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

• Sponsor: Pharvaris Netherlands B.V. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04618211
• Collaborator: (none)
• Enrollment: 74
• Locations: 36
• Arms: 3
• Anticipated Duration (Months): 18.9
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

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
• Actual Enrollment: 74 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: Feb 3, 2021
• Anticipated Primary Completion Date: Sep 1, 2022
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: 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
Other: 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
Other: 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 [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 [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 from the pre-treatment value.

2. Proportion of study drug treated attacks requiring HAE rescue medication [Assessed at 4 hours post-study drug treatment]

   Qualifying attacks treated with study drug may use approved rescue medication if no symptom relief within 4 h has been experienced.

3. Time to onset of almost complete and complete symptom relief by visual analogue scale (VAS-3) [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 having a value < 10. Complete symptom relief is defined as all 3 individual VAS scores are of the VAS-3 having a value of 0.

4. Mean symptom complex severity (MSCS) score [4 hours post-treatment]

   MSCS scores range between 0 and 3. A higher score means a worse outcome.

5. Treatment outcome score (TOS) [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.

6. 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.

7. Treatment-emergent adverse events (TEAEs) [From post-dose non-attack visit through study completion, approximately 26 weeks]

8. Treatment-related adverse events (AEs) [From post-dose non-attack visit through study completion, approximately 26 weeks]

9. Treatment-emergent serious adverse events (TESAEs) [From post-dose non-attack visit through study completion, approximately 26 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 prior to screening

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

Locations

	Site	City	State	Country	Postal Code
1	Study site	Birmingham	Alabama	United States	35209
2	Study site	Paradise Valley	Arizona	United States	85253
3	Study site	San Diego	California	United States	92122
4	Study site	Santa Monica	California	United States	90404
5	Study site	Walnut Creek	California	United States	94598
6	Study site	Chevy Chase	Maryland	United States	20815
7	Study site	Saint Louis	Missouri	United States	63141
8	Study site	Hershey	Pennsylvania	United States	17033
9	Study site	Sofia		Bulgaria
10	Study site	Edmonton	Alberta	Canada
11	Study site	Ottawa	Ontario	Canada
12	Study site	Toronto	Ontario	Canada
13	Study site	Montréal	Quebec	Canada
14	Study site	Québec City	Quebec	Canada
15	Study site	Brno		Czechia
16	Study site	Hradec Králové		Czechia
17	Study site	Grenoble		France
18	Study site	Montpellier		France
19	Study site	Paris		France
20	Study site	Berlin		Germany
21	Study site	Dresden		Germany
22	Study site	Frankfurt		Germany
23	Study site	Mainz		Germany
24	Study site	Ulm		Germany
25	Study site	Budapest		Hungary
26	Study site	Ashkelon		Israel
27	Study site	Haifa		Israel
28	Study site	Tel Aviv		Israel
29	Study site	Monserrato		Italy
30	Study site	Naples		Italy
31	Study site	Amsterdam		Netherlands
32	Study site	Kraków		Poland
33	Study site	Barcelona		Spain
34	Study site	Madrid		Spain
35	Study site	Brighton		United Kingdom
36	Study site	London		United Kingdom

Sponsors and Collaborators

• Pharvaris Netherlands B.V.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pharvaris Netherlands B.V.
• ClinicalTrials.gov Identifier: NCT04618211
• Other Study ID Numbers: PHA022121-C201; 2020-003445-11
• First Posted: Nov 5, 2020
• Last Update Posted: Aug 24, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• 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

Study Results

No Results Posted as of Aug 24, 2022