboratory Assessments Reported as AEs		Up to 14 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Plasma Concentration (Ctrough) After SC Administration of Garadacimab		At Day 36 and Day 64
Maximum Plasma Concentration (Cmax) (Last SC Dosing Interval Only) of Garadacimab		After dosing on Day 64
Time to Maximum Plasma Concentration (Tmax) (Last SC Dosing Interval Only) of Garadacimab		After dosing on Day 64
Area Under the Plasma Concentration-time Curve Over the Dose Interval (AUC0-tau) (Last SC Dosing Interval Only) of Garadacimab		After dosing on Day 64
Ctrough After IV Administration of Garadacimab		At Day 8
Cmax After IV Administration of Garadacimab		After dosing on Day 1
Tmax After IV Administration of Garadacimab		After dosing on Day 1
Mean Change From Baseline in FXIIa-mediated Kallikrein Activity		Baseline and at Day 92
Mean Percentage of Baseline in FXIIa-mediated Kallikrein Activity	Percent baseline is calculated by using the formula visit value / baseline value multiplied by 100, percent baseline is reported as percentage in the outcome measure.	Baseline and at Day 92

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2022
• Primary Completion (Actual): January 2, 2024
• Study Completion (Actual): January 2, 2024

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
• Other Study ID Numbers: CSL312_2002; 2021 003162 12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No