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)

NCT05259917 | Completed Phase 3 Results FDA Drug

• 1 other identifier: KVD900-301
• Study Type: interventional
• Target: 136
• Locations: 21 countries
• Sites: 66

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

Keywords

KONFIDENT; Sebetralstat

Outcome Measures

Primary Outcomes (1)

• Time to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)

  The analysis of time to the beginning of symptom relief defined as at least "a little better" (2 time points in a row) on the PGI-C within 12 hours of the first IMP administration using the Gehan score transformation test for Full Analysis Set (FAS). Attacks were treated as right-censored at 12 hours if they did not achieve beginning of symptom relief defined by PGI-C as at least "a little better" (2 time points in a row) or received conventional attack treatment prior to time-to-event within 12 hours of the first IMP administration. When an endpoint result was non-evaluable (NE) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

  Within 12 hours of the first investigational medicinal product (IMP) administration.

Secondary Outcomes (2)

• Time to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)

  Within 12 hours of the first IMP administration.

• Time to Complete HAE Attack Resolution (PGI-S)

  Within 24 hours of the first IMP administration.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

KVD900 600 mg

EXPERIMENTAL

Drug: KVD900 600 mg

KVD900 300 mg

EXPERIMENTAL

Drug: KVD900 300 mg

Interventions

Placebo DRUG

Placebo to KVD900 Tablet

Placebo

KVD900 600 mg DRUG

KVD900 Tablet 600 mg (2 x 300 mg)

KVD900 600 mg

KVD900 300 mg DRUG

KVD900 Tablet 300 mg (1 x 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:

• 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:
• has had at least 2 documented HAE attacks within 3 months prior to screening or randomization; 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• KalVista Pharmaceuticals, Ltd.: lead

Study Sites (66)

KalVista Investigative Site

Birmingham, Alabama, 35209, United States

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KalVista Investigative Site

Scottsdale, Arizona, 85251, United States

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KalVista Investigative Site

Little Rock, Arkansas, 72205, United States

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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

Tampa, Florida, 33613, United States

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KalVista Investigative Site

Chicago, Illinois, 60612, 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, 61414, United States

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KalVista Investigative Site

New York, New York, 10029, United States

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KalVista Investigative Site

Charlotte, North Carolina, 28277, 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 Investigative Site

Layton, Utah, 84041, United States

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KalVista Investigative Site

Spokane, Washington, 99202, United States

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KalVista Investigative Site

Campbelltown, New South Wales, 2560, Australia

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KalVista Investigative Site

Sofia, 1431, Bulgaria

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KalVista Investigative Site

Toronto, Ontario, M3B 3S6, Canada

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KalVista Investigative Site

Grenoble, 38043, France

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KalVista Investigative Site

Lille, 59000, France

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KalVista Investigative Site

Lille, 59037, France

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KalVista Investigative Site

Paris, 75571, France

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KalVista Investigative Site

Frankfurt am Main, Hesse, 60590, Germany

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KalVista Investigative Site

Berlin, 12203, 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, 49202, 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

San Donato Milanese, 20097, Italy

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KalVista Investgative Site

Takatsuki-shi, Osaka, 569-8686, Japan

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KalVista Investgative Site

Chiba, 260-8677, Japan

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KalVista Investigative Site

Gunma, 371-8511, Japan

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KalVista Investigative Site

Hiroshima, 730-8518, Japan

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KalVista Investigative Site

Saitama, 340-0041, 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

Bialystok, 15-276, Poland

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KalVista Investigative Site

Krakow, 31-503, Poland

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KalVista Investigative Site

Lodz, 92-213, Poland

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KalVista Investigative Site

Porto, 4200-319, Portugal

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KalVista Investigative Site

San Juan, 00918, Puerto Rico

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KalVista Investigative Site

Sângeorgiu de Mureş, Mureș County, 547530, Romania

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KalVista Investigative Site

Martin, 03659, Slovakia

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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

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 1FR, United Kingdom

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Related Publications (3)

• 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.

  PMID: 38819658 BACKGROUND

• 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

• 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.

  PMID: 36774155 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

Results Point of Contact

• Title: Vice President Clinical
• Organization: KalVista Pharmaceuticals Ltd.

clinical@kalvista.com

1 (857) 999-0075

Study Officials

• Study Director

  KalVista Pharmaceuticals, Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: March 2, 2022
• Study Start: February 22, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 2, 2025
• Results First Posted: July 19, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3); IL (4); BU (1); AU (1); RO (1); US (22); DE (4); PT (1); JP (6); GR (2); PR (1); HU (1); NL (1); SL (1); NO (1); FR (4); NZ (1); ES (3); IT (2); GB (5); CA (1)