Hereditary Angioedema
Conditions
Keywords
Autosomal dominant disease, Hereditary angioedema attack, Monoclonal antibody
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.
Interventions
BIOLOGICALGaradacimab
Participants will receive a loading dose of garadacimab, followed by once monthly garadacimab administration for 2 months. Garadacimab will be given as a subcutaneous injection. The timing for the administration of the loading dose (first administration of garadacimab) is determined by the dosing schedule of the current HAE prophylactic treatment. No washout necessary.
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to Day 95 (End of study [EoS]) |
| Percentage of Participants With TEAEs | Up to Day 95 (EoS) |
| Number of TEAEs | Up to Day 95 (EoS) |
| Rate of TEAEs per injection | Up to Day 95 (EoS) |
| Rate of TEAEs per participant year | Up to Day 95 (EoS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to Day 95 (EoS) | The AESIs for garadacimab are severe hypersensitivity including anaphylaxis. |
| 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 | Up to Day 95 (EoS) | — |
| 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 | Up to Day 95 (EoS) | — |
| 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 | Up to Day 95 (EoS) | — |
| 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 | Up to Day 95 (EoS) | — |
| Number of Participants with Anti-garadacimab Antibodies | Up to Day 95 (EoS) | — |
| Percentage of Participants with Anti-garadacimab Antibodies | Up to Day 95 (EoS) | — |
| Plasma Concentrations of Garadacimab | Up to Day 95 (EoS) | — |
| Percentage of Participants who Indicated Their Preference for Garadacimab | Up to Day 95 (EoS) | — |
Countries
Canada, Germany, United States
Contacts
STUDY_DIRECTORStudy Director
CSL Behring
Outcome results
None listed