Clinical trial NCT05259917: A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: KONFIDENT
Sebetralstat
Lead sponsor: KalVista Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 136
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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


Eligibility criteria: 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.

Primary outcomes:
measure: Time to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)
timeFrame: Within 12 hours of the first investigational medicinal product (IMP) administration.
Secondary outcomes:
measure: Time to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)
timeFrame: Within 12 hours of the first IMP administration.
measure: Time to Complete HAE Attack Resolution (PGI-S)
timeFrame: Within 24 hours of the first IMP administration.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: KalVista Investigative Site
state: Alabama
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: Tampa
country: United States
facility: KalVista Investigative Site
state: Florida
city: Chicago
country: United States
facility: KalVista Investigative Site
state: Illinois
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: New York
country: United States
facility: KalVista Investigative Site
state: New York
city: Charlotte
country: United States
facility: KalVista Investigative Site
state: North Carolina
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 Investigative Site
state: Utah
city: Spokane
country: United States
facility: KalVista Investigative Site
state: Washington
city: Campbelltown
country: Australia
facility: KalVista Investigative Site
state: New South Wales
city: Sofia
country: Bulgaria
facility: KalVista Investigative Site
city: Toronto
country: Canada
facility: KalVista Investigative Site
state: Ontario
city: Grenoble Cedex 9
country: France
facility: KalVista Investigative Site
city: Lille
country: France
facility: KalVista Investigative Site
city: Lille
country: France
facility: KalVista Investigative Site
city: Paris
country: France
facility: KalVista Investigative Site
city: Frankfurt
country: Germany
facility: KalVista Investigative Site
state: Hessen
city: Berlin
country: Germany
facility: KalVista Investigative Site
city: Mainz
country: Germany
facility: KalVista Investigative Site
city: Mörfelden-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: San Donato Milanese
country: Italy
facility: KalVista Investigative Site
city: Takatsuki-shi
country: Japan
facility: KalVista Investgative Site
state: Osaka
city: Chiba-shi
country: Japan
facility: KalVista Investgative Site
city: Gunma
country: Japan
facility: KalVista Investigative Site
city: Hiroshima City
country: Japan
facility: KalVista Investigative Site
city: Saitama
country: Japan
facility: KalVista Investigative Site
city: Yokohama
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: Białystok
country: Poland
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: San Juan
country: Puerto Rico
facility: KalVista Investigative Site
city: Sângeorgiu De Mureş
country: Romania
facility: KalVista Investigative Site
state: Mureş
city: Martin
country: Slovakia
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: 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
Study officials:
affiliation: KalVista Pharmaceuticals, Ltd.
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Riedl MA, Farkas H, Aygoren-Pursun E, Psarros F, Soteres DF, Staevska M, Cancian M, Hagin D, Honda D, Melamed I, Savic S, Stobiecki M, Busse PJ, Dias de Castro E, Agmon-Levin N, Gower R, Kessel A, Kurowski M, Lleonart R, Grivcheva Panovska V, Wedner HJ, Audhya PK, Hao J, Iverson M, Smith MD, Yea CM, Lumry WR, Zanichelli A, Bernstein JA, Maurer M, Cohn DM; KONFIDENT Investigators. Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks. N Engl J Med. 2024 Jul 4;391(1):32-43. doi: 10.1056/NEJMoa2314192. Epub 2024 May 31.