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

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ClinicalTrials.gov Identifier: NCT04618211
Recruitment Status : Recruiting
First Posted : November 5, 2020
Last Update Posted : December 10, 2021
Sponsor:
Information provided by (Responsible Party):
Pharvaris Netherlands B.V.

Tracking Information
First Submitted Date  ICMJE October 26, 2020
First Posted Date  ICMJE November 5, 2020
Last Update Posted Date December 10, 2021
Actual Study Start Date  ICMJE February 3, 2021
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2021)
  • 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 from the pre-treatment value.
  • Proportion of study drug treated attacks requiring HAE rescue medication [ Time Frame: 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.
  • Time to onset of almost complete and complete symptom relief by visual analogue scale (VAS-3) [ 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 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.
  • 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.
  • 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.
  • 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.
  • Treatment-emergent adverse events (TEAEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
  • Treatment-related adverse events (AEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
  • Treatment-emergent serious adverse events (TESAEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Occurrence of treatment-emergent adverse events (TEAEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
  • Occurrence of treatment-related adverse events (AEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
  • Occurrence of treatment-emergent serious adverse events (TESAEs) [ Time Frame: From post-dose non-attack visit through study completion, approximately 26 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-ranging Study of Oral PHA-022121 for Acute Treatment of Angioedema Attacks in Patients With Hereditary Angioedema
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: PHA-022121
    PHA-022121 soft capsules for oral use (PHVS416)
  • Drug: Placebo
    Matching placebo capsules for oral use
Study Arms  ICMJE
  • Low dose/placebo
    Single low dose of PHA-022121 or placebo
    Interventions:
    • Drug: PHA-022121
    • Drug: Placebo
  • Medium dose/placebo
    Single medium dose of PHA-022121 or placebo
    Interventions:
    • Drug: PHA-022121
    • Drug: Placebo
  • High dose/placebo
    Single high dose of PHA-022121 or placebo
    Interventions:
    • Drug: PHA-022121
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 9, 2021)
72
Original Estimated Enrollment  ICMJE
 (submitted: November 4, 2020)
54
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pharvaris Clinical Team +31 (71) 203-6410 clinicaltrials@pharvaris.com
Listed Location Countries  ICMJE Bulgaria,   Canada,   Czechia,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04618211
Other Study ID Numbers  ICMJE PHA022121-C201
2020-003445-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Pharvaris Netherlands B.V.
Study Sponsor  ICMJE Pharvaris Netherlands B.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marcus Maurer, Prof MD Charite University, Berlin, Germany
PRS Account Pharvaris Netherlands B.V.
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP