Prospective, multicenter, randomized, double-blind, parallel group, placebo- controlled, efficacy and safety phase 3 study of an intravenous human plasma- derived C1 esterase inhibitor (C1-INH) concentrate in participants with congenital C1-INH deficiency for the treatment and pre-procedure prevention of acute hereditary angioedema attacks
Is at least 18 years of age (applicable for 1st study phase) or is at least 2 years of age (applicable for 2nd study phase)
Has confirmed diagnosis of HAE type I or II
Has had at least 3 moderate or severe HAE attacks (excluding extremity attacks) in the last 3 months before the Screening Visit. For participants ≥2 and ≤12 years of age, has had at least 1 moderate or severe HAE attack (excluding extremity attacks) in the last 6 months before Screening Visit
Has a documented congenital C1-INH functional activity <50% with or without C1-INH deficiency and C4 antigen level below the laboratory reference range
Has a history of clinically relevant antibody development against C1-INH
Has a medical history consistent with Type 3 HAE (i.e., onset at age above 40 year, no family history, no known HAE mutation, low C1q level in plasma)
Has a history of allergic reaction to C1-INH or other blood/plasma product
Has a history of B-cell malignancy that was unresolved in the past 5 years
Parallel
OCTA-C1-INH
DrugOCTA-C1-INH is a stable, sterile, virus-inactivated, nano-filtered, highly purified concentrate of human C1-INH prepared from pooled human plasma. After reconstitution in 2.5mL water for injection, the solution can be administered as a slow IV injection. OCTA-C1-INH is given as a dose of 20 IU/kg body weight (BW)
Placebo
Other intervention0.1 mL/kg BW 0.9% sodium chloride injection
Time (h) to beginning of unequivocal symptom relief at the defining site in blinded participants.
Patient will rate symptom relief for the defining attack site (site of swelling or pain) from 15 minutes after start of the IMP injection every 15 minutes over 4 hours. Unequivocal relief is defined as having 3 consecutive reports of "absent now but present before," "absent now and absent before", or "present, symptoms better" on the 5-grade SRRS. This measure will also be used for the secondary outcomes in a different context.
Percentage of participants responding to treatment
Percentage of patients responding to treatment, defined as beginning of unequivocal symptom relief at the defining site within 4 hours after injection (once per participant after first qualifying attack in the study). Unequivocal relief is defined as having 3 consecutive reports of "absent now but present before," "absent now and absent before", or "present, symptoms better" on the 5-grade symptom relief rating.
Time to beginning of unequivocal symptom relief at all sites involved
Time to the beginning of unequivocal symptom relief at all sites involved within 4 hours after injection. Unequivocal relief is defined as having 3 consecutive reports of "absent now but present before," "absent now and absent before", or "present, symptoms better" on the 5-grade symptom relief rating.
Changes in symptom severity at the defining site by VAS severity rating
Changes in symptom severity at the defining site by visual analog scale (VAS) rating from pre-injection over 4 hours after injection. The VAS is a self-reported 0-100 pain and swelling rating scale.