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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05259917




Registration number
NCT05259917
Ethics application status
Date submitted
4/02/2022
Date registered
2/03/2022

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
KVD900-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hereditary Angioedema 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - KVD900 600 mg
Treatment: Drugs - KVD900 300 mg

Placebo comparator: Placebo -

Experimental: KVD900 600 mg -

Experimental: KVD900 300 mg -


Treatment: Drugs: Placebo
Placebo to KVD900 Tablet

Treatment: Drugs: KVD900 600 mg
KVD900 Tablet 600 mg (2 x 300 mg)

Treatment: Drugs: KVD900 300 mg
KVD900 Tablet 300 mg (1 x 300 mg)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)
Timepoint [1] 0 0
Within 12 hours of the first investigational medicinal product (IMP) administration.
Secondary outcome [1] 0 0
Time to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)
Timepoint [1] 0 0
Within 12 hours of the first IMP administration.
Secondary outcome [2] 0 0
Time to Complete HAE Attack Resolution (PGI-S)
Timepoint [2] 0 0
Within 24 hours of the first IMP administration.

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/02/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2023
Sample size
Target
Accrual to date
Final
136
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
KalVista Investigative Site - Campbelltown
Recruitment postcode(s) [1] 0 0
2560 - Campbelltown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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Arkansas
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United States of America
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California
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United States of America
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Colorado
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United States of America
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Florida
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Illinois
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Kansas
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United States of America
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Kentucky
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Maryland
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Minnesota
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Missouri
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New York
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North Carolina
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Ohio
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Pennsylvania
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Texas
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Utah
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United States of America
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Washington
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Bulgaria
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Sofia
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Canada
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Ontario
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France
State/province [22] 0 0
Grenoble Cedex 9
Country [23] 0 0
France
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Lille
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France
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Paris
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Germany
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Hessen
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Germany
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Berlin
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Germany
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Mainz
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Germany
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Mörfelden-Walldorf
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Greece
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Athens
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Hungary
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Budapest
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Israel
State/province [31] 0 0
Haifa
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Israel
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Petach Tikvah
Country [33] 0 0
Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Padova
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Italy
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San Donato Milanese
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Japan
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Osaka
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Japan
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Chiba-shi
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Japan
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Gunma
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Japan
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Hiroshima City
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Japan
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Saitama
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Japan
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Yokohama
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Netherlands
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Amsterdam
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New Zealand
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Auckland
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North Macedonia
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Skopje
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Poland
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Bialystok
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Poland
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Kraków
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Poland
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Lódz
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Portugal
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Porto
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Puerto Rico
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San Juan
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Romania
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Mures
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Slovakia
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Martin
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Spain
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Barcelona
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Spain
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Madrid
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United Kingdom
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Birmingham
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United Kingdom
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Cardiff
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United Kingdom
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Frimley
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Leeds
Country [59] 0 0
United Kingdom
State/province [59] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
KalVista Pharmaceuticals, Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
KalVista Pharmaceuticals, Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will not be shared until all global regulatory filings are complete


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT05259917