This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of once-daily orally administered deucrictibant extended-release tablet compared to placebo for prophylaxis to prevent angioedema attacks in participants aged ≥ 12 years with hereditary angioedema.
The study consists of a Screening Period during which eligibility is confirmed, a Treatment Period of 24 weeks, and a Follow-up Period of maximum 4 weeks or subjects may roll over into the open-label study PHA022121-C307 (CHAPTER-4). During the Treatment period participants will receive blinded study drug (deucrictibant or placebo randomized in a 2:1 ratio). Participants will undergo regular efficacy and safety assessments, complete an electronic diary daily, and also complete questionnaires at predefined timepoints during the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
81
Deucrictibant 40mg extended-release tablet for once daily oral use
Placebo
Time-normalized (per 4 weeks) number of Investigator-confirmed HAE attacks during the 24-week Treatment Period
Time frame: 24 weeks
Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the 24-week Treatment Period
Time frame: 24 weeks
Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during the 24-week Treatment Period
Time frame: 24 weeks
Time-normalized number of Investigator-confirmed severe HAE attacks during the 24-week Treatment Period
Time frame: 24 weeks
Proportion of participants achieving ≥50% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period
Time frame: 24 weeks
Proportion of participants achieving ≥70% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period
Time frame: 24 weeks
Proportion of participants achieving ≥90% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period
Time frame: 24 weeks
Proportion of participants that are HAE attack-free during the 24-week Treatment Period
Time frame: 24 weeks
Proportion of time without angioedema symptoms during the 24-week Treatment Period
Time frame: 24 weeks
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
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Study Site
Little Rock, Arkansas, United States
Study Site
San Diego, California, United States
Study site
Santa Monica, California, United States
Study site
Walnut Creek, California, United States
Study Site
Chevy Chase, Maryland, United States
Study Site
St Louis, Missouri, United States
Study Site
Corrientes, Argentina
Study Site
San Martin, Argentina
Study Site
Santo André, Brazil
Study Site
Sofia, Bulgaria
...and 46 more locations
Time frame: Up to 38 weeks
Pharmacokinetics [PK]: Deucrictibant plasma concentration time profiles
Time frame: 24 weeks
Patient reported outcome: Angioedema Quality of Life (AE-QoL) questionnaire
The AE-QoL is a short 17-item questionnaire designed to retrospectively assess HRQoL, with a recall period of 4 weeks. Its results can be displayed as a total score or as 4 domain scores. The scores range from 0 to 100, after linear transformation of raw values, with higher scores indicating higher HRQoL impairment.
Time frame: 24 weeks
Patient reported outcome: Patient Global Assessment of Change (PGA-Change)
PGA-Change assesses on a 5-point scale how the participant's QoL has been impacted by HAE since start taking the study drug
Time frame: 24 weeks
Patient reported outcome: Angioedema Control Test 4-week version (AECT-4wk)
AECT-4wk measures disease control retrospectively, it comprises 4 questions over a 4-week recall period. Scores for the responses in the AECT range from 0 to 16, with higher scores indicating better disease control (≤ 9 poorly controlled; ≥ 10 well controlled)
Time frame: 24 weeks
Patient reported outcome: Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)
WPAI-SHP is a questionnaire assessing how a health condition impacts a person's ability to work and do regular activities and it includes 4 domains. Scores indicate the percentage of time the patient missed work or was less productive owing to HAE-related complications.
Time frame: Up to 34 weeks
Patient reported outcome: Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)
TSQM-9 is a 9-item questionnaire evaluating patient treatment satisfaction and it includes 3 domains. Scoring is by domain and each domain score is computed by summing the individual TSQM items in each domain and then transforming the composite score into a value ranging from 0 to 100, with higher scores indicating higher satisfaction.
Time frame: Up to 34 weeks