Clinical trial NCT03712228: A Study to Investigate CSL312 in Subjects With Hereditary Angioedema (HAE)
Official title: A Multicenter, Randomized, Placebo-controlled, Parallel-arm Study to Investigate the Efficacy, Pharmacokinetics, and Safety of CSL312 in Subjects With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hereditary Angioedema
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2018-10-19
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects are assigned to 1 of 2 or more groups in parallel for the duration of the study
Primary purpose: PREVENTION

Brief summary: This is a multicenter, randomized, placebo-controlled, parallel-arm, phase 2 study to investigate the clinical efficacy, pharmacokinetics, and safety of CSL312 as prophylaxis to prevent attacks in subjects with HAE.


Eligibility criteria: Inclusion Criteria:

* Male or female
* Aged ≥ 18 to ≤ 65 years
* A diagnosis of C1-INH HAE or FXII/PLG HAE;
* For subjects with C1-INH HAE: ≥ 4 HAE attacks over a consecutive 2-month period during the 3 months before Screening, as documented in the subject's medical record.

Exclusion Criteria:

* History of clinically significant arterial or venous thrombosis, or current clinically significant prothrombotic risk
* History of an uncontrolled, abnormal bleeding event due to a coagulopathy, or a current clinically significant coagulopathy or clinically significant risks for bleeding events
* Known incurable malignancies

Primary outcomes:
measure: The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
Secondary outcomes:
measure: The Number of Responder Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Percentage of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Mean Time-normalized Number of Mild, Moderate or Severe HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Number of Subjects With at Least One (1) HAE Attack Treated With On-demand HAE Medication, in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Percentage of Subjects With at Least One (1) HAE Attack Treated With On-demand HAE Medication, in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: Maximum Concentration (Cmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: Area Under the Concentration-time Curve in 1 Dosing Interval (AUC0-tau) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: Time of Maximum Concentration (Tmax) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: Terminal Elimination Half-life (T1/2) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: Clearance (CL/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: Volume of Distribution During the Elimination Phase (Vz/F) of CSL312 in Subjects With C1-INH HAE During Treatment Period 1
timeFrame: 13 weeks
measure: The Number of Subjects With C1-INH HAE With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI), Injection Site Reactions (ISRs), Binding Antibodies to CSL312 During Treatment Period 1
timeFrame: 13 weeks
Other outcomes:
Locations:
city: Orange
country: United States
facility: Donald S. Levy
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Centennial
country: United States
facility: Immunoe Health Centers
state: Colorado
city: Chevy Chase
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Hamilton
country: Canada
facility: Allergy and Clinical Immunology McMaster University
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Allergy Research Corp
state: Ontario
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt Goethe-Universität
city: Mainz
country: Germany
facility: Hautklinik und Poliklinik der Universitätsklinik Mainz
city: Mörfelden-Walldorf
country: Germany
facility: HZRM Hämophilie Zentrum Rhein Main GmbH
city: Ashkelon
country: Israel
facility: Barzilai University Medical Center
Study officials:
affiliation: CSL Behring LLC
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
citation: Craig T, Magerl M, Levy DS, Reshef A, Lumry WR, Martinez-Saguer I, Jacobs JS, Yang WH, Ritchie B, Aygoren-Pursun E, Keith PK, Busse P, Feuersenger H, Pawaskar D, Jacobs I, Pragst I, Doyle MK. Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022 Mar 5;399(10328):945-955. doi: 10.1016/S0140-6736(21)02225-X. Epub 2022 Feb 24.