A Phase III, Crossover Trial Evaluating the Efficacy and 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:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3, Three-way Crossover Trial to Evaluate the Efficacy and Safety of Two Dose Levels 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: Completed

Administrative data

• NCT number: NCT05259917
• Other study ID #: KVD900-301
• Status: Completed
• Phase: Phase 3
• Start date: February 23, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: January 2024
• Source: KalVista Pharmaceuticals, Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized, double-blind, placebo-controlled, phase III, three-way crossover clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adolescent and adult Patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients 12 years of age and older.

• Confirmed diagnosis of HAE type I or II at any time in the medical history.

• Patient has access to and ability to use conventional on-demand treatment for HAE attacks.

• If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must be on a stable dose and regimen for at least 3 months prior to the Screening Visit (except for danazol, which requires a stable dose and regimen for 6 months prior to the Screening Visit). Patient must be willing to remain on a stable dose and regimen for the duration of the trial.

• Patient's last dose of attenuated androgens other than danazol was at least 28 days prior to randomization.

• Patient:

1. has had at least 2 documented HAE attacks within 3 months prior to screening or randomization; or

2. is a completer of the KVD824-201 trial within 3 months prior to randomization and meets all other entry criteria to enroll in KVD900-301

• Patients must meet the contraception requirements.

• Patients must be able to swallow trial tablets whole.

• Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the electronic diary (eDiary).

• Investigator believes that the patient is willing and able to adhere to all protocol requirements.

• 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:

• 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.

• 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.

• Use of angiotensin-converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization.

• Any estrogen containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Screening Visit.

• Patients who require sustained use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.

• Inadequate organ function, including but not limited to:

1. Alanine aminotransferase (ALT) >2x upper limit of 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

• 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.

• History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.

• Known hypersensitivity to KVD900 or placebo or to any of the excipients.

• Prior participation in trial KVD900-201.

• Participation in any gene therapy treatment or trial for HAE.

• Participation in any interventional investigational clinical trial (with the exception of KVD824-201), including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to screening.

• Any pregnant or breastfeeding patient.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• Placebo
Placebo to KVD900 Tablet
• KVD900 600 mg
KVD900 Tablet 600 mg (2 x 300 mg)
• KVD900 300 mg
KVD900 Tablet 300 mg (1 x 300 mg)

Locations

Country	Name	City	State
Australia	KalVista Investigative Site	Campbelltown	New South Wales
Bulgaria	KalVista Investigative Site	Sofia
Canada	KalVista Investigative Site	Toronto	Ontario
France	KalVista Investigative Site	Grenoble Cedex 9
France	KalVista Investigative Site	Lille
France	KalVista Investigative Site	Lille
France	KalVista Investigative Site	Paris
Germany	KalVista Investigative Site	Berlin
Germany	KalVista Investigative Site	Frankfurt	Hessen
Germany	KalVista Investigative Site	Mainz
Germany	KalVista Investigative Site	Mörfelden-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	San Donato Milanese
Japan	KalVista Investgative Site	Chiba-shi
Japan	KalVista Investigative Site	Gunma
Japan	KalVista Investigative Site	Hiroshima City
Japan	KalVista Investigative Site	Saitama
Japan	KalVista Investgative Site	Takatsuki-shi	Osaka
Japan	KalVista Investigative Site	Yokohama
Netherlands	KalVista Investigative Site	Amsterdam
New Zealand	KalVista Investigative Site	Auckland
North Macedonia	KalVista Investigative Site	Skopje
Poland	KalVista Investigative Site	Bialystok
Poland	KalVista Investigative Site	Kraków
Poland	KalVista Investigative Site	Lódz
Portugal	KalVista Investigative Site	Porto
Puerto Rico	KalVista Investigative Site	San Juan
Romania	KalVista Investigative Site	Sângeorgiu De Mures	Mures
Slovakia	KalVista Investigative Site	Martin
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	Cardiff
United Kingdom	KalVista Investigative Site	Frimley
United Kingdom	KalVista Investigative Site	Leeds
United Kingdom	KalVista Investigative Site	London
United States	KalVista Investigative Site	Birmingham	Alabama
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	Chicago	Illinois
United States	KalVista Investigative Site	Colorado Springs	Colorado
United States	KalVista Investigative Site	Dallas	Texas
United States	KalVista Investigative Site	Hershey	Pennsylvania
United States	KalVista Investigative Site	Layton	Utah
United States	KalVista Investigative Site	Little Rock	Arkansas
United States	KalVista Investigative Site	Louisville	Kentucky
United States	KalVista Investigative Site	New York	New York
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	Tampa	Florida
United States	KalVista Investigative Site	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
KalVista Pharmaceuticals, Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  New Zealand,  North Macedonia,  Poland,  Portugal,  Puerto Rico,  Romania,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to beginning of symptom relief 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 the first investigational medicinal product (IMP) administration.
Secondary	Time to first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) (2 time points in a row)		within 12 hours of the first IMP administration.
Secondary	Time to HAE attack resolution (PGI-S)	Time to HAE attack resolution defined as "none"	within 24 hours of the first IMP administration.
Secondary	Proportion of attacks with beginning of symptom relief (PGI-C)	Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row)	within 4 hours and within 12 hours of the first IMP administration.
Secondary	Time to at least "better" (2 time points in a row) (PGI-C)		within 12 hours of the first IMP administration.
Secondary	Time to first incidence of decrease from baseline (2 time points in a row) (PGI-S)		within 24 hours of the first IMP administration.
Secondary	Time to at least a 50% decrease from baseline (3 time points in a row) Composite Visual Analogue Scale (VAS)		within 12 hours and within 24 hours of the first IMP administration