A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)

NCT ID: NCT05259917

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-22
• Study Completion Date: 2023-12-31

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

Conditions

Hereditary Angioedema

Study Design

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

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo to KVD900 Tablet

KVD900 600 mg

Group Type: EXPERIMENTAL

KVD900 600 mg

Intervention Type: DRUG

KVD900 Tablet 600 mg (2 x 300 mg)

KVD900 300 mg

Group Type: EXPERIMENTAL

KVD900 300 mg

Intervention Type: DRUG

KVD900 Tablet 300 mg (1 x 300 mg)

Interventions

Placebo

Placebo to KVD900 Tablet

Intervention Type: DRUG

KVD900 600 mg

KVD900 Tablet 600 mg (2 x 300 mg)

Intervention Type: DRUG

KVD900 300 mg

KVD900 Tablet 300 mg (1 x 300 mg)

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 12 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

Birmingham, Alabama, United States

KalVista Investigative Site

Scottsdale, Arizona, United States

KalVista Investigative Site

Little Rock, Arkansas, United States

KalVista Investigative Site

San Diego, California, United States

KalVista Investigative Site

San Diego, California, United States

KalVista Investigative Site

Santa Monica, California, United States

KalVista Investigative Site

Centennial, Colorado, United States

KalVista Investigative Site

Colorado Springs, Colorado, United States

KalVista Investigative Site

Tampa, Florida, United States

KalVista Investigative Site

Chicago, Illinois, United States

KalVista Investigative Site

Overland Park, Kansas, United States

KalVista Investigative Site

Louisville, Kentucky, United States

KalVista Investigative Site

Chevy Chase, Maryland, United States

KalVista Investigative Site

Plymouth, Minnesota, United States

KalVista Investigative Site

St Louis, Missouri, United States

KalVista Investigative Site

New York, New York, United States

KalVista Investigative Site

Charlotte, North Carolina, United States

KalVista Investigative Site

Toledo, Ohio, United States

KalVista Investigative Site

Hershey, Pennsylvania, United States

KalVista Investigative Site

Dallas, Texas, United States

KalVista Investigative Site

Layton, Utah, United States

KalVista Investigative Site

Spokane, Washington, United States

KalVista Investigative Site

Campbelltown, New South Wales, Australia

KalVista Investigative Site

Sofia, , Bulgaria

KalVista Investigative Site

Toronto, Ontario, Canada

KalVista Investigative Site

Grenoble, , France

KalVista Investigative Site

Lille, , France

KalVista Investigative Site

Lille, , France

KalVista Investigative Site

Paris, , France

KalVista Investigative Site

Frankfurt am Main, Hesse, Germany

KalVista Investigative Site

Berlin, , Germany

KalVista Investigative Site

Mainz, , Germany

KalVista Investigative Site

Mörfelden-Walldorf, , Germany

Kalvista Investigative Site

Athens, , Greece

KalVista Investigative Site

Athens, , Greece

KalVista Investigative Site

Budapest, , Hungary

KalVista Investigative Site

Haifa, , Israel

KalVista Investigative Site

Petach Tikvah, , Israel

KalVista Investigative Site

Ramat Gan, , Israel

KalVista Investigative Site

Tel Aviv, , Israel

KalVista Investigative Site

Padua, , Italy

KalVista Investigative Site

San Donato Milanese, , Italy

KalVista Investgative Site

Takatsuki-shi, Osaka, Japan

KalVista Investgative Site

Chiba, , Japan

KalVista Investigative Site

Gunma, , Japan

KalVista Investigative Site

Hiroshima, , Japan

KalVista Investigative Site

Saitama, , Japan

KalVista Investigative Site

Yokohama, , Japan

KalVista Investigative Site

Amsterdam, , Netherlands

KalVista Investigative Site

Auckland, , New Zealand

KalVista Investigative Site

Skopje, , North Macedonia

KalVista Investigative Site

Bialystok, , Poland

KalVista Investigative Site

Krakow, , Poland

KalVista Investigative Site

Lodz, , Poland

KalVista Investigative Site

Porto, , Portugal

KalVista Investigative Site

San Juan, , Puerto Rico

KalVista Investigative Site

Sângeorgiu de Mureş, Mureș County, Romania

KalVista Investigative Site

Martin, , Slovakia

KalVista Investigative Site

Barcelona, , Spain

KalVista Investigative Site

Barcelona, , Spain

KalVista Investigative Site

Madrid, , Spain

KalVista Investigative Site

Birmingham, , United Kingdom

KalVista Investigative Site

Cardiff, , United Kingdom

KalVista Investigative Site

Frimley, , United Kingdom

KalVista Investigative Site

Leeds, , United Kingdom

KalVista Investigative Site

London, , United Kingdom

Countries

United States; Australia; Bulgaria; Canada; France; Germany; Greece; Hungary; Israel; Italy; Japan; Netherlands; New Zealand; North Macedonia; Poland; Portugal; Puerto Rico; Romania; Slovakia; Spain; United Kingdom

References

Riedl MA, Farkas H, Aygoren-Pursun E, Psarros F, Soteres DF, Staevska M, Cancian M, Hagin D, Honda D, Melamed I, Savic S, Stobiecki M, Busse PJ, Dias de Castro E, Agmon-Levin N, Gower R, Kessel A, Kurowski M, Lleonart R, Grivcheva Panovska V, Wedner HJ, Audhya PK, Hao J, Iverson M, Smith MD, Yea CM, Lumry WR, Zanichelli A, Bernstein JA, Maurer M, Cohn DM; KONFIDENT Investigators. Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema Attacks. N Engl J Med. 2024 Jul 4;391(1):32-43. doi: 10.1056/NEJMoa2314192. Epub 2024 May 31.

Reference Type: BACKGROUND

PMID: 38819658 (View on PubMed)

Farkas H, Anderson J, Bouillet L, Caballero T, Cancian M, Craig T, Fukunaga A, Grivcheva-Panovska V, Guilarte M, Honda D, Kanarek H, Kiani-Alikhan S, Kinaciyan T, Leguevaques D, Longhurst HJ, Magerl M, Manning ME, Martinez-Saguer I, Melamed I, O'Connor ME, Peter J, Savic S, Soteres DF, Staevska M, Staubach-Renz P, Stobiecki M, Tachdjian R, Valerieva A, Yong PFK, Hao J, Iverson M, Smith MD, Yea CM, Audhya PK, Aygoren-Pursun E, Bernstein JA, Cohn DM, Lumry WR, Riedl MA, Zanichelli A, Maurer M. Long-term Safety and Effectiveness of Sebetralstat: Interim Analysis of KONFIDENT-S Open-label Extension. J Allergy Clin Immunol Pract. 2025 Aug 29:S2213-2198(25)00821-9. doi: 10.1016/j.jaip.2025.08.020. Online ahead of print.

Reference Type: DERIVED

PMID: 40886933 (View on PubMed)

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

KVD900-301

Identifier Type: -

Identifier Source: org_study_id