Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients with Hereditary Angioedema

Phase 2

• 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
• Interventions: Drug: deucrictibant selected dose

• Registration Number: NCT05396105
• Lead Sponsor: Pharvaris Netherlands B.V.

Brief Summary

This study evaluates the safety and efficacy of long-term on-demand treatment with orally administered deucrictibant for acute hereditary angioedema (HAE) attacks, including laryngeal attacks, in participants with HAE type 1 or type 2 (HAE-1/2). The study will enroll patients from Study PHA022121-C201 (NCT04618211) and Study PHA022121-C306 (NCT06343779) who elect to participate in this extension study and meet the eligibility requirements.

Detailed Description

Part A of the study will enroll adult participants from Study PHA022121-C201. The double-blind treatment assignment from Study PHA022121-C201 will be maintained.

Part B will include participants rolling over from Part A and additionally enroll participants from Study PHA022121-C201 who did not participate in Part A, and participants from Study PHA022121-C306 who elect to participate in this extension study and meet the eligibility requirements.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Study Timeline

• Study First Submitted: 2022-04-28
• Study First Submitted QC: 2022-05-24
• Study First Posted: 2022-05-31
• Study Start: 2022-12-28
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-30
• Last Update Posted: 2024-10-02
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

1. Signed and dated informed consent form
2. Diagnosis of HAE type I or II
3. For participants from Study C201, received at least one dose of study drug (including the non-attack visit) in Study C201. For participants from Study C306, participant was randomized (and for adolescent participants 12 to <18 years received a dose of study drug in a non-attack state at Visit 1) and completed Study C306, with 2 attacks treated, or after closure of that study by the Sponsor.
4. In the opinion of the Investigator, the participant (and parent/caregiver for adolescent participants) is willing and able to comply with the protocol.

Key

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Exclusion Criteria

1. Pregnancy or breast-feeding

2. Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study

3. Use of lanadelumab for long-term HAE prophylactic therapy within 12 weeks prior to enrollment in Part A.

4. For Part A: Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrolment.

   For Part B: If a participant is receiving long-term prophylactic therapy with one of the following medications indicated for HAE: plasma-derived C1-INH, danazol at less than or equal to 200 mg/day, anti-fibrinolytics, berotralstat, or lanadelumab, they must be on a stable dose and regimen for at least 3 months before screening and intends to remain on the same dose for the duration of the study.

5. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse

6. Participation in any other investigational drug study within defined period

7. Discontinued from parent study after enrollment for any study drug-related safety reason.

8. Use of concomitant medications that are potent CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir, grapefruit) or potent CYP3A4 inducers (e.g., phenytoin, rifampicin, St. John's Wort).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part B: Selected dose	deucrictibant selected dose	Single dose of deucrictibant

Primary Outcome Measures

Name	Time	Method
Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), treatment-related TESAEs, and TEAEs leading to deucrictibant discontinuation	From enrollment through study completion, up to 54 months (dependent on time of enrollment).
Heart Rate	From enrollment through study completion, up to 54 months (dependent on time of enrollment).	Descriptive in nature, no formal statistical hypothesis testing will be performed.
Blood pressure	From enrollment through study completion, up to 54 months (dependent on time of enrollment).	Systolic and diastolic blood pressure will be measured. Descriptive in nature, no formal statistical hypothesis testing will be performed.
Body temperature	From enrollment through study completion, up to 54 months (dependent on time of enrollment).	Descriptive in nature, no formal statistical hypothesis testing will be performed.
Clinical laboratory tests	From enrollment through study completion, up to 54 months (dependent on time of enrollment).	hematology, blood chemistry, urinalysis
Electrocardiograms	From enrollment through study completion, up to 54 months (dependent on time of enrollment).

Secondary Outcome Measures

Name	Time	Method
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	Assessed from 1 hour to 12 hours post-treatment	PGI-C evaluates the change in the attack symptoms over time with a 7-point response scale.
Time to onset of symptom relief by VAS-3/VAS-5 (Part A) or AMRA (Part B), defined as a reduction of ≥30% from pretreatment in VAS/AMRA composite score, sustained for 2 consecutive timepoints)	Assessed from pre-treatment to 48 hours post-treatment	VAS scores range between 0 and 100. A larger reduction means a better outcome.
Time to symptom relief by VAS (Part A) or AMRA (Part B), based on achieving ≥50% reduction from pretreatment in VAS/AMRA composite score sustained for 2 consecutive timepoints.	Assessed from pre-treatment to 48 hours post-treatment	VAS/AMRA scores range between 0 and 100. A larger reduction means a better outcome.
Proportion of deucrictibant-treated attacks requiring rescue medication within 24 hours post-treatment	Assessed from pre-treatment to 24 hours post-treatment
Time to substantial symptom relief, defined as achieving PGI-C rating of at least "better" for 2 consecutive timepoints within 12 hours post-treatment	Assessed from 1 hour to 12 hours post-treatment	PGI-C evaluates the change in the attack symptoms over time with a 7-point response scale.
Time to substantial symptom relief by Patient Global Impression of Severity (PGI-S), defined as achieving ≥1 point reduction in PGI-S from pre-treatment for 2 consecutive timepoints within 12 hours post-treatment	Assessed from pre-treatment to 12 hours post-treatment	PGI-S evaluates the severity of attack symptoms with a 5-point response scale.
Proportion of deucrictibant-treated attacks with almost complete or complete symptom relief by VAS-3/ VAS-5/ AMRA through 24 hours post-treatment	Assessed from pre-treatment to 24 hours post-treatment	Almost complete or complete symptom relief is defined as all individual item scores in VAS/AMRA having a value ≤10 sustained for 2 consecutive timepoints.

Trial Locations

Locations (1)

Study site; 🇪🇸 Madrid, Spain