Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema (RAPIDe-1)

• ClinicalTrials.gov Identifier: NCT04618211
• Recruitment Status: Recruiting
• First Posted: November 5, 2020
• Last Update Posted: February 9, 2021
• Sponsor: Pharvaris Netherlands B.V.
• Information provided by (Responsible Party): Pharvaris Netherlands B.V.

Study Description

Brief Summary:

This study evaluates the efficacy of orally administered PHA-022121 for the acute treatment of attacks in patients with hereditary angioedema (HAE). Eligible subjects are randomized to one of three single doses of PHA-022121 and placebo. The study will compare symptom relief (skin pain, skin swelling, abdominal pain) during HAE attacks and safety of each dose of PHA-022121 with placebo.

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 Deficiency; C1 Inhibitor Deficiency	Drug: PHA-022121; Drug: Placebo	Phase 2

Detailed Description:

In Part I of the study, patients in non-attack state receive the assigned active single dose of PHA-022121 at the study center to assess pharmacokinetics (the way the body absorbs, distributes, and gets rid of the drug) and safety. In Part II of the study, patients self-administer blinded study drug at home to treat three HAE attacks with PHA-022121 or placebo (cross-over).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Double-blind, Placebo-controlled, Randomized, Cross-over, Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema Due to C1-inhibitor Deficiency Type I and II
• Actual Study Start Date: February 3, 2021
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: September 2022

Arms and Interventions

Arm	Intervention/treatment
Low dose/placebo; Single low dose of PHA-022121 or placebo	Drug: PHA-022121; PHA-022121 soft capsules for oral use (PHVS416); Drug: Placebo; Matching placebo capsules for oral use
Medium dose/placebo; Single medium dose of PHA-022121 or placebo	Drug: PHA-022121; PHA-022121 soft capsules for oral use (PHVS416); Drug: Placebo; Matching placebo capsules for oral use
High dose/placebo; Single high dose of PHA-022121 or placebo	Drug: PHA-022121; PHA-022121 soft capsules for oral use (PHVS416); Drug: Placebo; Matching placebo capsules for oral use

Outcome Measures

Primary Outcome Measures :

1. Change of the 3-symptom composite visual analogue scale (VAS-3) score from pre-treatment to 4 hours post-treatment [ Time Frame: Pre-treatment and 4 hours post-treatment ]
   VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

Secondary Outcome Measures :

1. Time to onset of symptom relief by visual analogue scale (VAS-3) score [ Time Frame: Assessed from pre-treatment to 48 hours post-treatment ]
   VAS-3 scores range between 0 and 100. Symptom relief is defined as a 50% or higher reduction of the VAS-3 score.
2. Time to onset of primary symptom relief by visual analogue scale (VAS) [ Time Frame: Assessed from pre-treatment to 48 hours post-treatment ]
   VAS scores range between 0 and 100. Primary symptom relief is defined as any VAS score reduction of the primary symptom above the threshold.
3. Mean symptom complex severity (MSCS) score [ Time Frame: 4 hours post-treatment ]
   MSCS scores range between 0 and 3. A higher score means a worse outcome.
4. Treatment outcome score (TOS) [ Time Frame: Pre-treatment and 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.
5. Treatment satisfaction questionnaire for medication (TSQM) scores [ Time Frame: 48 hours post-treatment ]
   TSQM scores range from 0 to 100. A higher score means a better outcome.
6. Occurrence of treatment-emergent adverse events (TEAEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
7. Occurrence of treatment-related adverse events (AEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
8. Occurrence of treatment-emergent serious adverse events (TESAEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Signed and dated informed consent form
2. Diagnosis of HAE type I or II
3. Documented history of HAE attacks: at least three in the last 4 months, or at least two in the last 2 months
4. Reliable access and experience to use standard of care acute attack medications

Key Exclusion Criteria:

1. Pregnancy or breast-feeding
2. Clinically significant abnormal electrocardiogram
3. Any other systemic disease or significant disease or disorder that would interfere with the patient's safety or ability to participate in the study
4. Use of C1-esterase inhibitor, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy within a defined period prior to enrollment
5. Positive serology for HIV or active infection with hepatitis B virus or hepatitis C virus
6. Abnormal hepatic function
7. Abnormal renal function
8. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
9. History of documented severe hypersensitivity to any medicinal product
10. Participation in any other investigational drug study within defined period

Contacts and Locations

Contacts

Contact: Clinical Team Pharvaris; +31 (71) 203-6410; clinical@pharvaris.com

Locations

Canada, Alberta

Study site; Not yet recruiting

Edmonton, Alberta, Canada

Canada, Ontario

Study site; Recruiting

Ottawa, Ontario, Canada

Study site; Recruiting

Toronto, Ontario, Canada

Canada, Quebec

Study site; Not yet recruiting

Montréal, Quebec, Canada

Study site; Not yet recruiting

Québec City, Quebec, Canada

Sponsors and Collaborators

Pharvaris Netherlands B.V.

Investigators

• Principal Investigator: Marcus Maurer, Prof MD; Charite University, Berlin, Germany

More Information

• Responsible Party: Pharvaris Netherlands B.V.
• ClinicalTrials.gov Identifier: NCT04618211
• Other Study ID Numbers: PHA022121-C201; 2020-003445-11 ( EudraCT Number )
• First Posted: November 5, 2020
• Last Update Posted: February 9, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Pharvaris Netherlands B.V.:

HAE; HAE Type I; HAE Type II; Oral Treatment; Bradykinin B2 Receptor Antagonists; PHVS416; PHA121

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Genetic Diseases, Inborn