Study of Oral 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

Phase 3RecruitingNCT07266805

Pharvaris Netherlands B.V.48 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 soft 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 soft 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)

Interventions

DeucrictibantDRUG

Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use

PlaceboDRUG

Part 1: Placebo Comparator tablet for once daily oral use

DeucrictibantDRUG

Part 2: Deucrictibant 20 mg soft capsule oral use

PlaceboDRUG

Part 2: Placebo Comparator soft capsule oral use

DeucrictibantDRUG

Part 3: Deucrictibant 20 mg soft capsule oral use

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. * If underlying disease associated with AAE is present, the underlying disease must be stable throughout the duration of part 1. * 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 (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). * Receiving long-term prophylaxis (LTP) treatment for AAE-C1INH and satisfied with this treatment. Participants who are not satisfied (eg, tolerability issues, lack of efficacy) and have previously stopped LTP treatment for AAE-C1INH, for reasons other than participation in this study, can sign the ICF and begin the Screening Period only if their 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 (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit

Locations (32)

Study Site

San Diego, California, United States

RECRUITING

Study Site

Walnut Creek, California, United States

RECRUITING

Study Site

St Louis, Missouri, United States

RECRUITING

Study Site

Hershey, Pennsylvania, United States

RECRUITING

Study Site

Clayton, Australia

RECRUITING

Study Site

Vienna, Austria

RECRUITING

Study Site

Sofia, Bulgaria

RECRUITING

Study Site

Edmonton, Canada

RECRUITING

Study Site

Grenoble, France

RECRUITING

Study Site

Lille, France

RECRUITING

...and 22 more locations

Outcomes

Primary Outcomes

Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase

Time frame: 12 weeks

Part 2: Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"

Time frame: 12 hours post-treatment

Part 3: Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (AESIs), and serious adverse events (SAEs)