A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-demand Treatment of Angioedema Attacks in Adults with Acquired Angioedema due to C1 Inhibitor Deficiency

Condition studied

Acquired Angioedema due to C1 Inhibitor Deficiency

Investigational medicinal product(s)

Eligibility

Primary endpoint

1. Part 1 Time-normalized (per 4 weeks) number of Investigator-confirmed AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase (Day 1 through Day 84), 2. Part 2 Time to symptom relief defined as PGI-C rating of at least ‘better’ sustained within 12 hours post-treatment, 3. Part 3 Incidence of TEAEs, treatment- emergent AESIs, and SAEs, 4. Part 3 Change from baseline in clinical laboratory, vital sign, physical examination, and electrocardiogram (ECG) parameters

Endpoint detail

1. Part 1 Proportion of participants who are AAE-C1INH attack-free during the 12-week Prophylaxis Treatment Phase, 2. Part 1 Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during the 12-week Prophylaxis Treatment Phase, 3. Part 1 Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase, 4. Part 1 Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase, 5. Part 1 Proportion of participants achieving ≥50% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase, 6. Part 1 Proportion of participants achieving ≥70% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase, 7. Part 1 Proportion of participants achieving ≥90% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase, 8. Part 1 Incidence of TEAEs, treatment-emergent AESIs, and SAEs, 9. Part 1 Change from baseline in clinical laboratory, vital sign, physical examination, and ECG parameters, 10. Part 1 Deucrictibant and deucrictibant metabolites pre-dose plasma concentrations at Week 6 and Week 12, 11. Part 1 Change from baseline in Angioedema Quality of Life (AE-QoL) total score, functioning domain score, and fears/shame domain score at Weeks 4, 8, and 12, 12. Part 1 Change from baseline in Angioedema Control Test 4-week version (AECT-4wk) at Week 12, 13. Part 1 Patient Global Assessment-Change (PGA-C) at Week 12 compared with Patient Global Assessment-Status (PGA-S) at baseline, 14. Part 1 Change from baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) at Week 12, 1. Part 2 Time to complete symptom resolution, defined as achieving Patient Global Impression of Severity (PGI-S) rating of “no symptoms” sustained within 24 hours post-treatment, 2. Part 2 Time to symptom relief defined as PGI-S rating of at least 1 point reduction sustained within 12 hours post-treatment, 3. Part 2 Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of “no symptoms” at 24 hours post-treatment, 4. Part 2 Time to onset of symptom relief, defined as PGI-C rating of at least “a little better” sustained within 12 hours post-treatment, 5. Part 2 Time to End of Progression (EoP) in attack symptoms within 12 hours, with EoP time defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved, 6. Part 2 Incidence of TEAEs, treatment-emergent AESIs, and SAEs, 7. Part 2 Change from baseline in clinical laboratory, vital sign, physical examination, and ECG parameters, 8. Part 2 Deucrictibant and deucrictibant metabolites plasma concentration-time profiles, 1. Part 3 Time to symptom relief, defined as PGI-C rating of at least “better” sustained within 12 hours post-treatment, 2. Part 3 Time to symptom relief, defined as PGI-S rating of at least 1 point reduction sustained within 12 hours post-treatment, 3. Part 3 Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of “no symptoms” at 24 hours post-treatment, 15. Part 1 Deucrictibant and deucrictibant metabolites urine concentrations at Week 12