A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II

NCT ID: NCT04208412

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-02
• Study Completion Date: 2020-12-08

Brief Summary

This study is a randomized, double-blind, placebo-controlled, phase II, cross-over clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adult subjects.

Conditions

Hereditary Angioedema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1

Subjects received a single dose of 600 mg KVD900.

Group Type: EXPERIMENTAL

KVD900

Intervention Type: DRUG

KVD900 tablet 600 mg

Part 2 - Sequence 1: 600 mg KVD900, Then Placebo

Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack.

Group Type: EXPERIMENTAL

KVD900

Intervention Type: DRUG

KVD900 tablet 600 mg

Placebo

Intervention Type: OTHER

KVD900-matched Placebo Tablet

Part 2 - Sequence 2: Placebo, Then 600 mg KVD900

Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack.

Group Type: EXPERIMENTAL

KVD900

Intervention Type: DRUG

KVD900 tablet 600 mg

Placebo

Intervention Type: OTHER

KVD900-matched Placebo Tablet

Interventions

KVD900

KVD900 tablet 600 mg

Intervention Type: DRUG

Placebo

KVD900-matched Placebo Tablet

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Male or female adult subjects 18 years of age and older.
• Confirmed diagnosis of HAE type I or II at anytime in the medical history
• At least 3 documented HAE attacks in the past 93 days, as supported by medical history.
• Access to and ability to use conventional attack treatment for attacks of HAE
• Adequate organ functions
• Females of childbearing potential must agree to use highly effective birth control from the Screening visit until the end of the trial follow-up procedures.
• Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months, do not require contraception during the study
• Males with female partners of childbearing potential must agree to be abstinent or else use a highly effective method of birth control as defined in inclusion 6 from the Screening visit until the end of the trial follow-up procedures
• Provide signed informed consent and are willing and capable of complying with study requirements and procedures

Exclusion Criteria

• Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor (C1-INH) deficiency, HAE with normal C1-INH (also known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria
• Current use of C1INH, androgens, or tranexamic acid for HAE prophylaxis
• Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 93 days prior to initial study treatment.
• Use of androgens (e.g. stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) or antifibrinolytics within 30 days prior to initial study treatment.
• Use of lanadelumab within 10 weeks prior to initial study treatment.
• Use of strong CYP3A4/CYP2C9 inhibitors and inducers during participation in the trial
• Clinically significant abnormal ECG at Visit 1 and pre-dose at Visit 2. This includes, but is not limited to, a QT interval by Fredericia, QTcF > 470 msec (for women) or > 450 msec (for men), a PR > 220 msec or ventricular and/or atrial premature contractions that are more frequent than occasional and/or occur as couplets or higher in grouping
• Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular abnormality
• Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory, cardiovascular) or significant disease or disorder which, in the opinion of the Investigator, would jeopardize the safety of the subject by taking part in the trial
• History of substance abuse or dependence that would interfere with the completion of the study, as determined by the Investigator
• Known lactose allergy or intolerance
• Known hypersensitivity to KVD900 or placebo or to any of the excipients
• Participation in an interventional investigational clinical study within 93 days or within 5 half-lives of the last dosing of investigational drug (whichever is longer) prior to initial study treatment
• Any pregnant or breast-feeding subject

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

KalVista Pharmaceuticals, Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

KalVista Pharmaceuticals, Ltd.

Locations

KalVista Investigative Site

Scottsdale, Arizona, United States

KalVista Investigative Site

Centennial, Colorado, United States

KalVista Investigative Site

Chevy Chase, Maryland, United States

KalVista Investigative Site

Cincinnati, Ohio, United States

KalVista Investigative Site

Dallas, Texas, United States

KalVista Investigative Site

Spokane, Washington, United States

KalVista Investigative Site

Vienna, , Austria

KalVista Investigative Site

Brno, , Czechia

KalVista Investigative Site

Hradec Králové, , Czechia

KalVista Investigative Site

Pilsen, , Czechia

KalVista Investigative Site

Berlin, , Germany

KalVista Investigative Site

Frankfurt, , Germany

KalVista Investigative Site

Mörfelden-Walldorf, , Germany

KalVista Investigative Site

Budapest, , Hungary

KalVista Investigative Site

Milan, , Italy

KalVista Investigative Site

Milano-2, , Italy

KalVista Investigative Site

Padua, , Italy

KalVista Investigative Site

Amsterdam, , Netherlands

KalVista Investigative Site

Skopje, , North Macedonia

KalVista Investigative Site

Krakow, , Poland

KalVista Investigative Site

Warsaw, , Poland

KalVista Investigative Site

Camberley, , United Kingdom

KalVista Investigative Site

Cambridge, , United Kingdom

KalVista Investigative Site

London, , United Kingdom

KalVista Investigative Site

Newcastle, , United Kingdom

Countries

United States; Austria; Czechia; Germany; Hungary; Italy; Netherlands; North Macedonia; Poland; United Kingdom

References

Aygoren-Pursun E, Zanichelli A, Cohn DM, Cancian M, Hakl R, Kinaciyan T, Magerl M, Martinez-Saguer I, Stobiecki M, Farkas H, Kiani-Alikhan S, Grivcheva-Panovska V, Bernstein JA, Li HH, Longhurst HJ, Audhya PK, Smith MD, Yea CM, Maetzel A, Lee DK, Feener EP, Gower R, Lumry WR, Banerji A, Riedl MA, Maurer M. An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Lancet. 2023 Feb 11;401(10375):458-469. doi: 10.1016/S0140-6736(22)02406-0.

Reference Type: DERIVED

PMID: 36774155 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KVD900-201

Identifier Type: -

Identifier Source: org_study_id