A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II

Hereditary Angioedema Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04208412
• Other study ID #: KVD900-201
• Status: Completed
• Phase: Phase 2
• Start date: July 2, 2019
• Est. completion date: December 8, 2020

Study information

• Verified date: January 2023
• 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 II, cross-over clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adult subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: December 8, 2020
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema
• Hereditary Angioedema Types I and II

Intervention

Drug:
• KVD900
KVD900 tablet 600 mg

Other:
• Placebo
KVD900-matched Placebo Tablet

Locations

Country	Name	City	State
Austria	KalVista Investigative Site	Wien
Czechia	KalVista Investigative Site	Brno
Czechia	KalVista Investigative Site	Hradec Králové
Czechia	KalVista Investigative Site	Pilsen
Germany	KalVista Investigative Site	Berlin
Germany	KalVista Investigative Site	Frankfurt
Germany	KalVista Investigative Site	Morfelden-Walldorf
Hungary	KalVista Investigative Site	Budapest
Italy	KalVista Investigative Site	Milano
Italy	KalVista Investigative Site	Milano-2
Italy	KalVista Investigative Site	Padova
Netherlands	KalVista Investigative Site	Amsterdam
North Macedonia	KalVista Investigative Site	Skopje
Poland	KalVista Investigative Site	Kraków
Poland	KalVista Investigative Site	Warsaw
United Kingdom	KalVista Investigative Site	Camberley
United Kingdom	KalVista Investigative Site	Cambridge
United Kingdom	KalVista Investigative Site	London
United Kingdom	KalVista Investigative Site	Newcastle
United States	KalVista Investigative Site	Centennial	Colorado
United States	KalVista Investigative Site	Chevy Chase	Maryland
United States	KalVista Investigative Site	Cincinnati	Ohio
United States	KalVista Investigative Site	Dallas	Texas
United States	KalVista Investigative Site	Scottsdale	Arizona
United States	KalVista Investigative Site	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
KalVista Pharmaceuticals, Ltd.

Countries where clinical trial is conducted

United States,  Austria,  Czechia,  Germany,  Hungary,  Italy,  Netherlands,  North Macedonia,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)	The primary variable for statistical comparison between treatments in Part 2 of the study was time to use of conventional attack treatment (pdC1INH or rhC1INH intravenous [iv] or icatibant) within 12 hours of study drug.; Censoring occurs where a subject did not use conventional attack treatment within 12h post-study drug dosing.; When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred >12 hours following study drug.	12 hours
Secondary	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)	The proportion of participant's HAE attacks to either worsen in attack severity on the PGI-S by one level or more or conventional attack treatment (pdC1INH or rhC1INH intravenous [iv] or icatibant) use are listed with censored observations flagged. Frequencies (n, %) of subjects experiencing a worsening on the PGI-S by one level or more or using conventional attack treatment and the number censored are presented. "Y" Row indicates "participants who experienced a worsening in severity, and the "N" Row indicates participants who did not.	12 hours
Secondary	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)	HAE attack severity assessed using the Patient Global Impression of Severity scale (PGI-S).; Censoring occurs where a subject did not worsen in severity or use conventional attack treatment (pdC1INH or rhC1INH intravenous [iv] or icatibant) within 12h post-study drug dosing.; When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred >12 hours following study drug.	12 hours
Secondary	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)	Change in HAE attack severity assessed using the Patient Global Impression of Change 7-point transition question (PGI-C).; Censoring occurs where an attack rating of "a little better" or higher for two consecutive time points does not occur or conventional attack treatment is used within 12h post-study drug dosing.; When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred >12 hours following study drug.	12 hours
Secondary	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)	The HAE attack symptoms were assessed on a 100 mm visual analogue scale (VAS) ranging from 0 (none) to 100 (very severe).; The Composite VAS score is defined as the mean score across all symptoms. Censoring occurs where a =50% reduction in Composite VAS Score for three consecutive time points does not occur or conventional attack treatment is used within 12h post-study drug dosing.; When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur the event must have occurred >12 hours following study drug.	12 hours