A study to evaluate if different doses of KVD900 are safe and effective in treating attacks in patients with Hereditary Angioedema.

• Register: EUCTR
• Last refreshed on: 30 May 2022
• Main ID: EUCTR2021-001226-21-ES
• Date of registration: 16/03/2022
• Prospective Registration: Yes
• Primary sponsor: KalVista Pharmaceuticals Ltd
• Public title: A study to evaluate if different doses of KVD900 are safe and effective in treating attacks in patients with Hereditary Angioedema.
• 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 - KONFIDENT
• Date of first enrolment: 26/05/2022
• Target sample size: 114
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-001226-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Bulgaria, Canada, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, New Zealand, North Macedonia, Poland, Romania, Spain, United Kingdom, United States

Contacts

• Name: KalVista Clinical
• Affiliation: KalVista Pharmaceuticals Ltd

• Name: KalVista Clinical
• Affiliation: KalVista Pharmaceuticals Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1) Male or female patients 12 years of age and older.
2) Confirmed diagnosis of HAE type I or II at any time in the medical history.
3) Patient has access to and ability to use conventional on-demand treatment for HAE attacks.
4) If a patient is receiving long-term prophylactic treatment with one of these medicines indicated for HAE: iv or sc plasma-derived C1-INH, and/or lanadelumab, they must have been on a stable dose and regimen for at least 3 months prior to the Screening Visit and be willing to remain on a stable dose and regimen for the duration of the trial.
5) Patient’s last dose of attenuated androgens was at least 28 days prior to randomization.
6) Patient has had at least 2 documented HAE attacks within 3 months prior to randomization.
7) Patients must meet the contraception requirements.
8) Patients must be able to swallow trial tablets whole.
9) 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).
10) Investigator believes that the patient is willing and able to adhere to all protocol requirements.
11) Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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 bradykinin receptor 2 (BR2) blocker, 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) within 7 days prior to the Screening Visit.
5) Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors and inducers during participation in the trial, starting within 5 half-lives of the Screening Visit.
6) Inadequate organ function, including but not limited to:
a) Alanine aminotransferase (ALT) >2x upper limit of normal (ULN)
b) Aspartate aminotransferase (AST) >2x ULN
c) Bilirubin direct >1.25x ULN
d) International normalized ratio (INR) >1.2
e) Clinically significant hepatic impairment defined as a Child-Pugh B or C
7) 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.
8) History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
9) Known hypersensitivity to KVD900 or placebo or to any of the excipients.
10) Prior participation in trial KVD900-201.
11) Participation in any gene therapy treatment or trial 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 patient.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Hereditary Angioedema Type I or II
MedDRA version: 21.0 Level: LLT Classification code 10080956 Term: Hereditary angioedema type I System Organ Class: 100000004850
MedDRA version: 24.0 Level: LLT Classification code 10080960 Term: Hereditary angioedema type II System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: KVD900 300 mg Film Coated Tablet
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: None
Current Sponsor code: KVD900
Other descriptive name: KVD900
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The PGI C: Time to beginning of symptom relief defined as at least "a little better" (2 timepoints in a row) within 12 hours of the first IMP administration.

Main Objective: To demonstrate the clinical efficacy of KVD900 compared with placebo for the on-demand treatment of HAE attacks.

Timepoint(s) of evaluation of this end point: Within 12 hours of the first IMP administration.

Secondary Objective: To investigate the safety and tolerability of KVD900.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Within 12 hours of the first IMP administration.
Within 24 hours of the first IMP administration. Within 4 hours and within 12 hours of the first IMP administration.
Within 12 hours of the first IMP administration.
Within 24 hours of the first IMP administration.
Within 12 hours and within 24 hours of the first IMP administration

Secondary end point(s): •PGI-S: Time to first incidence of decrease from baseline within 12 hours of the first IMP administration.
•PGI-S: Time to HAE attack resolution defined as “none” within 24 hours of the first IMP administration.
•PGI-C: Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row) within 4 hours and within 12 hours of the first IMP administration.
•PGI-C: Time to at least "better" within 12 hours of the first IMP administration.
•PGI-S: Time to first incidence of decrease from baseline within 24 hours of the first IMP administration.
•Composite VAS: Time to at least a 50% decrease from baseline (3 time points in a row) within 12 hours and within 24 hours of the first IMP
administration

Secondary ID(s)

KVD900-301

2021-001226-21-HU

Source(s) of Monetary Support

KalVista Pharmaceuticals Ltd

Ethics review

Status: Approved
Approval date: 24/05/2022
Contact: