Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)
Conditions
Keywords
Acquired Angioedema-C1-INH, AAE-C1-INH, Oral Treatment, deucrictibant, Prophylaxis, On-demand, C1-Inhibitor Deficiency, PHA121, Pharvaris, Bradykinin B2 Receptor Antagonists, Angioedema, Acquired, Acquired angioedema
Brief summary
This is a Phase 3, multicenter, 3-part study, with 2 randomized, double-blind, placebo-controlled parts and an open-label extension part, to evaluate the efficacy and safety of orally administered deucrictibant XR tablet for prophylaxis, and deucrictibant IR capsule for on-demand treatment of angioedema attacks in adult participants aged ≥ 18 years with AAE-C1INH.
Detailed description
The study consists of a Screening Period, during which eligibility is confirmed, a Part 1 Prophylaxis Double-blind Treatment Phase, a Part 2 On-demand, Double-blind Treatment Phase, and a Part 3 On-demand Open-label Extension Phase. Approximately 24 participants will be randomized in Part 1 into 2 parallel arms for a treatment period of 12 weeks. During the prophylaxis treatment period participants will receive blinded study drug (deucrictibant 40 mg XR or placebo randomized in a 1:1 ratio). Upon completion of Part 1, participants will roll-over into Part 2. In addition to rollover participants completing Part 1, new deucrictibant treatment-naïve participants will be enrolled directly into Part 2 and this may occur while Part 1 is ongoing. During the on-demand period participants will receive blinded study drug (deucrictibant 20 mg IR capsule or matching placebo randomized in a 1:1 ratio, 2-period, 2-treatment crossover design) for 2 qualifying AAE-C1INH attacks. Participants completing Part 2 may roll over into Part 3 where all AAE-C1INH attacks will be treated with open-label deucrictibant 20 mg soft capsule.
Interventions
DRUGDeucrictibant
Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use
DRUGPlacebo
Part 1: Placebo Comparator tablet for once daily oral use
Sponsors
Pharvaris Netherlands B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1 is parallel Part 2 is crossover Part 3 is single group
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent * Male or female (sex at birth) aged ≥18 years * Diagnosis of AAE-C1INH * History of AAE-C1INH attacks prior to the Screening Visit: * Participants enrolling in Part 1 must have stable underlying disease of AAE-C1INH * The underlying condition can reasonably be expected to remain stable for the duration * Reliable access and ability to use available therapy to effectively manage AAE- C1INH attacks. * Female participants of childbearing potential must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method. Females of non-childbearing potential (prepubertal, surgically sterile, or postmenopausal with ≥ 12 months amenorrhea and postmenopausal FSH confirmation) are not required to use contraception during the study. • Capable of recording, without assistance, eDiary and ePRO data using an electronic device, as evidenced by the eDiary and ePRO training.
Exclusion criteria
* Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at the Screening Visit (whichever is longer). * Participants who have previously received prophylactic therapy but have stopped can participate in this study provided the last dose of the treatment was received prior to the timepoint before the Screening Visit * Any females who are pregnant, plan to become pregnant, or are currently breast-feeding * Abnormal hepatic function * Moderate or severe renal impairment * Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study. * History of epilepsy and/or other significant neurological diseases * Any clinically significant and uncontrolled gastrointestinal dysfunction that may impact study drug absorption * Evidence of current alcohol or drug abuse * Use of medications that are moderate and strong inhibitors of cytochrome P450 (CYP) 3A4, or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) at the time of the Screening Visit * Known hypersensitivity to deucrictibant or any of the excipients of the study drug * Use of angiotensin-converting enzyme inhibitors or any estrogen-containing medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (Prophylaxis, Double-blind Treatment Phase) | 12 weeks | Time-normalized number of Investigator-confirmed AAE attacks during Treatment Phase |
| Part 2 (On-demand, Double-blind Treatment Phase) | 12 hours post-treatment | Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better" |
| Part 3 (On-demand, Open-label Extension Treatment Phase) | Through study completion, an average of 36 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 (Prophylaxis, Double-blind Treatment Phase) | 12 weeks | Proportion of participants who are AAE attack-free during Treatment Phase |
| Part 2 (On-demand, Double-blind Treatment Phase) | sustained within 24 hours post-treatment | Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms |
Countries
Australia, Austria, Bulgaria, Canada, France, Germany, Hungary, Italy, Netherlands, New Zealand, Poland, Spain, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTPharvaris Clinical Team
STUDY_DIRECTORStudy Director, Pharvaris
Pharvaris Netherlands B.V.
Outcome results
None listed