Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (HAE CHAPTER-1)

• ClinicalTrials.gov Identifier: NCT05047185
• Recruitment Status: Active, not recruiting
• First Posted: September 17, 2021
• Last Update Posted: February 21, 2024
• Sponsor: Pharvaris Netherlands B.V.
• Information provided by (Responsible Party): Pharvaris Netherlands B.V.

Tracking Information

• First Submitted Date: September 7, 2021
• First Posted Date: September 17, 2021
• Last Update Posted Date: February 21, 2024
• Actual Study Start Date: April 19, 2022
• Actual Primary Completion Date: October 2, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 7, 2021): Number of investigator-confirmed HAE attacks [ Time Frame: Day 0 to Day 84 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 17, 2023)

• Number of investigator-confirmed moderate or severe HAE attacks during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number of patients achieving reduction in attack rate during the treatment period relative to baseline [ Time Frame: Day 0 to Day 84 ]
• Number of patients that are attack-free during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number and proportion of days with angioedema symptoms during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Time to first investigator-confirmed HAE attack in the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital [ Time Frame: Day 0 to Day 84 ]
• Number of investigator-confirmed angioedema attacks during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]
• Number of investigator-confirmed moderate or severe angioedema attacks during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]
• Number of investigator-confirmed angioedema attacks requiring acute treatment during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]
• Incidence of HAE attacks during the treatment period in Part 2 (attack rate trend over time). [ Time Frame: Day 84 to Day 938 ]
• Number and proportion of days with angioedema symptoms during the treatment period in Part 2. [ Time Frame: Day 84 to Day 938 ]

Original Secondary Outcome Measures (submitted: September 7, 2021)

• Number of investigator-confirmed moderate or severe HAE attacks during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number of investigator-confirmed HAE attacks requiring acute treatment during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number of patients achieving reduction in attack rate during the treatment period relative to baseline [ Time Frame: Day 0 to Day 84 ]
• Number of patients that are attack-free during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number and proportion of days with angioedema symptoms during the treatment period [ Time Frame: Day 0 to Day 84 ]
• Time to first investigator-confirmed HAE attack in the treatment period [ Time Frame: Day 0 to Day 84 ]
• Number of investigator-confirmed HAE attacks resulting in a visit to the emergency department or an admission to hospital [ Time Frame: Day 0 to Day 84 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II
• Official Title: A Phase II, Double-blind, Placebo-controlled, Randomized, Dose-ranging, Parallel Group Study to Evaluate the Safety and Efficacy of PHA-022121 Administered Orally for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-Inhibitor Deficiency (Type I or Type II)
• Brief Summary: This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• 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 Deficiency
• C1 Inhibitor Deficiency

Intervention

• Drug: Deucrictibant low dose
  Deucrictibant softgel capsules for oral use (PHVS416)
• Drug: Deucrictibant high dose
  Deucrictibant softgel capsules for oral use (PHVS416)
• Drug: Placebo
  Matching placebo capsules for oral use

Study Arms

• Experimental: Part 1: Low dose
  BID low dose of deucrictibant
  Intervention: Drug: Deucrictibant low dose
• Experimental: Part 1: High dose
  BID high dose of deucrictibant
  Intervention: Drug: Deucrictibant high dose
• Placebo Comparator: Part 1: Placebo
  BID placebo
  Intervention: Drug: Placebo
• Experimental: Part 2: Open-label
  BID high dose of deucrictibant
  Intervention: Drug: Deucrictibant high dose

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 25, 2023): 34
• Original Estimated Enrollment (submitted: September 7, 2021): 30
• Estimated Study Completion Date: December 2026
• Actual Primary Completion Date: October 2, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Signed and dated informed consent form
• Diagnosis of HAE type I or II
• Documented history of at least 3 HAE attacks within the last 3 consecutive months prior to screening, or a minimum of 2 HAE attacks during the screening period
• Reliable access and experience to use standard of care acute attack medications

Exclusion Criteria:

• Pregnancy or breast-feeding
• Clinically significant abnormal electrocardiogram
• Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
• Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrolment
• Abnormal hepatic function
• Abnormal renal function
• History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
• Participation in any other investigational drug study within defined period

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Bulgaria, Canada, Germany, Ireland, Italy, Poland, United Kingdom, United States
• Removed Location Countries: Israel, Spain

Administrative Information

• NCT Number: NCT05047185
• Other Study ID Numbers: PHA022121-C301; 2021-000227-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Pharvaris Netherlands B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pharvaris Netherlands B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Marc Riedl, MD; UC San Diego, La Jolla, California, United States
• Principal Investigator: Emel Aygören-Pürsün, MD; University Hospital Frankfurt - Goethe University, Frankfurt, Germany

• PRS Account: Pharvaris Netherlands B.V.
• Verification Date: February 2024