An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900 for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)

Hereditary Angioedema Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05505916
• Other study ID #: KVD900-302
• Status: Recruiting
• Phase: Phase 3
• Start date: October 24, 2022
• Est. completion date: January 30, 2026

Study information

• Verified date: March 2024
• Source: KalVista Pharmaceuticals, Ltd.
• Contact: KalVista Pharmaceuticals
• Phone: 1 (857) 999-0075
• Email: clinicalstudies[@]kalvista.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: January 30, 2026
• Est. primary completion date: January 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• KVD900 600 mg
KVD900 Tablet 600 mg (2 x 300 mg)

Locations

Country	Name	City	State
Australia	KalVista Investigative Site	Campbelltown
Austria	KalVista Investigative Site	Wein
Bulgaria	KalVista Investigative Site	Sofia
Canada	KalVista Investigative Site	Montréal
France	KalVista Investigative Site	Grenoble Cedex 9
France	KalVista Investigative Site	Lille
France	KalVista Investigative Site	Lille Cedex
France	KalVista Investigative Site	Paris
Germany	KalVista Investigative Site	Berlin
Germany	KalVista Investigative Site	Frankfurt
Germany	KalVista Investigative Site	Mainz
Germany	KalVista Investigative Site	Morfelden-Walldorf
Greece	KalVista Investigative Site	Athens
Greece	KalVista Investigative Site	Athens
Hungary	KalVista Investigative Site	Budapest
Israel	KalVista Investigative Site	Haifa
Israel	KalVista Investigative Site	Petach Tikvah
Israel	KalVista Investigative Site	Ramat Gan
Israel	KalVista Investigative Site	Tel Aviv
Italy	KalVista Investigative Site	Padova
Italy	KalVista Investigative Site	Palermo
Italy	KalVista Investigative Site	Roma
Italy	KalVista Investigative Site	San Donato Milanese
Japan	KalVista Investigative Site	Chiba-shi
Japan	KalVista Investigative Site	Hiroshima-shi
Japan	KalVista Investigative Site	Kawagoe-shi
Japan	KalVista Investigative Site	Maebashi-city
Japan	KalVista Investigative Site	Sapporo-city	Hokkaido
Japan	KalVista Investigative Site	Soka-shi
Japan	KalVista Investigative Site	Takatsuki-shi
Japan	KalVista Investgative Site	Tokyo
Japan	KalVista Investigative Site	Yokohama-shi
Netherlands	KalVista Investigative Site	Amsterdam
New Zealand	KalVista Investigative Site	Auckland
North Macedonia	KalVista Investigative Site	Skopje
Poland	KalVista Investigative Site	Kraków
Poland	KalVista Investigative Site	Lódz
Portugal	KalVista Investigative Site	Porto
Romania	KalVista Investigative Site	Sângeorgiu De Mures
Saudi Arabia	KalVista Investigative Site	Riyadh
Slovakia	KalVista Investigative Site	Martin
South Africa	Kalvista Investigative Site	Cape Town
Spain	KalVista Investigative Site	Barcelona
Spain	KalVista Investigative Site	Barcelona
Spain	KalVista Investigative Site	Madrid
United Kingdom	KalVista Investigative Site	Birmingham
United Kingdom	KalVista Investigative Site	Cambridge
United Kingdom	KalVista Investigative Site	Cardiff
United Kingdom	KalVista Investigative Site	Frimley
United Kingdom	KalVista Investigative Site	Leeds
United Kingdom	KalVista Investigative Site	London
United Kingdom	KalVista Investigative Site	London
United States	KalVista Investigative Site	Centennial	Colorado
United States	KalVista Investigative Site	Charlotte	North Carolina
United States	KalVista Investigative Site	Chevy Chase	Maryland
United States	KalVista Investigative Site	Cincinnati	Ohio
United States	KalVista Investigative Site	Colorado Springs	Colorado
United States	KalVista Investigative Site	Dallas	Texas
United States	KalVista Investigative Site	Evansville	Indiana
United States	KalVista Investigative Site	Hershey	Pennsylvania
United States	KalVista Investgative Site	Layton	Utah
United States	KalVista Investigative Site	Little Rock	Arkansas
United States	KalVista Investigative Site	Louisville	Kentucky
United States	KalVista Investigative Site	Overland Park	Kansas
United States	KalVista Investigative Site	Plymouth	Minnesota
United States	KalVista Investigative Site	Saint Louis	Missouri
United States	KalVista Investigative Site	San Diego	California
United States	KalVista Investigative Site	San Diego	California
United States	KalVista Investigative Site	Santa Monica	California
United States	KalVista Investigative Site	Scottsdale	Arizona
United States	KalVista Investigative Site	Spokane	Washington
United States	KalVista Investigative Site	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
KalVista Pharmaceuticals, Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Bulgaria,  Canada,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  New Zealand,  North Macedonia,  Poland,  Portugal,  Romania,  Saudi Arabia,  Slovakia,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequencies and percentages of patients with AEs, AEs within 2 days of IMP administration, serious AE's and AEs causing premature discontinuation.		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.
Primary	Number and percentage of patients with normal or abnormal laboratory results at each scheduled visit.		Throughout the duration of the trial.
Primary	Number and percentage of patients with normal or abnormal vital sign results at each scheduled visit		Throughout the duration of the trial.
Secondary	Patient Global Impression of Change (PGI-C).	time to beginning of symptom relief defined as at least '' a little better'' (2 time points in a row)	within 12 hours of initial dose of IMP administration.
Secondary	Patient Global Impression of Severity (PGI-S): time to first incidence of 2 time points in a row decrease from baseline		within 12 hours of initial dose of IMP administration.
Secondary	PGI-S: time to HAE attack resolution	PGI-S: time to HAE attack resolution, defines as ''none''	within 24 hours of initial dose of IMP administration.