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)

Sponsor

KalVista Pharmaceuticals, Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05259917

Collaborator

(none)

114

Enrollment

Locations

Arms

Anticipated Duration (Months)

7.6

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Hereditary Angioedema	Drug: Placebo Drug: KVD900 600 mg Drug: KVD900 300 mg	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official 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

Actual Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Oct 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo Placebo to KVD900 Tablet
Experimental: KVD900 600 mg	Drug: KVD900 600 mg KVD900 Tablet 600 mg (2 x 300 mg)
Experimental: KVD900 300 mg	Drug: KVD900 300 mg KVD900 Tablet 300 mg (1 x 300 mg)

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Drug: Placebo

Placebo to KVD900 Tablet

Experimental: KVD900 600 mg

Drug: KVD900 600 mg

KVD900 Tablet 600 mg (2 x 300 mg)

Experimental: KVD900 300 mg

Drug: KVD900 300 mg

KVD900 Tablet 300 mg (1 x 300 mg)

Outcome Measures

Primary Outcome Measures

Time to beginning of symptom relief Patient Global Impression of Change (PGI-C) [within 12 hours of the first investigational medicinal product (IMP) administration.]
Time to beginning of symptom relief defined as at least "a little better" (2 time points in a row)

Secondary Outcome Measures

Time to first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) [within 12 hours of the first IMP administration.]
Time to HAE attack resolution (PGI-S) [within 24 hours of the first IMP administration.]
Time to HAE attack resolution defined as "none"
Proportion of attacks with beginning of symptom relief (PGI-C) [within 4 hours and within 12 hours of the first IMP administration.]
Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row)
Time to at least "better" (PGI-C) [within 12 hours of the first IMP administration.]
Time to first incidence of decrease from baseline (PGI-S) [within 24 hours of the first IMP administration.]
Time to at least a 50% decrease from baseline (3 time points in a row) Composite Visual Analogue Scale (VAS) [within 12 hours and within 24 hours of the first IMP administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 and be willing to remain on a stable dose and regimen for the duration of the trial.
Patient's last dose of attenuated androgens was at least 28 days prior to randomization.
Patient:

has had at least 2 documented HAE attacks within 3 months; or
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.

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:

Alanine aminotransferase (ALT) >2x upper limit of normal (ULN)
Aspartate aminotransferase (AST) >2x ULN
Bilirubin direct >1.25x ULN
International normalized ratio (INR) >1.2
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	KalVista Investigative Site	Birmingham	Alabama	United States	35209
2	KalVista Investigative Site	Scottsdale	Arizona	United States	85251
3	KalVista Investigative Site	Little Rock	Arkansas	United States	72205
4	KalVista Investigative Site	Santa Monica	California	United States	90404
5	KalVista Investigative Site	Centennial	Colorado	United States	80112
6	KalVista Investigative Site	Colorado Springs	Colorado	United States	80907
7	KalVista Investigative Site	Tampa	Florida	United States	33613
8	KalVista Investigative Site	Louisville	Kentucky	United States	40215
9	KalVista Investigative Site	Plymouth	Minnesota	United States	55446
10	KalVista Investigative Site	Saint Louis	Missouri	United States	61414
11	KalVista Investigative Site	Toledo	Ohio	United States	43617
12	KalVista Investigative Site	Dallas	Texas	United States	75231
13	KalVista Investigative Site	Spokane	Washington	United States	99204
14	KalVista Investigative Site	Toronto	Ontario	Canada	M3B 3S6
15	KalVista Investigative Site	San Juan		Puerto Rico	00918

Sponsors and Collaborators

KalVista Pharmaceuticals, Ltd.

Investigators

Study Director: Study Director, KalVista Pharmaceuticals, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

KalVista Pharmaceuticals, Ltd.

ClinicalTrials.gov Identifier:

NCT05259917

Other Study ID Numbers:

KVD900-301

First Posted:

Mar 2, 2022

Last Update Posted:

Jun 21, 2022

Last Verified:

Jun 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by KalVista Pharmaceuticals, Ltd.

KONFIDENT

Additional relevant MeSH terms:

Angioedema

Angioedemas, Hereditary

Study Results

No Results Posted as of Jun 21, 2022