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
Primary Purpose
Hereditary Angioedema
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KVD900
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Angioedema
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
Sites / Locations
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
- KalVista Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1
Part 2 - Sequence 1: 600 mg KVD900, Then Placebo
Part 2 - Sequence 2: Placebo, Then 600 mg KVD900
Arm Description
Subjects received a single dose of 600 mg KVD900.
Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack.
Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT04208412
First Posted
December 20, 2019
Last Updated
January 16, 2023
Sponsor
KalVista Pharmaceuticals, Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04208412
Brief Title
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
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
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
July 2, 2019 (Actual)
Primary Completion Date
December 8, 2020 (Actual)
Study Completion Date
December 8, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
KalVista Pharmaceuticals, Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
84 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1
Arm Type
Experimental
Arm Description
Subjects received a single dose of 600 mg KVD900.
Arm Title
Part 2 - Sequence 1: 600 mg KVD900, Then Placebo
Arm Type
Experimental
Arm Description
Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack.
Arm Title
Part 2 - Sequence 2: Placebo, Then 600 mg KVD900
Arm Type
Experimental
Arm Description
Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.
Intervention Type
Drug
Intervention Name(s)
KVD900
Intervention Description
KVD900 tablet 600 mg
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
KVD900-matched Placebo Tablet
Primary Outcome Measure Information:
Title
Time to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)
Description
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.
Time Frame
12 hours
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
12 hours
Title
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)
Description
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.
Time Frame
12 hours
Title
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)
Description
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.
Time Frame
12 hours
Title
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)
Description
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.
Time Frame
12 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
KalVista Pharmaceuticals, Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
KalVista Investigative Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
KalVista Investigative Site
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
KalVista Investigative Site
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
KalVista Investigative Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
KalVista Investigative Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
KalVista Investigative Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
KalVista Investigative Site
City
Wien
Country
Austria
Facility Name
KalVista Investigative Site
City
Brno
Country
Czechia
Facility Name
KalVista Investigative Site
City
Hradec Králové
Country
Czechia
Facility Name
KalVista Investigative Site
City
Pilsen
Country
Czechia
Facility Name
KalVista Investigative Site
City
Berlin
Country
Germany
Facility Name
KalVista Investigative Site
City
Frankfurt
Country
Germany
Facility Name
KalVista Investigative Site
City
Morfelden-Walldorf
Country
Germany
Facility Name
KalVista Investigative Site
City
Budapest
Country
Hungary
Facility Name
KalVista Investigative Site
City
Milano-2
Country
Italy
Facility Name
KalVista Investigative Site
City
Milano
ZIP/Postal Code
1
Country
Italy
Facility Name
KalVista Investigative Site
City
Padova
Country
Italy
Facility Name
KalVista Investigative Site
City
Amsterdam
Country
Netherlands
Facility Name
KalVista Investigative Site
City
Skopje
Country
North Macedonia
Facility Name
KalVista Investigative Site
City
Kraków
Country
Poland
Facility Name
KalVista Investigative Site
City
Warsaw
Country
Poland
Facility Name
KalVista Investigative Site
City
Camberley
Country
United Kingdom
Facility Name
KalVista Investigative Site
City
Cambridge
Country
United Kingdom
Facility Name
KalVista Investigative Site
City
London
Country
United Kingdom
Facility Name
KalVista Investigative Site
City
Newcastle
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
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