Clinical trial NCT06806657: Safety Study in Subjects ≥ 12 Years of Age With Hereditary Angioedema Switching to Garadacimab
Official title: A Phase 4 Open-label Study to Evaluate the Safety After Switching to CSL312 (Garadacimab) From Current Prophylactic HAE Treatment in Subjects With HAE ≥ 12 Years of Age
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hereditary Angioedema
Keywords: Autosomal dominant disease
Hereditary angioedema attack
Monoclonal antibody
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2025-02-04
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study is designed to evaluate the safety after switching to garadacimab from another prophylactic hereditary angioedema (HAE) treatment (marketed kallikrein \[KK\] inhibitor or plasma-derived C1-esterase inhibitor \[pdC1INH\]prophylactic) when administered once monthly for approximately 3 months in participants aged greater than or equal to (\>=) 12 years with HAE.


Eligibility criteria: Inclusion Criteria:

* Aged \>= 12 years at the time of providing written informed consent / assent.
* Have a history of response to on-demand HAE treatment for the treatment of acute HAE attacks.
* Documented laboratory diagnosis in medical records of C1-esterase inhibitor hereditary angioedema (HAE-C1INH) type 1 or type 2:

  * Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria),
  * C1-esterase inhibitor (C1INH) antigen concentration or functional activity less than (\<) 50% of normal as documented in the participant's medical record, or
  * C4-antigen concentration below the lower limit of the reference range as documented in the participant's medical record.

For HAE-nC1INH: Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria); an HAE-associated FXII gene mutation (eg, FXII point mutation Thr328Lys or Thr328Arg, or deletion of 72 base pairs \[c.971_1018 + 24del72\], or duplication of 18 base pairs \[c.892-909dup\]), as documented in the participant's medical record, OR an HAE-associated plasminogen gene mutation (PLG) gene mutation (eg, PLG point mutation Lys330Glu), as documented in the participant's medical record; C1INH antigen concentration or functional activity 70 to 120% of the normal level, as documented in the participant's medical record.

• Use of lanadelumab, berotralstat, or pdC1INH for the prophylactic treatment of HAE and be on a stable (consistent) dose / regimen of such medication for at least 3 months prior to Screening.

Exclusion Criteria:

* Concomitant diagnosis of another form of angioedema, such as idiopathic or acquired angioedema or recurrent angioedema associated with urticaria.
* Use of androgens, antifibrinolytics, or investigational products (other than garadacimab) for routine prophylaxis against HAE attacks.
* Known or suspected hypersensitivity to monoclonal antibody therapy or hypersensitivity to the active substance (garadacimab) or to any of the excipients.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 95 (End of study [EoS])
measure: Percentage of Participants With TEAEs
timeFrame: Up to Day 95 (EoS)
measure: Number of TEAEs
timeFrame: Up to Day 95 (EoS)
measure: Rate of TEAEs per injection
timeFrame: Up to Day 95 (EoS)
measure: Rate of TEAEs per participant year
timeFrame: Up to Day 95 (EoS)
Secondary outcomes:
measure: Number of Participants With: Serious Adverse Events (SAEs), Deaths, Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and Adverse Events of Special Interest (AESI)
timeFrame: Up to Day 95 (EoS)
measure: Percentage of Participants With: SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and AESI
timeFrame: Up to Day 95 (EoS)
measure: Number of SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, AESI and Laboratory Findings Reported as an AE, and AESI
timeFrame: Up to Day 95 (EoS)
measure: Rate per injection of: SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and AESI
timeFrame: Up to Day 95 (EoS)
measure: Rate per participant year of: SAEs, Deaths, Treatment Related TEAEs, TEAEs leading to study discontinuation, TEAEs by severity, Laboratory Findings Reported as an AE, and AESI
timeFrame: Up to Day 95 (EoS)
measure: Number of Participants with Anti-garadacimab Antibodies
timeFrame: Up to Day 95 (EoS)
measure: Percentage of Participants with Anti-garadacimab Antibodies
timeFrame: Up to Day 95 (EoS)
measure: Plasma Concentrations of Garadacimab
timeFrame: Up to Day 95 (EoS)
measure: Percentage of Participants who Indicated Their Preference for Garadacimab
timeFrame: Up to Day 95 (EoS)
Other outcomes:
Locations:
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona
state: Arizona
city: Orange
country: United States
facility: Donald Levy M.D.
state: California
city: Santa Monica
country: United States
facility: Raffi Tachdjian MD, Inc.
state: California
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC
state: Ohio
Study officials:
affiliation: CSL Behring
name: Study Director
role: STUDY_DIRECTOR
References: