An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)

NCT05505916 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: KVD900-302
• Study Type: interventional
• Target: 145
• Locations: 22 countries
• Sites: 70

Brief Summary

This is an open-label, multicenter extension trial to evaluate the long-term safety of KVD900 in patients who are 12 years or older with HAE type I or II.

Conditions

Hereditary Angioedema

Keywords

KONFIDENT-S; Sebetralstat

Outcome Measures

Primary Outcomes (3)

• Frequencies and percentages of patients with AEs, AEs within 2 days of IMP administration, serious AE's and AEs causing premature discontinuation.

  AEs will be recorded from the first dose of IMP in the KVD900-302 trial up to and including the end of study (EOS) visit, a maximum of 2 years for each patient.

• Number and percentage of patients with normal or abnormal laboratory results at each scheduled visit.

  Throughout the duration of the trial.

• Number and percentage of patients with normal or abnormal vital sign results at each scheduled visit

  Throughout the duration of the trial.

Secondary Outcomes (3)

• Patient Global Impression of Change (PGI-C).

  within 12 hours of initial dose of IMP administration.

• Patient Global Impression of Severity (PGI-S): time to first incidence of 2 time points in a row decrease from baseline

  within 12 hours of initial dose of IMP administration.

• PGI-S: time to HAE attack resolution

  within 24 hours of initial dose of IMP administration.

Study Arms (2)

KVD900 600 mg

EXPERIMENTAL

Drug: KVD900 600 mg

KVD900 300 mg

EXPERIMENTAL

Drug: KVD900 300 mg

Interventions

KVD900 600 mg DRUG

KVD900 Tablet 600 mg (2 x 300 mg)

KVD900 600 mg

KVD900 300 mg DRUG

KVD900 Tablet 300 mg

KVD900 300 mg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of HAE type I or II at any time in the medical history
• Patient has had at least 2 documented HAE attacks within 3 months prior to the Enrollment Visit.
• If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must have been on a stable dose and regimen for at least 3 months prior to the Enrollment Visit (except for danazol, which requires a stable dose and regimen for at least 6 months prior to the Enrollment Visit).
• Male or female patients 12 years of age and older.
• 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 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.

You may not qualify if:

• Discontinued from the KVD900-301 trial for reasons of noncompliance, withdrawal of consent, or safety.
• Presence of any safety concerns that would preclude participation in the open-label trial as determined by the investigator.
• 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 attenuated androgens other than danazol (e.g., stanozolol, oxandrolone, methyltestosterone, testosterone), or anti-fibrinolytics (e.g., tranexamicacid) within 28 days prior to the Enrollment Visit.
• Use of Angiotensin-converting enzyme (ACE) inhibitors within 7 days prior to the Enrollment Visit.
• Any estrogen-containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Enrollment Visit.
• Inadequate organ function, including but not limited to:
• Alanine aminotransferase (ALT) \>2x Upper Limit 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.

Sponsors & Collaborators

• KalVista Pharmaceuticals, Ltd.: lead

Study Sites (71)

KalVista Investigative Site

Scottsdale, Arizona, 85251, United States

Location

KalVista Investigative Site

Little Rock, Arkansas, 72205, United States

Location

KalVista Investigative Site

San Diego, California, 92122, United States

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KalVista Investigative Site

San Diego, California, 92123, United States

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KalVista Investigative Site

Santa Monica, California, 90404, United States

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KalVista Investigative Site

Centennial, Colorado, 80112, United States

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KalVista Investigative Site

Colorado Springs, Colorado, 80907, United States

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KalVista Investigative Site

Evansville, Indiana, 47715, United States

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KalVista Investigative Site

Overland Park, Kansas, 66211, United States

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KalVista Investigative Site

Louisville, Kentucky, 40215, United States

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KalVista Investigative Site

Chevy Chase, Maryland, 20815, United States

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KalVista Investigative Site

Plymouth, Minnesota, 55446, United States

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KalVista Investigative Site

St Louis, Missouri, 63141, United States

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KalVista Investigative Site

Charlotte, North Carolina, 28277, United States

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KalVista Investigative Site

Cincinnati, Ohio, 45236, United States

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KalVista Investigative Site

Toledo, Ohio, 43617, United States

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KalVista Investigative Site

Hershey, Pennsylvania, 17033, United States

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KalVista Investigative Site

Dallas, Texas, 75231, United States

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KalVista Investgative Site

Layton, Utah, 84041, United States

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KalVista Investigative Site

Spokane, Washington, 99204, United States

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KalVista Investigative Site

Campbelltown, 2560, Australia

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KalVista Investigative Site

Wein, 1090, Austria

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KalVista Investigative Site

Sofia, 1431, Bulgaria

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KalVista Investigative Site

Montreal, H2W 1R7, Canada

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KalVista Investigative Site

Grenoble, 38043, France

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KalVista Investigative Site

Lille, 59037, France

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KalVista Investigative Site

Paris, 75012, France

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KalVista Investigative Site

Berlin, 12203, Germany

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KalVista Investigative Site

Frankfurt, 60590, Germany

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KalVista Investigative Site

Mainz, 55131, Germany

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KalVista Investigative Site

Mörfelden-Walldorf, 64546, Germany

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KalVista Investigative Site

Athens, 11521, Greece

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KalVista Investigative Site

Athens, 11527, Greece

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KalVista Investigative Site

Budapest, 1088, Hungary

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KalVista Investigative Site

Haifa, 31048, Israel

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KalVista Investigative Site

Petach Tikvah, 4920235, Israel

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KalVista Investigative Site

Ramat Gan, 52621, Israel

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KalVista Investigative Site

Tel Aviv, 64239, Israel

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KalVista Investigative Site

Padua, 35128, Italy

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KalVista Investigative Site

Palermo, 90146, Italy

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KalVista Investigative Site

Roma, 00133, Italy

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KalVista Investigative Site

San Donato Milanese, 20097, Italy

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KalVista Investigative Site

Sapporo, Hokkaido, 002-8072, Japan

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KalVista Investigative Site

Chiba, 260-8677, Japan

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KalVista Investigative Site

Hiroshima, 730-8518, Japan

Location

KalVista Investigative Site

Kawagoe-shi, 350-8550, Japan

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KalVista Investigative Site

Maebashi, 371-8511, Japan

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KalVista Investigative Site

Soka-shi, 340-0041, Japan

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KalVista Investigative Site

Takatsuki-shi, 569-8686, Japan

Location

KalVista Investgative Site

Tokyo, 142-8666, Japan

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KalVista Investigative Site

Yokohama, 236-0004, Japan

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KalVista Investigative Site

Amsterdam, 1105 AZ, Netherlands

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KalVista Investigative Site

Auckland, 1023, New Zealand

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KalVista Investigative Site

Skopje, 1000, North Macedonia

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KalVista Investigative Site

Krakow, 31-503, Poland

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KalVista Investigative Site

Lodz, 92-213, Poland

Location

KalVista Investigative Site

Porto, 4200-319, Portugal

Location

KalVista Investigative Site

Sângeorgiu de Mureş, 547530, Romania

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KalVista Investigative Site

Riyadh, 11211, Saudi Arabia

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KalVista Investigative Site

Martin, 036 59, Slovakia

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Kalvista Investigative Site

Cape Town, 7700, South Africa

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KalVista Investigative Site

Barcelona, 08035, Spain

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KalVista Investigative Site

Barcelona, 08907, Spain

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KalVista Investigative Site

Madrid, 28046, Spain

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KalVista Investigative Site

Birmingham, B9 5SS, United Kingdom

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KalVista Investigative Site

Cambridge, CB2 0QQ, United Kingdom

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KalVista Investigative Site

Cardiff, CF14 4XW, United Kingdom

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KalVista Investigative Site

Frimley, GU16 7UJ, United Kingdom

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KalVista Investigative Site

Leeds, LS9 7TF, United Kingdom

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KalVista Investigative Site

London, E1 2ES, United Kingdom

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KalVista Investigative Site

London, NW3 2QG, United Kingdom

Location

Related Publications (2)

• Bernstein JA, Aygoren-Pursun E, Cancian M, Cohn DM, Craig T, Grivcheva-Panovska V, Jordan A, Lumry WR, Martinez-Saguer I, Melamed I, Ohmura K, Peter J, Riedl MA, Soteres DF, Staubach P, Stobiecki M, Chuang YH, Smith MD, Yea CM, Audhya PK, Zanichelli A, Farkas H. Sebetralstat for On-Demand Treatment of Mucosal Hereditary Angioedema Attacks in KONFIDENT-S. Clin Transl Allergy. 2025 Nov;15(11):e70118. doi: 10.1002/clt2.70118.

  PMID: 41252457 DERIVED

• 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 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 Nov;13(11):3094-3103.e5. doi: 10.1016/j.jaip.2025.08.020. Epub 2025 Aug 29.

  PMID: 40886933 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

sebetralstat

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Study Director

  KalVista Pharmaceuticals, Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 18, 2022
• Study Start: October 24, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); PL (2); JP (9); GR (2); PT (1); BU (1); RO (1); ZA (1); SA (1); FR (3); DE (4); HU (1); IT (4); NZ (1); ES (3); AU (1); NO (1); GB (7); CA (1); SL (1); US (20); IL (4)