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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05055258




Registration number
NCT05055258
Ethics application status
Date submitted
14/09/2021
Date registered
24/09/2021

Titles & IDs
Public title
A Trial to Evaluate the Efficacy and Safety of Different Doses of KVD824 for Prophylactic Treatment of HAE Type I or II
Scientific title
Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Efficacy and Safety of 3 Dose Levels of KVD824, an Oral Plasma Kallikrein Inhibitor, for Long-Term Prophylactic Treatment of Hereditary Angioedema Type I or II
Secondary ID [1] 0 0
KVD824-201
Universal Trial Number (UTN)
Trial acronym
KVD824-201
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Angioedema, Hereditary, Types I and II 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
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KVD824
Treatment: Drugs - Placebo to KVD824

Experimental: 300 mg KVD824 - 300 mg KVD824 twice a day for 12 weeks

Experimental: 600 mg KVD824 - Two 300 mg KVD824 tablets twice a day for 12 weeks

Experimental: 900 mg KVD824 - Three 300 mg KVD824 tablets twice a day for 12 weeks

Placebo comparator: Placebo to KVD824 - One, two or three placebo tablets to be taken twice a day for 12 weeks


Treatment: Drugs: KVD824
KVD824 300 mg Modified-Release Tablets

Treatment: Drugs: Placebo to KVD824
Placebo to KVD824 300 mg Modified-Release Tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Rate of Investigator-confirmed HAE attacks during the Treatment Period
Timepoint [1] 0 0
12 weeks
Secondary outcome [1] 0 0
Proportion of subjects without Investigator-confirmed HAE attacks during the Treatment Period.
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Rate of Investigator-confirmed HAE attacks that require conventional treatment during the Treatment Period.
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Angioedema Quality of Life Questionnaire (AE-QoL) total score and domain scores during the Treatment Period.
Timepoint [3] 0 0
12 weeks
Secondary outcome [4] 0 0
Angioedema Control Test (AECT) score and domain scores during the Treatment Period.
Timepoint [4] 0 0
12 weeks
Secondary outcome [5] 0 0
Proportion of subjects with an AECT score =12 at the end of the Treatment Period.
Timepoint [5] 0 0
12 weeks

Eligibility
Key inclusion criteria
1. Male or female subjects 18 years of age and older.
2. Confirmed diagnosis of HAE type I or II at any time in the medical history:

1. Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria) AND EITHER
2. Diagnostic testing results obtained prior to randomization that confirm HAE Type I or II: C1-INH functional level <40% of the normal level. Subjects with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. Testing may be obtained from central or local laboratories or obtained from documented historical testing results. Subjects may be restested at anytime prior to randomization if results are incongruent with clinical history or believed by the Investigator to be confounded by recent prophylactic or therapeutic C1 INH use, OR
3. Documented genetic results that confirm known mutations for HAE Type I or II.
3. Subject has access to and ability to use conventional treatment for HAE attacks.
4. Subject is willing to cease any current medications being taken for HAE prophylaxis and Investigator determines that doing so would not place the subject at any undue safety risk.
5. Subject's last dose of attenuated androgens was at least 28 days prior to first dose of IMP.
6. During the Run-in Period subject meets one of the following criteria:

1. Two Investigator-confirmed attacks in the first 4-week period.
2. Three Investigator-confirmed attacks in =8 weeks.
7. Subjects who are fertile and heterosexually active must adhere to contraception requirements throughout the trial as follows:

a) Female subjects must agree to use at least one highly effective contraception method from the Screening Visit until the end of the trial. Highly effective methods of contraception include: i) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral/injectable/implantable (hormonal contraception that contains estrogen including ethinylestradiol is excluded per
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion 4).

ii) Intrauterine device (IUD). iii) Intrauterine hormone-releasing system (IUS). iv) Bilateral tubal occlusion. v) Vasectomized partner (provided that the partner is the sole sexual partner of the female subject of childbearing potential and that the vasectomized partner has received medical assessment of surgical success).

b) Male subjects with a female partner of childbearing potential must agree to use condoms for the entire Treatment Period AND for 90 days following the final dose of investigational medicinal product (IMP). Female partners are encouraged to use contraception as outlined in Inclusion 7a) from the Screening Visit until the end of the trial. Hormonal contraception that contains estrogen including ethinylestradiol is acceptable for the female partner.
8. Subjects who are not fertile or not sexually active, as defined below, do not require contraception.

1. Subjects who refrain from heterosexual intercourse during the trial if the reliability of the heterosexual abstinence has been evaluated in relation to the duration of the clinical trial and is the preferred and usual lifestyle of the subject.
2. Male subjects who are surgically sterile (e.g. vasectomized with medical assessment of surgical success).
3. Female subjects who are surgically sterile (e.g. status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post menopausal for at least 12 months.
9. Subjects must be able to swallow trial tablets whole.
10. Subjects assessed by the Investigator must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.
11. Investigator believes that the subject is willing and able to adhere to all protocol requirements.
12. Subject provides signed informed consent and is willing and capable of complying with trial requirements and procedures.

Exclusion Criteria

1. 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.
2. A clinically significant history of poor response to C1-INH therapy or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator.
3. Use of angiotensin converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization.
4. Any estrogen containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) after the Screening Visit or within 7 days prior to randomization.
5. Use of narrow therapeutic index drugs metabolized by CYP3A4 or CYP2C9 or transported by OAT1, OCT2, and OATP1B1, starting at screening, as determined by the Investigator.
6. Use of strong CYP3A4 inhibitors and inducers during participation in the trial, starting at the Screening Visit.

Note: These medications include but are not limited to the following:

Inhibitors: boceprevir, clarithromycin, cobicistat, dasabuvir, denoprevir, elvitegravir, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir ombitasvir, paritaprevir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, and voriconazole.

Inducers: apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's Wort.
7. 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.
6. Estimated glomerular filtration rate (eGFR) <60 mL/min.
8. Any clinically significant comorbidity or systemic dysfunction that in the opinion of the Investigator would jeopardize the safety of the subject by participating in the trial.
9. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
10. Known hypersensitivity to KVD824 or placebo or to any of the excipients.
11. Any prior use of any gene therapy treatment for HAE.
12. Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to screening.
13. Any pregnant or breastfeeding subject.

Study design
Purpose of the study
Prevention
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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/10/2022
Sample size
Target
Accrual to date
Final
33
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
KalVista Investigative Site - Campbelltown
Recruitment postcode(s) [1] 0 0
- Campbelltown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Bulgaria
State/province [13] 0 0
Sofia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Czechia
State/province [15] 0 0
Brno
Country [16] 0 0
Czechia
State/province [16] 0 0
Praha
Country [17] 0 0
France
State/province [17] 0 0
Grenoble
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
Germany
State/province [19] 0 0
Rheinland-Pfalz
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
State/province [21] 0 0
Frankfurt am main
Country [22] 0 0
Hungary
State/province [22] 0 0
Budapest
Country [23] 0 0
Italy
State/province [23] 0 0
Milan
Country [24] 0 0
Italy
State/province [24] 0 0
Padova
Country [25] 0 0
New Zealand
State/province [25] 0 0
Auckland
Country [26] 0 0
North Macedonia
State/province [26] 0 0
Skopje
Country [27] 0 0
Puerto Rico
State/province [27] 0 0
San Juan
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Birmingham
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Leeds
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Newcastle Upon Tyne

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
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


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05055258