NCT03712228

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Oct 2018

Typical duration for phase_2

Geographic Reach
5 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 17, 2018

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 19, 2018

Completed
10 days until next milestone

Study Start

First participant enrolled

October 29, 2018

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 15, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 15, 2021

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

November 8, 2022

Completed
Last Updated

November 8, 2022

Status Verified

October 1, 2022

Enrollment Period

3 years

First QC Date

October 17, 2018

Results QC Date

October 13, 2022

Last Update Submit

October 13, 2022

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (1)

  • The Mean Time Normalized Number of HAE Attacks Per Month in Subjects With C1-INH HAE During Treatment Period 1

    The time-normalized number of HAE attacks per month during Treatment Period 1 for a subject was calculated as the (number of HAE attacks / length of subject's evaluation period in days) \* 30.4375

    13 weeks

Secondary Outcomes (16)

  • The Number of Responder Subjects With C1-INH HAE During Treatment Period 1

    13 weeks

  • The Percentage of Responder Subjects With C1-INH HAE During Treatment Period 1

    13 weeks

  • The Number of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1

    13 weeks

  • The Percentage of HAE Attack-free Subjects With C1-INH HAE During Treatment Period 1

    13 weeks

  • The Number of Mild, Moderate or Severe HAE Attacks in Subjects With C1-INH HAE During Treatment Period 1

    13 weeks

  • +11 more secondary outcomes

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Subjects with C1-INH HAE receiving buffer only

Drug: Placebo

CSL312 (low)

ACTIVE COMPARATOR

Subjects with C1-INH HAE receiving low dose CSL312

Biological: Factor XIIa antagonist monoclonal antibody

CSL312 (med)

ACTIVE COMPARATOR

Subjects with C1-INH HAE receiving medium dose CSL312

Biological: Factor XIIa antagonist monoclonal antibody

CSL312 (high)

ACTIVE COMPARATOR

Subjects with C1-INH HAE receiving high dose CSL312

Biological: Factor XIIa antagonist monoclonal antibody

CSL312 (med/high)

ACTIVE COMPARATOR

Subjects with C1-INH HAE receiving medium/high dose CSL312

Biological: Factor XIIa antagonist monoclonal antibody

Interventions

Factor XIIa antagonist monoclonal antibodyBIOLOGICAL

Factor XIIa antagonist monoclonal antibody for intravenous and subcutaneous use

Also known as: CSL312
CSL312 (high)CSL312 (low)CSL312 (med)CSL312 (med/high)
PlaceboDRUG

Buffer without active ingredient

Placebo

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Donald S. Levy

Orange, California, 92868, United States

Location

Allergy & Asthma Clinical Research

Walnut Creek, California, 94598, United States

Location

Immunoe Health Centers

Centennial, Colorado, 80112, United States

Location

Institute for Asthma and Allergy

Chevy Chase, Maryland, 20815, United States

Location

The Mount Sinai Hospital

New York, New York, 10029, United States

Location

Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Allergy and Clinical Immunology McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

Ottawa Allergy Research Corp

Ottawa, Ontario, K1G 6C6, Canada

Location

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Universitätsklinikum Frankfurt Goethe-Universität

Frankfurt, 60590, Germany

Location

Hautklinik und Poliklinik der Universitätsklinik Mainz

Mainz, 55131, Germany

Location

HZRM Hämophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, 64546, Germany

Location

Barzilai University Medical Center

Ashkelon, 7830604, Israel

Location

Related Publications (3)

  • Craig TJ, Levy DS, Reshef A, Lumry WR, Martinez-Saguer I, Jacobs JS, Yang WH, Ritchie B, Aygoren-Pursun E, Keith PK, Busse P, Feuersenger H, Alexandru Bica M, Jacobs I, Pragst I, Magerl M. Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study. Lancet Haematol. 2024 Jun;11(6):e436-e447. doi: 10.1016/S2352-3026(24)00081-4. Epub 2024 May 3.

    PMID: 38710185DERIVED

  • 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.

    PMID: 36326435DERIVED

  • 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.

    PMID: 35219377DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

AngioedemaVascular DiseasesCardiovascular DiseasesHereditary Complement Deficiency DiseasesPrimary Immunodeficiency DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUrticariaSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System DiseasesImmunologic Deficiency Syndromes

Results Point of Contact

Title
Study Director
Organization
CSL Behring
clinicaltrials@cslbehring.com
610-878-4000

Study Officials

  • Study Director

    CSL Behring LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double blind
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: Subjects are assigned to 1 of 2 or more groups in parallel for the duration of the study
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 17, 2018

First Posted

October 19, 2018

Study Start

October 29, 2018

Primary Completion

October 15, 2021

Study Completion

October 15, 2021

Last Updated

November 8, 2022

Results First Posted

November 8, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations

IL(1)US(7)DE(4)CA(3)AU(1)