RAPIDe-2: Extension Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema

Sponsor

Pharvaris Netherlands B.V. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05396105

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study evaluates the safety and efficacy of long-term on-demand treatment with orally administered PHA-022121 for acute hereditary angioedema (HAE) attacks, including laryngeal attacks, in patients with HAE due to C1-esterase inhibitor (C1-INH) deficiency (type I/II). The study will enroll patients from Study PHA022121-C201 (NCT04618211) who elect to participate in this extension study and meet the eligibility requirements.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: PHA-022121 low dose Drug: PHA-022121 medium dose Drug: PHA-022121 high dose Drug: PHA-022121 selected dose	Phase 2/Phase 3

Detailed Description

In Part A of the study, the double-blind treatment assignment from Study PHA022121-C201 will be maintained. The treatment in Part A will consist of 3 soft capsules per administered dose as in Study PHA022121-C201. In Part B of the study, the selected dose and formulation of PHA-022121 will be administered.

The to-be-marketed PHA-022121 formulation will be one single soft capsule at the strength proposed for marketing, based on the unblinding and evaluation of clinical data from Study PHA022121-C201. The duration of the treatment period (Part A plus Part B) is dependent upon the time of patient enrollment. The study is planned to continue until the availability of commercial supply, or another means of continued treatment can be provided.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase II/III, Extension Study of Orally Administered PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-Inhibitor Deficiency (Type I or Type II)

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Low dose Single low dose of PHA-022121 soft capsules for oral use (PHVS416)	Drug: PHA-022121 low dose PHA-022121 soft capsules for oral use (PHVS416) Other Names: PHVS416
Experimental: Part A: Medium dose Single medium dose of PHA-022121 soft capsules for oral use (PHVS416)	Drug: PHA-022121 medium dose PHA-022121 soft capsules for oral use (PHVS416) Other Names: PHVS416
Experimental: Part A: High dose Single high dose of PHA-022121 soft capsules for oral use (PHVS416)	Drug: PHA-022121 high dose PHA-022121 soft capsules for oral use (PHVS416) Other Names: PHVS416
Experimental: Part B: Selected dose Single dose of PHA-022121 soft capsules for oral use (PHVS416)	Drug: PHA-022121 selected dose PHA-022121 soft capsule for oral use (PHVS416) Other Names: PHVS416

Outcome Measures

Primary Outcome Measures

Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs [From enrollment through study completion, up to 40 months (dependent on time of enrollment).]
Heart Rate [From enrollment through study completion, up to 40 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 40 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 40 months (dependent on time of enrollment).]
Descriptive in nature, no formal statistical hypothesis testing will be performed.

Secondary Outcome Measures

Time to onset of symptom relief (TOSR) assessed by the 3- or 5-symptom visual analog scale score (VAS-3 or VAS-5) [Assessed from pre-treatment to 48 hours post-treatment]
VAS-3 (non-laryngeal attacks) and VAS-5 (laryngeal attacks) scores range between 0 and 100. Symptom relief is defined as a 50% or higher reduction of the VAS-3 or VAS-5 score from the pre-treatment value.
Time to almost complete or complete symptom relief (TACSR and TCSR) assessed by VAS-3 or VAS-5 [Assessed from pre-treatment to 48 hours post-treatment]
VAS scores range between 0 and 100. Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 or VAS-5 having a value < 10. Complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 or VAS-5 having a value of 0.
Time to symptom improvement based on patient global impression of severity (PGI-S) [Assessed from pre-treatment to 48 hours post-treatment]
PGI-S evaluates the severity of attack symptoms with a 5-point response scale.
Time to symptom improvement based on patient global impression of change (PGI-C) [Assessed from pre-treatment to 48 hours post-treatment]
PGI-C evaluates the change in the attack symptoms over time with a 7-point response scale.
Change of VAS-3 score and individual VAS score from pre-treatment to 4 h post-treatment for non-laryngeal attacks [Pre-treatment and 4 hours post-treatment]
VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.
Change in Mean symptom complex severity (MSCS) score [Assessed from pre-treatment to 48 hours post-treatment]
MSCS scores range between 0 and 3. A higher score means a worse outcome.
Treatment outcome score (TOS) [Assessed from pre-treatment to 4 hours post-treatment]
TOS scores range between -100 and 100. A positive score indicates improvement, a score of 0 indicates no change, and a negative score indicates worsening compared to pre-treatment.
Proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121 [From enrollment through study completion, up to 40 months (dependent on time of enrollment).]
Treatment satisfaction questionnaire for medication (TSQM) scores [48 hours post-treatment]
TSQM scores range from 0 to 100. A higher score means a better outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Signed and dated informed consent form
Diagnosis of HAE type I or II
must have received at least 1 dose of study drug (including the non-attack visit) in Study PHA022121-C201.

Key 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
History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
Discontinued from Study PHA022121-C201 after enrollment for any study drug-related safety reason.
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).
Participation in any other investigational drug study within defined period