We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05396105
Recruitment Status : Recruiting
First Posted : May 31, 2022
Last Update Posted : February 22, 2023
Sponsor:
Information provided by (Responsible Party):
Pharvaris Netherlands B.V.

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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)
Actual Study Start Date : December 28, 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: 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 Name: 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 Name: PHVS416


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Treatment-emergent Adverse Events (TEAEs), treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs [ Time Frame: From enrollment through study completion, up to 40 months (dependent on time of enrollment). ]
  2. Heart Rate [ Time Frame: 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.

  3. Blood pressure [ Time Frame: 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.

  4. Body temperature [ Time Frame: 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 :
  1. Time to onset of symptom relief (TOSR) assessed by the 3- or 5-symptom visual analog scale score (VAS-3 or VAS-5) [ Time Frame: 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.

  2. Time to almost complete or complete symptom relief (TACSR and TCSR) assessed by VAS-3 or VAS-5 [ Time Frame: 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.

  3. Time to symptom improvement based on patient global impression of severity (PGI-S) [ Time Frame: Assessed from pre-treatment to 48 hours post-treatment ]
    PGI-S evaluates the severity of attack symptoms with a 5-point response scale.

  4. Time to symptom improvement based on patient global impression of change (PGI-C) [ Time Frame: 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.

  5. Change of VAS-3 score and individual VAS score from pre-treatment to 4 h post-treatment for non-laryngeal attacks [ Time Frame: Pre-treatment and 4 hours post-treatment ]
    VAS-3 scores range between 0 and 100. A larger reduction means a better outcome.

  6. Change in Mean symptom complex severity (MSCS) score [ Time Frame: Assessed from pre-treatment to 48 hours post-treatment ]
    MSCS scores range between 0 and 3. A higher score means a worse outcome.

  7. Treatment outcome score (TOS) [ Time Frame: 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.

  8. Proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121 [ Time Frame: From enrollment through study completion, up to 40 months (dependent on time of enrollment). ]
  9. 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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (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. must have received at least 1 dose of study drug (including the non-attack visit) in Study PHA022121-C201.

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 enrolment
  5. History of alcohol or drug abuse within defined period, or current evidence of substance dependence or abuse
  6. Discontinued from Study PHA022121-C201 after enrollment for any study drug-related safety reason.
  7. 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).
  8. Participation in any other investigational drug study within defined period
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05396105


Contacts
Layout table for location contacts
Contact: Pharvaris Clinical Team +31 (71) 203-6410 clinicaltrials@pharvaris.com

Locations
Layout table for location information
United States, Alabama
Study site Active, not recruiting
Birmingham, Alabama, United States, 35209
United States, Arizona
Study site Active, not recruiting
Scottsdale, Arizona, United States, 85258
United States, California
Study site Active, not recruiting
Walnut Creek, California, United States, 94598
Bulgaria
Study site Recruiting
Sofia, Bulgaria
Czechia
Study site Recruiting
Brno, Czechia
France
Study site Recruiting
Grenoble, France, 38043
Study site Recruiting
La Tronche, France, 38700
Study site Recruiting
Paris, France, 75010
Germany
Study site Recruiting
Berlin, Germany, 10114
Study site Recruiting
Frankfurt am Main, Germany, 60596
Hungary
Study site Recruiting
Budapest, Hungary
Spain
Study site Recruiting
Barcelona, Spain, 08035
Study site Recruiting
Barcelona, Spain, 08907
Sponsors and Collaborators
Pharvaris Netherlands B.V.
Investigators
Layout table for investigator information
Principal Investigator: Marcus Maurer, Prof MD Charite University, Berlin, Germany
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Pharvaris Netherlands B.V.
ClinicalTrials.gov Identifier: NCT05396105    
Other Study ID Numbers: PHA022121-C303
First Posted: May 31, 2022    Key Record Dates
Last Update Posted: February 22, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
On-Demand
Additional relevant MeSH terms:
Layout table for 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
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes