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 (CREAATE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)
• Intervention / Treatment: Drug: Deucrictibant; Drug: Deucrictibant; Drug: Deucrictibant; Drug: Placebo; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pharvaris Clinical Team; Phone Number: 0031-712-036-410; Email: clinicaltrials@pharvaris.com

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • Recruiting
    • Study Site
• Canada
  • Edmonton, Canada
    • Recruiting
    • Study Site
• France
  • Paris, France
    • Recruiting
    • Study Site
• Germany
  • Berlin, Germany
    • Recruiting
    • Study Site
  • Frankfurt am Main, Germany
    • Recruiting
    • Study Site
  • Munich, Germany
    • Recruiting
    • Study Site
• Hungary
  • Budapest, Hungary
    • Recruiting
    • Study Site
• Italy
  • Milan, Italy
    • Recruiting
    • Study List
• Switzerland
  • Basel, Switzerland
    • Recruiting
    • Study Site
• United Kingdom
  • Cambridge, United Kingdom
    • Recruiting
    • Study Site
  • Leicester, United Kingdom
    • Recruiting
    • Study Site
  • London, United Kingdom
    • Recruiting
    • Study Site
  • Newcastle upon Tyne, United Kingdom
    • Recruiting
    • Study Site
  • Plymouth, United Kingdom
    • Recruiting
    • Study Site
• United States
  • California
    • Walnut Creek, California, United States, 94598
      • Recruiting
      • Study Site
    • Walnut Creek, California, United States, 94598,
      • Recruiting
      • Study Site
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Recruiting
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - Arm 1 - Active	Drug: Deucrictibant; Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use; Drug: Deucrictibant; Part 2: Deucrictibant 20 mg soft capsule oral use; Drug: Deucrictibant; Part 3: Deucrictibant 20 mg soft capsule oral use
Placebo Comparator: Part 1 - Arm 2 - Placebo	Drug: Placebo; Part 1: Placebo Comparator tablet for once daily oral use; Drug: Placebo; Part 2: Placebo Comparator soft capsule oral use
Experimental: Part 2 - Arm 1	Drug: Deucrictibant; Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use; Drug: Deucrictibant; Part 2: Deucrictibant 20 mg soft capsule oral use; Drug: Deucrictibant; Part 3: Deucrictibant 20 mg soft capsule oral use; Drug: Placebo; Part 1: Placebo Comparator tablet for once daily oral use; Drug: Placebo; Part 2: Placebo Comparator soft capsule oral use
Experimental: Part 2 - Arm 2	Drug: Deucrictibant; Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use; Drug: Deucrictibant; Part 2: Deucrictibant 20 mg soft capsule oral use; Drug: Deucrictibant; Part 3: Deucrictibant 20 mg soft capsule oral use; Drug: Placebo; Part 1: Placebo Comparator tablet for once daily oral use; Drug: Placebo; Part 2: Placebo Comparator soft capsule oral use
Experimental: Part 3 - Open-label	Drug: Deucrictibant; Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use; Drug: Deucrictibant; Part 2: Deucrictibant 20 mg soft capsule oral use; Drug: Deucrictibant; Part 3: Deucrictibant 20 mg soft capsule oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 (Prophylaxis, Double-blind Treatment Phase)	Time-normalized number of Investigator-confirmed AAE attacks during Treatment Phase	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"	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	Through study completion, an average of 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 (Prophylaxis, Double-blind Treatment Phase)	Proportion of participants who are AAE attack-free during Treatment Phase	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	12 weeks
Part 1 (Prophylaxis, Double-blind Treatment Phase)	Time-normalized number of Investigator-confirmed moderate or severe AAE attacks during Treatment Phase	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	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.	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	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)	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)	From enrollment through end of Part 1 (Week 12)
Part 2 (On-demand, Double-blind Treatment Phase)	Time to symptom relief defined as PGI-S rating of at least 1 point reduction	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	12 weeks
Part 1 (Prophylaxis, Double-blind Treatment Phase)	Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites and urine plasma concentrations	12 weeks
Part 2 (On-demand, Double-blind Treatment Phase)	Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms	sustained within 24 hours post-treatment
Part 2 (On-demand, Double-blind Treatment Phase)	Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 3 (On-demand, Open-label Extension Treatment Phase)	Time to symptom relief, as PGI-C rating of at least "better"	12 hours post-treatment

Collaborators and Investigators

• Sponsor: Pharvaris Netherlands B.V.
• Investigators: Study Director: Study Director, Pharvaris, Pharvaris Netherlands B.V.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 20, 2025
• First Submitted That Met QC Criteria: November 25, 2025
• First Posted (Actual): December 5, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Prophylaxis; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHA121; Angioedema; On-demand; Pharvaris; deucrictibant; Acquired Angioedema-C1-INH; AAE-C1-INH; C1-Inhibitor Deficiency; Acquired; Acquired angioedema
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary; Acquired angioedema
• Other Study ID Numbers: PHA022121-C308

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No