Clinical trial NCT04208412: A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II
Official title: A Randomized, Double-blind, Placebo-controlled, Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900, an Oral Plasma Kallikrein Inhibitor, in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hereditary Angioedema
Keywords: Sebetralstat
Lead sponsor: KalVista Pharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2019-12-23
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: 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 II, cross-over clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adult subjects.


Eligibility criteria: Inclusion Criteria:

* Male or female adult subjects 18 years of age and older.
* Confirmed diagnosis of HAE type I or II at anytime in the medical history
* At least 3 documented HAE attacks in the past 93 days, as supported by medical history.
* Access to and ability to use conventional attack treatment for attacks of HAE
* Adequate organ functions
* Females of childbearing potential must agree to use highly effective birth control from the Screening visit until the end of the trial follow-up procedures.
* Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months, do not require contraception during the study
* Males with female partners of childbearing potential must agree to be abstinent or else use a highly effective method of birth control as defined in inclusion 6 from the Screening visit until the end of the trial follow-up procedures
* Provide signed informed consent and are willing and capable of complying with study requirements and procedures

Exclusion Criteria:

* Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor (C1-INH) deficiency, HAE with normal C1-INH (also known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria
* Current use of C1INH, androgens, or tranexamic acid for HAE prophylaxis
* Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 93 days prior to initial study treatment.
* Use of androgens (e.g. stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) or antifibrinolytics within 30 days prior to initial study treatment.
* Use of lanadelumab within 10 weeks prior to initial study treatment.
* Use of strong CYP3A4/CYP2C9 inhibitors and inducers during participation in the trial
* Clinically significant abnormal ECG at Visit 1 and pre-dose at Visit 2. This includes, but is not limited to, a QT interval by Fredericia, QTcF \> 470 msec (for women) or \> 450 msec (for men), a PR \> 220 msec or ventricular and/or atrial premature contractions that are more frequent than occasional and/or occur as couplets or higher in grouping
* Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular abnormality
* Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory, cardiovascular) or significant disease or disorder which, in the opinion of the Investigator, would jeopardize the safety of the subject by taking part in the trial
* History of substance abuse or dependence that would interfere with the completion of the study, as determined by the Investigator
* Known lactose allergy or intolerance
* Known hypersensitivity to KVD900 or placebo or to any of the excipients
* Participation in an interventional investigational clinical study within 93 days or within 5 half-lives of the last dosing of investigational drug (whichever is longer) prior to initial study treatment
* Any pregnant or breast-feeding subject

Primary outcomes:
measure: Time to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)
timeFrame: 12 hours
Secondary outcomes:
measure: Proportion of HAE Attacks That Worsen in Severity by One Level or More on the PGI-S or Require Conventional Attack Treatment Within 12 Hours of Study Drug (Full Analysis Set)
timeFrame: 12 hours
measure: Time to Either Worsening in HAE Attack Severity by One Level or More on the PGI-S or to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)
timeFrame: 12 hours
measure: Time to Symptom Relief Defined as HAE Attack Rated as "A Little Better" or Higher on the PGI-C for Two Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)
timeFrame: 12 hours
measure: Time to Symptom Relief Defined as 50% Reduction in Composite VAS Score for Three Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)
timeFrame: 12 hours
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: KalVista Investigative Site
state: Arizona
city: Centennial
country: United States
facility: KalVista Investigative Site
state: Colorado
city: Chevy Chase
country: United States
facility: KalVista Investigative Site
state: Maryland
city: Cincinnati
country: United States
facility: KalVista Investigative Site
state: Ohio
city: Dallas
country: United States
facility: KalVista Investigative Site
state: Texas
city: Spokane
country: United States
facility: KalVista Investigative Site
state: Washington
city: Wien
country: Austria
facility: KalVista Investigative Site
city: Brno
country: Czechia
facility: KalVista Investigative Site
city: Hradec Králové
country: Czechia
facility: KalVista Investigative Site
city: Pilsen
country: Czechia
facility: KalVista Investigative Site
city: Berlin
country: Germany
facility: KalVista Investigative Site
city: Frankfurt
country: Germany
facility: KalVista Investigative Site
city: Morfelden-Walldorf
country: Germany
facility: KalVista Investigative Site
city: Budapest
country: Hungary
facility: KalVista Investigative Site
city: Milano-2
country: Italy
facility: KalVista Investigative Site
city: Milano
country: Italy
facility: KalVista Investigative Site
city: Padova
country: Italy
facility: KalVista Investigative Site
city: Amsterdam
country: Netherlands
facility: KalVista Investigative Site
city: Skopje
country: North Macedonia
facility: KalVista Investigative Site
city: Kraków
country: Poland
facility: KalVista Investigative Site
city: Warsaw
country: Poland
facility: KalVista Investigative Site
city: Camberley
country: United Kingdom
facility: KalVista Investigative Site
city: Cambridge
country: United Kingdom
facility: KalVista Investigative Site
city: London
country: United Kingdom
facility: KalVista Investigative Site
city: Newcastle
country: United Kingdom
facility: KalVista Investigative Site
Study officials:
affiliation: KalVista Pharmaceuticals, Ltd.
name: Study Director
role: STUDY_DIRECTOR
References: