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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05259917




Registration number
NCT05259917
Ethics application status
Date submitted
4/02/2022
Date registered
2/03/2022
Date last updated
31/01/2024

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 HAE attack resolution (PGI-S)
Timepoint [2] 0 0
within 24 hours of the first IMP administration.
Secondary outcome [3] 0 0
Proportion of attacks with beginning of symptom relief (PGI-C)
Timepoint [3] 0 0
within 4 hours and within 12 hours of the first IMP administration.
Secondary outcome [4] 0 0
Time to at least "better" (2 time points in a row) (PGI-C)
Timepoint [4] 0 0
within 12 hours of the first IMP administration.
Secondary outcome [5] 0 0
Time to first incidence of decrease from baseline (2 time points in a row) (PGI-S)
Timepoint [5] 0 0
within 24 hours of the first IMP administration.
Secondary outcome [6] 0 0
Time to at least a 50% decrease from baseline (3 time points in a row) Composite Visual Analogue Scale (VAS)
Timepoint [6] 0 0
within 12 hours and 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
23/02/2022
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
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Kentucky
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United States of America
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Maryland
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United States of America
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Minnesota
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United States of America
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Missouri
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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Pennsylvania
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Texas
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United States of America
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Utah
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United States of America
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Washington
Country [20] 0 0
Bulgaria
State/province [20] 0 0
Sofia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
France
State/province [22] 0 0
Grenoble Cedex 9
Country [23] 0 0
France
State/province [23] 0 0
Lille
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
Germany
State/province [25] 0 0
Hessen
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Mainz
Country [28] 0 0
Germany
State/province [28] 0 0
Mörfelden-Walldorf
Country [29] 0 0
Greece
State/province [29] 0 0
Athens
Country [30] 0 0
Hungary
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Budapest
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Israel
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Haifa
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Israel
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Petach Tikvah
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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
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United Kingdom
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Leeds
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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
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT05259917
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