Clinical trial NCT06343779: Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Cross-over Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Attacks in Adolescents and Adults With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hereditary Angioedema
Hereditary Angioedema Type I
Hereditary Angioedema Type II
Hereditary Angioedema Types I and II
Hereditary Angioedema Attack
Hereditary Angioedema With C1 Esterase Inhibitor Deficiency
Hereditary Angioedema - Type 1
Hereditary Angioedema - Type 2
C1 Esterase Inhibitor [C1-INH] Deficiency
C1 Esterase Inhibitor Deficiency
C1 Esterase Inhibitor, Deficiency of
C1 Inhibitor Deficiency
Hereditary Angioedema - Type 3
Hereditary Angioedema Type III
Keywords: HAE
HAE Type I
HAE Type II
Oral Treatment
Bradykinin B2 Receptor Antagonists
PHVS416
PHA121
On-Demand
Deucrictibant
Pharvaris
HAE Type III
Lead sponsor: Pharvaris Netherlands B.V.
Sponsor class: INDUSTRY
First posted: 2024-04-03
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-period, 2-treatment cross-over study to evaluate the efficacy and safety of orally administered deucrictibant compared to placebo for the on-demand treatment of HAE attacks, including non-severe laryngeal attacks, in participants ≥12 to ≤75 years of age with HAE type 1, type 2, or type 3, a proportion of whom are using long-term prophylactic medication for HAE.

Detailed description: The study consists of a Screening Phase during which eligibility is confirmed, a Treatment Phase in which participants will be randomized and receive double blinded study drug to treat 2 qualifying HAE attacks (i.e., 2 Treatment Periods within the Treatment Phase), and an End-of-Study Follow-up Phase after the second attack treated with study drug. In addition, for adolescent participants (age ≥12 to \<18 years), PK samples are collected after administration of deucrictibant at Day 1 in a non-attack state.

Eligibility criteria: Inclusion Criteria:

1. Provision of written informed consent/assent.
2. Male or female, aged ≥12 to ≤75 years at the time of providing written informed consent/assent.
3. Diagnosis of HAE-1/2/3.
4. History of at least 2 HAE attacks in the last 3 months before screening.
5. Experience with using standard-of-care treatment to effectively manage on-demand treatment for HAE attacks.
6. Participants on long-term prophylactic therapy with plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat, or lanadelumab) must be on a stable dose and regimen and intend to remain on the same dose for 6 months before screening and the duration of the study. OR, Participant has stopped using plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat) at least 2 weeks or lanadelumab at least 10 weeks before screening.
7. Capable of recording, without assistance, electronic HAE diary and ePRO data using an electronic device.
8. For adolescent participants aged ≥12 and \<18 years of age: body weight ≥40 kg.
9. Female participants of childbearing potential must agree to the protocol specified pregnancy testing and contraception methods.

Exclusion Criteria:

1. Any female who is pregnant, plans to become pregnant, or is breastfeeding.
2. Any diagnosis of angioedema other than HAE.
3. Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
4. Use of attenuated androgens for short-term prophylaxis within 2 weeks before screening.
5. Abnormal hepatic function.
6. Abnormal renal function (eGFR \<60 ml/min/1.73 m2).
7. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
8. Has received prior on-demand HAE treatment with deucrictibant.
9. Currently participating in any other investigational drug study or receiving other investigational treatment within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
10. Prior gene therapy for any indication at any time.
11. Use of concomitant medications with systemic absorption that are strong inhibitors of CYP3A4 or strong inducers of CYP3A4 within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
12. Known hypersensitivity to study drug or any of the excipients of study drug.

Primary outcomes:
measure: Time to onset of symptom relief, defined as Patient Global Impression of Change (PGI-C) rating of at least "a little better" for 2 consecutive timepoints within 12 hours post-treatment.
timeFrame: Pre-treatment to 12 hours post-treatment.
Secondary outcomes:
measure: Proportion of study drug-treated attacks achieving PGI-C rating of at least "a little better" at 4 hours post-treatment.
timeFrame: Pre-treatment to 4 hours post-treatment.
measure: Time to substantial symptom relief, defined as achieving PGI-C rating of at least "better" for 2 consecutive timepoints within 12 hours post-treatment.
timeFrame: Pre-treatment to 12 hours post-treatment.
measure: Time to substantial symptom relief by Patient Global Impression of Severity (PGI-S).
timeFrame: Pre-treatment to 12 hours post-treatment.
measure: Time to complete symptom resolution, defined as achieving PGI-S rating of "none" within 48 hours post-treatment.
timeFrame: Pre-treatment to 48 hours post-treatment.
measure: Time to End of Progression (EoP) in attack symptoms within 12 hours.
timeFrame: Pre-treatment to 12 hours post-treatment.
measure: Proportion of study drug-treated attacks requiring rescue medication within 24 hours post-treatment.
timeFrame: Pre-treatment to 24 hours post-treatment.
measure: Proportion of attacks achieving symptom resolution.
timeFrame: Pre-treatment to 24 hours post-treatment.
measure: Time to substantial symptom relief by Angioedema Symptom Rating Scale (AMRA).
timeFrame: Pre-treatment to 12 hours post-treatment.
measure: Time to almost complete or complete symptom relief by AMRA.
timeFrame: Pre-treatment to 24 hours post-treatment.
measure: Proportion of study drug-treated attacks reaching almost complete or complete symptom relief by AMRA.
timeFrame: Pre-treatment to 24 hours post-treatment.
measure: Time to EoP in attack symptoms within 12 hours.
timeFrame: Pre-treatment to 12 hours post-treatment.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study Site
state: Alabama
city: Paradise Valley
country: United States
facility: Study Site
state: Arizona
city: Little Rock
country: United States
facility: Study Site
state: Arkansas
city: San Diego
country: United States
facility: Study Site
state: California
city: Santa Monica
country: United States
facility: Study Site
state: California
city: Walnut Creek
country: United States
facility: Study Site
state: California
city: Colorado Springs
country: United States
facility: Study Site
state: Colorado
city: Chevy Chase
country: United States
facility: Study Site
state: Maryland
city: Boston
country: United States
facility: Study Site
state: Massachusetts
city: Detroit
country: United States
facility: Study Site
state: Michigan
city: Saint Louis
country: United States
facility: Study Site
state: Missouri
city: Hershey
country: United States
facility: Study Site
state: Pennsylvania
city: Dallas
country: United States
facility: Study Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Study Site
city: Salta
country: Argentina
facility: Study Site
city: Campbelltown
country: Australia
facility: Study Site
state: New South Wales
city: Box Hill
country: Australia
facility: Study Site
city: Graz
country: Austria
facility: Study Site
city: Linz
country: Austria
facility: Study Site
city: Wien
country: Austria
facility: Study Site
city: Paraná
country: Brazil
facility: Study Site
city: Ribeirão Preto
country: Brazil
facility: Study Site
city: Salvador
country: Brazil
facility: Study Site
city: Santo André
country: Brazil
facility: Study Site
city: São Paulo
country: Brazil
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site
city: Edmonton
country: Canada
facility: Study Site
state: Alberta
city: Bogotá
country: Colombia
facility: Study Site
city: Bogotá
country: Colombia
facility: Study Site
city: Bogotá
country: Colombia
facility: Study Site
city: Medellín
country: Colombia
facility: Study Site
city: Brno
country: Czechia
facility: Study Site
city: Lille
country: France
facility: Study Site
city: Paris
country: France
facility: Study Site
city: Berlin
country: Germany
facility: Study Site
city: Frankfurt am Main
country: Germany
facility: Study Site
city: Frankfurt am Main
country: Germany
facility: Study Site
city: Lubeck
country: Germany
facility: Study Site
city: Hong Kong
country: Hong Kong
facility: Study Site
city: Budapest
country: Hungary
facility: Study Site
city: Dublin
country: Ireland
facility: Study Site
city: Catania
country: Italy
facility: Study Site
city: Milano
country: Italy
facility: Study Site
city: Milan
country: Italy
facility: Study Site
city: Padova
country: Italy
facility: Study Site
city: Palermo
country: Italy
facility: Study Site
city: Roma
country: Italy
facility: Study Site
city: Chiba-city
country: Japan
facility: Study Site
city: Hiroshima
country: Japan
facility: Study Site
city: Kanagawa
country: Japan
facility: Study Site
city: Osaka
country: Japan
facility: Study Site
city: Tokyo
country: Japan
facility: Study Site
city: Daegu
country: Korea, Republic of
facility: Study Site
city: Seoul
country: Korea, Republic of
facility: Study Site
city: Amsterdam
country: Netherlands
facility: Study Site
city: Skopje
country: North Macedonia
facility: Study Site
city: Kraków
country: Poland
facility: Study Site
city: San Juan
country: Puerto Rico
facility: Study Site
city: San Juan
country: Puerto Rico
facility: Study Site
city: Sângeorgiu De Mureş
country: Romania
facility: Study Site
city: Riyadh
country: Saudi Arabia
facility: Study Site
city: Singapore
country: Singapore
facility: Study Site
city: Cape Town
country: South Africa
facility: Study Site
city: Barcelona
country: Spain
facility: Study Site
city: Barcelona
country: Spain
facility: Study Site
city: Lund
country: Sweden
facility: Study Site
city: Ankara
country: Turkey
facility: Study Site
city: Istanbul
country: Turkey
facility: Study Site
city: İzmir
country: Turkey
facility: Study Site
city: Bristol
country: United Kingdom
facility: Study Site
city: Camberley
country: United Kingdom
facility: Study Site
city: Cambridge
country: United Kingdom
facility: Study Site
city: Leeds
country: United Kingdom
facility: Study Site
city: London
country: United Kingdom
facility: Study Site
city: Plymouth
country: United Kingdom
facility: Study Site
Study officials:
affiliation: Pharvaris Netherlands B.V.
name: Study Director, Pharvaris
role: STUDY_DIRECTOR
References: