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

NCT07266805 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: PHA022121-C308
• Study Type: interventional
• Target: 48
• Locations: 15 countries
• Sites: 31

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 soft capsule for on-demand treatment of angioedema attacks in adult participants aged ≥ 18 years with AAE-C1INH.

Conditions

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

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

Outcome Measures

Primary Outcomes (9)

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

  12 weeks

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

  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)

  Through study termination, an average of 36 weeks

• Part 3: Number of participants with clinically significant changes from baseline in Hematology parameters

  Through study termination, an average of 36 weeks

• Part 3: Number of participants with clinically significant changes from baseline in Urinalysis parameters

  Through study termination, an average of 36 weeks

• Part 3: Number of participants with clinically significant changes from baseline in Biochemistry parameters

  Through study termination, an average of 36 weeks

• Part 3: Number of participants with clinically significant changes from baseline in vital signs

  Through study termination, an average of 36 weeks

• Part 3: Number of participants with clinically significant changes from baseline in physical examinations

  Through study termination, an average of 36 weeks

• Part 3: Number of participants with clinically significant changes in electrocardiogram (ECG)

  Through study termination, an average of 36 weeks

Secondary Outcomes (36)

• Part 1: Proportion of participants who are AAE-C1INH attack-free during Treatment Phase

  12 weeks

• Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during Treatment Phase

  12 weeks

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

  12 weeks

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

  12 weeks

• Part 1: Proportion of participants achieving ≥50%, ≥70% and ≥90% reduction in AAE-C1NH attack rate relative to baseline during Treatment Phase

  12 weeks

Study Arms (5)

Part 1 - Arm 1 - Active

EXPERIMENTAL

Drug: Deucrictibant

Part 1 - Arm 2 - Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part 2 - Arm 1

EXPERIMENTAL

Drug: Deucrictibant; Drug: Placebo

Part 2 - Arm 2

EXPERIMENTAL

Drug: Deucrictibant; Drug: Placebo

Part 3 - Open-label

EXPERIMENTAL

Drug: Deucrictibant

Interventions

Placebo DRUG

Part 1: Placebo Comparator tablet for once daily oral use

Part 1 - Arm 2 - Placebo

Deucrictibant DRUG

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

Part 1 - Arm 1 - Active

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pharvaris Netherlands B.V.: lead

Study Sites (32)

Study Site

San Diego, California, 92093, United States

RECRUITING

Study Site

Walnut Creek, California, 94598,, United States

RECRUITING

Study Site

St Louis, Missouri, 63130, United States

RECRUITING

Study Site

Hershey, Pennsylvania, 17033, 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

Study Site

Paris, France

RECRUITING

Study Site

Berlin, Germany

RECRUITING

Study Site

Frankfurt am Main, Germany

RECRUITING

Study Site

Munich, Germany

RECRUITING

Study Site

Budapest, Hungary

RECRUITING

Study Site 1

Milan, Italy

RECRUITING

Study Site 2

Milan, Italy

RECRUITING

Study Site 3

Milan, Italy

RECRUITING

Study Site

Padova, Italy

RECRUITING

Study Site

Roma, Italy

RECRUITING

Study Site

Amsterdam, Netherlands

RECRUITING

Study Site

Auckland, New Zealand

RECRUITING

Study Site

Krakow, Poland

RECRUITING

Study Site

Madrid, Spain

RECRUITING

Study Site

Basel, Switzerland

RECRUITING

Study Site

Ankara, Turkey (Türkiye)

RECRUITING

Study Site

Bristol, United Kingdom

RECRUITING

Study Site

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

MeSH Terms

Conditions

Angioedemas, Hereditary; Angioedema; Acquired angioedema

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Study Director, Pharvaris

  Pharvaris Netherlands B.V.

  STUDY DIRECTOR

Central Study Contacts

Pharvaris Clinical Team

CONTACT

0031-712-036-410; clinicaltrials@pharvaris.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 is parallel Part 2 is crossover Part 3 is single group

Study Record Dates

• First Submitted: October 20, 2025
• First Posted: December 5, 2025
• Study Start: October 16, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 21, 2026

Record last verified: 2026-09

Locations

US (4); TU (1); NZ (1); AU (1); ES (1); NL (1); PL (1); CA (1); GB (6); FR (3); CH (1); IT (5); DE (3); BU (1); HU (1)