Clinical trial NCT06669754: Study of Oral Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With HAE
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Keywords: HAE
Oral Treatment
Bradykinin B2 Receptor Antagonists
PHVS719
PHA121
Deucrictibant
Prophylaxis
Lead sponsor: Pharvaris Netherlands B.V.
Sponsor class: INDUSTRY
First posted: 2024-11-01
Enrollment: 81
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of once-daily orally administered deucrictibant extended-release tablet compared to placebo for prophylaxis to prevent angioedema attacks in participants aged ≥ 12 years with hereditary angioedema.

Detailed description: The study consists of a Screening Period during which eligibility is confirmed, a Treatment Period of 24 weeks, and a Follow-up Period of maximum 4 weeks or subjects may roll over into the open-label study PHA022121-C307 (CHAPTER-4). During the Treatment period participants will receive blinded study drug (deucrictibant or placebo randomized in a 2:1 ratio). Participants will undergo regular efficacy and safety assessments, complete an electronic diary daily, and also complete questionnaires at predefined timepoints during the study.

Eligibility criteria: Inclusion Criteria:

1. Provision of written informed consent/assent.
2. Male or female, aged ≥12 years at the time of providing written informed consent/assent.
3. Diagnosis of hereditary angioedema (HAE)
4. History of at least 3 HAE attacks within the 3 consecutive months prior to Screening Visit
5. Predefined number of attacks during the Screening Period
6. Reliable access and ability to use standard of care on-demand treatments to effectively manage acute HAE attacks.
7. Willing and able to adhere to all protocol requirements, including eDiary and ePRO data recording.
8. Female participants of childbearing potential must agree to the protocol specified pregnancy testing and contraception methods.

Exclusion Criteria:

1. Any diagnosis of angioedema other than HAE
2. 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 Screening (whichever is longer)
3. Has received prior prophylactic treatment with deucrictibant
4. Exposure to ACE inhibitors or any estrogen-containing medications with systemic absorption within 4 weeks of Screening
5. Prior gene therapy for any indication at any time
6. Use of prophylactic treatment for HAE within 2 weeks of Screening for C1INH, oral kallikrein inhibitors, or anti-fibrinolytics; within 4 weeks of Screening for attenuated androgens; within 5 half-lives of Screening for monoclonal antibodies, or within 7 days of Screening for short-term prophylaxis
7. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
8. Abnormal hepatic function
9. Moderate or severe renal impairment
10. Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
11. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse
12. Use of medications that are moderate and strong inhibitors or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) of the time of randomization
13. Known hypersensitivity to deucrictibant or any of the excipients of the study drug

Primary outcomes:
measure: Time-normalized (per 4 weeks) number of Investigator-confirmed HAE attacks during the 24-week Treatment Period
timeFrame: 24 weeks
Secondary outcomes:
measure: Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Time-normalized number of Investigator-confirmed severe HAE attacks during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Proportion of participants achieving ≥50% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Proportion of participants achieving ≥70% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Proportion of participants achieving ≥90% reduction in HAE attack rate relative to baseline during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Proportion of participants that are HAE attack-free during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Proportion of time without angioedema symptoms during the 24-week Treatment Period
timeFrame: 24 weeks
measure: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
timeFrame: Up to 38 weeks
measure: Pharmacokinetics [PK]: Deucrictibant plasma concentration time profiles
timeFrame: 24 weeks
measure: Patient reported outcome: Angioedema Quality of Life (AE-QoL) questionnaire
timeFrame: 24 weeks
measure: Patient reported outcome: Patient Global Assessment of Change (PGA-Change)
timeFrame: 24 weeks
measure: Patient reported outcome: Angioedema Control Test 4-week version (AECT-4wk)
timeFrame: 24 weeks
measure: Patient reported outcome: Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)
timeFrame: Up to 34 weeks
measure: Patient reported outcome: Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)
timeFrame: Up to 34 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Study Site
state: Arkansas
city: Santa Monica
country: United States
facility: Study site
state: California
city: Walnut Creek
country: United States
facility: Study site
state: California
city: Wheaton
country: United States
facility: Study Site
state: Maryland
city: Saint Louis
country: United States
facility: Study Site
state: Missouri
city: Corrientes
country: Argentina
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site
city: Sofia
country: Bulgaria
facility: Study Site
city: Edmonton
country: Canada
facility: Study Site
city: Ottawa
country: Canada
facility: Study Site
city: Grenoble
country: France
facility: Study Site
city: Brandenburg
country: Germany
facility: Study Site
city: Hongkong
country: Hong Kong
facility: Study Site
city: Dublin
country: Ireland
facility: Study Site
city: Veneto
country: Italy
facility: Study Site
city: Tokyo
country: Japan
facility: Study Site
city: Tokyo
country: Japan
facility: Study Site
city: Seoul
country: Korea, Republic of
facility: Study Site
city: Seoul
country: Korea, Republic of
facility: Study Site
city: Suwon
country: Korea, Republic of
facility: Study Site
city: Auckland
country: New Zealand
facility: Study Site
city: Kraków
country: Poland
facility: Study Site
city: San Juan
country: Puerto Rico
facility: Study Site
city: Sangeorgiu de Mures
country: Romania
facility: Study Site
city: Singapore
country: Singapore
facility: Study Site
city: Martin
country: Slovakia
facility: Study Site
city: Barcelona
country: Spain
facility: Study Site
city: Seville
country: Spain
facility: Study Site
city: Ankara
country: Turkey
facility: Study Site
city: İzmir
country: Turkey
facility: Study Site
city: London
country: United Kingdom
facility: Study site
state: England
city: Birmingham
country: United Kingdom
facility: Study Site
city: Birmingham
country: United Kingdom
facility: Study Site
city: Bristol
country: United Kingdom
facility: Study Site
city: Cambridge
country: United Kingdom
facility: Study Site
city: Frimley
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: