Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant IR Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency

Phase 3RecruitingNCT07266805

Pharvaris Netherlands B.V.32 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Time-normalized number of Investigator-confirmed AAE attacks during Treatment Phase

Time frame: 12 weeks

Part 2 (On-demand, Double-blind Treatment Phase)

Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"

Time frame: 12 hours post-treatment

Part 3 (On-demand, Open-label Extension Treatment Phase)

Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation

Time frame: Through study completion, an average of 36 weeks

Secondary Outcomes

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Proportion of participants who are AAE attack-free during Treatment Phase

Time frame: 12 weeks

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Time-normalized number of Investigator-confirmed AAE attacks treated with on-demand medication during Treatment Phase

Time frame: 12 weeks

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Time-normalized number of Investigator-confirmed moderate or severe AAE attacks during Treatment Phase

Time frame: 12 weeks

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Safety endpoints: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation

Time frame: 12 weeks

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Pharmacokinetics \[PK\]: Deucrictibant and deucrictibant metabolites and urine plasma concentrations

Time frame: 12 weeks

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Patient reported outcomes: · 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: From enrollment through end of Part 1 (Week 12)

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Patient reported outcomes: · 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: From enrollment through end of Part 1 (Week 12)

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Patient reported outcomes: · 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: From enrollment through end of Part 1 (Week 12)

Part 1 (Prophylaxis, Double-blind Treatment Phase)

Patient reported outcomes: · EuroQol 5 Dimension 5 level (EQ 5D 5L) EQ 5D 5L is a brief, multiattribute, generic, health status measure composed of 5 questions with Likert response options (descriptive system) and a visual analog scale (EQ-VAS). The latter asks patients to rate their own health from 0 to 100 (the worst and best imaginable health, respectively)

Time frame: From enrollment through end of Part 1 (Week 12)

Part 2 (On-demand, Double-blind Treatment Phase)

Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms

Time frame: sustained within 24 hours post-treatment

Part 2 (On-demand, Double-blind Treatment Phase)

Time to symptom relief defined as PGI-S rating of at least 1 point reduction

Time frame: 12 hours post-treatment

Part 2 (On-demand, Double-blind Treatment Phase)

Safety endpoints: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation

Time frame: 12 weeks

Part 2 (On-demand, Double-blind Treatment Phase)

Pharmacokinetics \[PK\]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles

Time frame: Day 1

Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant IR Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts