Clinical trial NCT05505916: An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
Official title: An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900, an Oral Plasma Kallikrein Inhibitor, for On-demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema Type I or II
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: KONFIDENT-S
Sebetralstat
Lead sponsor: KalVista Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-18
Enrollment: 145
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter extension trial to evaluate the long-term safety of KVD900 in patients who are 12 years or older with HAE type I or II.


Eligibility criteria: Patients may roll over from KVD900-301.

Inclusion Criteria:

1. Confirmed diagnosis of HAE type I or II at any time in the medical history
2. Patient has had at least 2 documented HAE attacks within 3 months prior to the Enrollment Visit.
3. If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must have been on a stable dose and regimen for at least 3 months prior to the Enrollment Visit (except for danazol, which requires a stable dose and regimen for at least 6 months prior to the Enrollment Visit).
4. Male or female patients 12 years of age and older.
5. Patients must meet the contraception requirements.
6. Patients must be able to swallow trial tablets whole.
7. Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.
8. Investigator believes that the patient is willing and able to adhere to all protocol requirements.
9. Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required.

Exclusion Criteria:

1. Discontinued from the KVD900-301 trial for reasons of noncompliance, withdrawal of consent, or safety.
2. Presence of any safety concerns that would preclude participation in the open-label trial as determined by the investigator.
3. Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor deficiency, HAE with normal C1-INH (previously known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria.
4. A clinically significant history of poor response to bradykinin receptor 2 (BR2) blocker, C1-INH therapy, or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator.
5. Use of attenuated androgens other than danazol (e.g., stanozolol, oxandrolone, methyltestosterone, testosterone), or anti-fibrinolytics (e.g., tranexamicacid) within 28 days prior to the Enrollment Visit.
6. Use of Angiotensin-converting enzyme (ACE) inhibitors within 7 days prior to the Enrollment Visit.
7. Any estrogen-containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Enrollment Visit.
8. Inadequate organ function, including but not limited to:

   1. Alanine aminotransferase (ALT) \>2x Upper Limit Normal (ULN)
   2. Aspartate aminotransferase (AST) \>2x ULN
   3. Bilirubin direct \>1.25x ULN
   4. International Normalized Ratio (INR) \>1.2
   5. Clinically significant hepatic impairment defined as a Child-Pugh B or C
9. Any clinically significant comorbidity or systemic dysfunction, which in the opinion of the Investigator, would jeopardize the safety of the patient by participating in the trial.
10. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
11. Known hypersensitivity to KVD900 or to any of the excipients.
12. Participation in any gene therapy treatment or trial for HAE.
13. Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to the Enrollment Visit.
14. Any pregnant or breastfeeding patient.

Primary outcomes:
measure: Frequencies and percentages of patients with AEs, AEs within 2 days of IMP administration, serious AE's and AEs causing premature discontinuation.
timeFrame: AEs will be recorded from the first dose of IMP in the KVD900-302 trial up to and including the end of study (EOS) visit, a maximum of 2 years for each patient.
measure: Number and percentage of patients with normal or abnormal laboratory results at each scheduled visit.
timeFrame: Throughout the duration of the trial.
measure: Number and percentage of patients with normal or abnormal vital sign results at each scheduled visit
timeFrame: Throughout the duration of the trial.
Secondary outcomes:
measure: Patient Global Impression of Change (PGI-C).
timeFrame: within 12 hours of initial dose of IMP administration.
measure: Patient Global Impression of Severity (PGI-S): time to first incidence of 2 time points in a row decrease from baseline
timeFrame: within 12 hours of initial dose of IMP administration.
measure: PGI-S: time to HAE attack resolution
timeFrame: within 24 hours of initial dose of IMP administration.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: KalVista Investigative Site
state: Arizona
city: Little Rock
country: United States
facility: KalVista Investigative Site
state: Arkansas
city: San Diego
country: United States
facility: KalVista Investigative Site
state: California
city: San Diego
country: United States
facility: KalVista Investigative Site
state: California
city: Santa Monica
country: United States
facility: KalVista Investigative Site
state: California
city: Centennial
country: United States
facility: KalVista Investigative Site
state: Colorado
city: Colorado Springs
country: United States
facility: KalVista Investigative Site
state: Colorado
city: Evansville
country: United States
facility: KalVista Investigative Site
state: Indiana
city: Overland Park
country: United States
facility: KalVista Investigative Site
state: Kansas
city: Louisville
country: United States
facility: KalVista Investigative Site
state: Kentucky
city: Chevy Chase
country: United States
facility: KalVista Investigative Site
state: Maryland
city: Plymouth
country: United States
facility: KalVista Investigative Site
state: Minnesota
city: Saint Louis
country: United States
facility: KalVista Investigative Site
state: Missouri
city: Charlotte
country: United States
facility: KalVista Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: KalVista Investigative Site
state: Ohio
city: Toledo
country: United States
facility: KalVista Investigative Site
state: Ohio
city: Hershey
country: United States
facility: KalVista Investigative Site
state: Pennsylvania
city: Dallas
country: United States
facility: KalVista Investigative Site
state: Texas
city: Layton
country: United States
facility: KalVista Investgative Site
state: Utah
city: Spokane
country: United States
facility: KalVista Investigative Site
state: Washington
city: Campbelltown
country: Australia
facility: KalVista Investigative Site
city: Wein
country: Austria
facility: KalVista Investigative Site
city: Sofia
country: Bulgaria
facility: KalVista Investigative Site
city: Montréal
country: Canada
facility: KalVista Investigative Site
city: Grenoble Cedex 9
country: France
facility: KalVista Investigative Site
city: Lille Cedex
country: France
facility: KalVista Investigative Site
city: Lille
country: France
facility: KalVista Investigative Site
city: Paris
country: France
facility: KalVista Investigative Site
city: Berlin
country: Germany
facility: KalVista Investigative Site
city: Frankfurt
country: Germany
facility: KalVista Investigative Site
city: Mainz
country: Germany
facility: KalVista Investigative Site
city: Morfelden-Walldorf
country: Germany
facility: KalVista Investigative Site
city: Athens
country: Greece
facility: KalVista Investigative Site
city: Athens
country: Greece
facility: KalVista Investigative Site
city: Budapest
country: Hungary
facility: KalVista Investigative Site
city: Haifa
country: Israel
facility: KalVista Investigative Site
city: Petach Tikvah
country: Israel
facility: KalVista Investigative Site
city: Ramat Gan
country: Israel
facility: KalVista Investigative Site
city: Tel Aviv
country: Israel
facility: KalVista Investigative Site
city: Padova
country: Italy
facility: KalVista Investigative Site
city: Palermo
country: Italy
facility: KalVista Investigative Site
city: Roma
country: Italy
facility: KalVista Investigative Site
city: San Donato Milanese
country: Italy
facility: KalVista Investigative Site
city: Sapporo-city
country: Japan
facility: KalVista Investigative Site
state: Hokkaido
city: Chiba-shi
country: Japan
facility: KalVista Investigative Site
city: Hiroshima-shi
country: Japan
facility: KalVista Investigative Site
city: Kawagoe-shi
country: Japan
facility: KalVista Investigative Site
city: Maebashi-city
country: Japan
facility: KalVista Investigative Site
city: Soka-shi
country: Japan
facility: KalVista Investigative Site
city: Takatsuki-shi
country: Japan
facility: KalVista Investigative Site
city: Tokyo
country: Japan
facility: KalVista Investgative Site
city: Yokohama-shi
country: Japan
facility: KalVista Investigative Site
city: Amsterdam
country: Netherlands
facility: KalVista Investigative Site
city: Auckland
country: New Zealand
facility: KalVista Investigative Site
city: Skopje
country: North Macedonia
facility: KalVista Investigative Site
city: Kraków
country: Poland
facility: KalVista Investigative Site
city: Łódź
country: Poland
facility: KalVista Investigative Site
city: Porto
country: Portugal
facility: KalVista Investigative Site
city: Sângeorgiu De Mureş
country: Romania
facility: KalVista Investigative Site
city: Riyadh
country: Saudi Arabia
facility: KalVista Investigative Site
city: Martin
country: Slovakia
facility: KalVista Investigative Site
city: Cape Town
country: South Africa
facility: Kalvista Investigative Site
city: Barcelona
country: Spain
facility: KalVista Investigative Site
city: Barcelona
country: Spain
facility: KalVista Investigative Site
city: Madrid
country: Spain
facility: KalVista Investigative Site
city: Birmingham
country: United Kingdom
facility: KalVista Investigative Site
city: Cambridge
country: United Kingdom
facility: KalVista Investigative Site
city: Cardiff
country: United Kingdom
facility: KalVista Investigative Site
city: Frimley
country: United Kingdom
facility: KalVista Investigative Site
city: Leeds
country: United Kingdom
facility: KalVista Investigative Site
city: London
country: United Kingdom
facility: KalVista Investigative Site
city: London
country: United Kingdom
facility: KalVista Investigative Site
Study officials:
affiliation: KalVista Pharmaceuticals, Ltd.
name: Study Director
role: STUDY_DIRECTOR
References: