Clinical trial NCT06679881: Long-Term, Open-label Study of Oral Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With HAE
Official title: A Long-term, Open-label Study to Evaluate the Safety and Efficacy 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: 2024-11-08
Enrollment: 130
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, long-term, open-label study to evaluate the safety and efficacy of once-daily orally administered deucrictibant extended-release tablet 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 (only for participants not rolling over within 28 days from a previous deucrictibant prophylactic study), a Treatment Period in which participants will receive open-label deucrictibant extended-release tablet once daily for approximately 130 weeks, followed by an End of Study visit after maximum 4 weeks. Participants will undergo regular safety (e.g. lab draws) and efficacy assessments, will 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. For participants that did not participate in a previous deucrictibant prophylactic study: history of at least 1 attack in the last 3 consecutive months prior to Screening
5. Reliable access and ability to use standard of care on-demand treatments to effectively manage acute HAE attacks.
6. Willing and able to adhere to all protocol requirements, including eDiary and ePRO data recording.
7. Female participants of childbearing 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 ICF signature (whichever is longer)
3. Prior gene therapy for any indication at any time
4. Participants who discontinued from previous studies with deucrictibant prophylactic and/or on-demand treatment due to safety reasons or compliance issues that, in the opinion of the Investigator, would interfere with the participant's safety or compliance to participate in the study
5. Exposure to ACE inhibitors or any estrogen-containing medications with systemic absorption within 4 weeks of Screening
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: Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
timeFrame: Up to 138 weeks
measure: Change in heart rate
timeFrame: Up to 138 weeks
measure: Change in blood pressure
timeFrame: Up to 138 weeks
measure: Change in body temperature
timeFrame: Up to 138 weeks
measure: Change in clinical laboratory tests from baseline
timeFrame: Up to 138 weeks
measure: Change in electrocardiograms (ECGs) from baseline
timeFrame: Up to 138 weeks
Secondary outcomes:
measure: Time-normalized number of Investigator-confirmed HAE attacks during the Treatment Period
timeFrame: 130 weeks
measure: Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the Treatment Period
timeFrame: 130 weeks
measure: Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during Treatment Period
timeFrame: 130 weeks
measure: Time-normalized number of Investigator-confirmed severe HAE attacks during the Treatment Period
timeFrame: 130 weeks
measure: Proportion of time without angioedema symptoms during the Treatment Period
timeFrame: 130 weeks
measure: Patient reported outcome: Angioedema Quality of Life (AE-QoL) questionnaire
timeFrame: 130 weeks
measure: Patient reported outcome: Patient Global Assessment of Change (PGA-Change)
timeFrame: 130 weeks
measure: Patient reported outcome: Angioedema Control Test 4-week version (AECT-4wk)
timeFrame: 130 weeks
measure: Patient reported outcome: Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP)
timeFrame: Up to 134 weeks
measure: Patient reported outcome: Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)
timeFrame: Up to 134 weeks
measure: Pharmacokinetics [PK]: Deucrictibant plasma concentration pre-dose (Ctrough)
timeFrame: 130 weeks
Other outcomes:
Locations:
city: Walnut Creek
country: United States
facility: Study Site
state: California
city: Saint Louis
country: United States
facility: Study Site
state: Missouri
city: Sofia
country: Bulgaria
facility: Study Site
city: Hong Kong
country: Hong Kong
facility: Study Site
city: Dublin
country: Ireland
facility: Study Site
city: Kraków
country: Poland
facility: Study Site
city: Brighton
country: United Kingdom
facility: Study Site
city: Bristol
country: United Kingdom
facility: Study Site
city: Cambridge
country: United Kingdom
facility: Study Site
city: London
country: United Kingdom
facility: Study Site
Study officials:
affiliation: Pharvaris Netherlands B.V.
name: Study Director, Pharvaris
role: STUDY_DIRECTOR
References: