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

Official title

A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant Extended-release (XR) Tablet for Prophylaxis and Deucrictibant Immediate-release (IR) Capsule for On-demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency

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.

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

• Drug Deucrictibant
  Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use
• Drug Placebo
  Part 1: Placebo Comparator tablet for once daily oral use
• Drug Deucrictibant
  Part 2: Deucrictibant 20 mg soft capsule oral use
• Drug Placebo
  Part 2: Placebo Comparator soft capsule oral use
• Drug Deucrictibant
  Part 3: Deucrictibant 20 mg soft capsule oral use

Primary outcome measures

• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: 12 weeks]
• Part 2 (On-demand, Double-blind Treatment Phase) [Time frame: 12 hours post-treatment]
• Part 3 (On-demand, Open-label Extension Treatment Phase) [Time frame: Through study completion, an average of 36 weeks]

Secondary outcome measures (12)

• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: 12 weeks]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: From enrollment through end of Part 1 (Week 12)]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: From enrollment through end of Part 1 (Week 12)]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: From enrollment through end of Part 1 (Week 12)]
• Part 1 (Prophylaxis, Double-blind Treatment Phase) [Time frame: From enrollment through end of Part 1 (Week 12)]
• Part 2 (On-demand, Double-blind Treatment Phase) [Time frame: sustained within 24 hours post-treatment]
• Part 2 (On-demand, Double-blind Treatment Phase) [Time frame: 12 hours post-treatment]
• Part 2 (On-demand, Double-blind Treatment Phase) [Time frame: 12 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United Kingdom · 6 centers

• Study Site — Bristol
• Study Site — Cambridge
• Study Site — Leicester
• Study Site — London
• Study Site — Newcastle upon Tyne
• Study Site — Plymouth

Italy · 5 centers

• Study Site 1 — Milan
• Study Site 2 — Milan
• Study Site 3 — Milan
• Study Site — Padova
• Study Site — Roma

United States · 4 centers

• Study Site — San Diego
• Study Site — Walnut Creek
• Study Site — St Louis
• Study Site — Hershey

France · 3 centers

• Study Site — Grenoble
• Study Site — Lille
• Study Site — Paris

Germany · 3 centers

• Study Site — Berlin
• Study Site — Frankfurt am Main
• Study Site — Munich

Australia · 1 center

• Study Site — Clayton

Austria · 1 center

• Study Site — Vienna

Bulgaria · 1 center

• Study Site — Sofia

Canada · 1 center

• Study Site — Edmonton

Hungary · 1 center

• Study Site — Budapest

Netherlands · 1 center

• Study Site — Amsterdam

New Zealand · 1 center

• Study Site — Auckland

Poland · 1 center

• Study Site — Krakow

Spain · 1 center

• Study Site — Madrid

Switzerland · 1 center

• Study Site — Basel

Turkey (Türkiye) · 1 center

• Study Site — Ankara

Identifiers

NCT: NCT07266805 · PHA022121-C308

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗