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

NCT04208412 | Completed Phase 2 Results FDA Drug

• 1 other identifier: KVD900-201
• Study Type: interventional
• Target: 84
• Locations: 10 countries
• Sites: 25

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

Keywords

Sebetralstat

Outcome Measures

Primary Outcomes (1)

• Time to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)

  The primary variable for statistical comparison between treatments in Part 2 of the study was time to use of conventional attack treatment (pdC1INH or rhC1INH intravenous \[iv\] or icatibant) within 12 hours of study drug. Censoring occurs where a subject did not use conventional attack treatment within 12h post-study drug dosing. When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

  12 hours

Secondary Outcomes (4)

• Proportion of HAE Attacks That Worsen in Severity by One Level or More on the PGI-S or Require Conventional Attack Treatment Within 12 Hours of Study Drug (Full Analysis Set)

  12 hours

• Time to Either Worsening in HAE Attack Severity by One Level or More on the PGI-S or to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)

  12 hours

• Time to Symptom Relief Defined as HAE Attack Rated as "A Little Better" or Higher on the PGI-C for Two Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)

  12 hours

• Time to Symptom Relief Defined as 50% Reduction in Composite VAS Score for Three Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)

  12 hours

Study Arms (3)

Part 1

EXPERIMENTAL

Subjects received a single dose of 600 mg KVD900.

Drug: KVD900

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

EXPERIMENTAL

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.

Drug: KVD900; Other: Placebo

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

EXPERIMENTAL

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.

Drug: KVD900; Other: Placebo

Interventions

KVD900 DRUG

KVD900 tablet 600 mg

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

Placebo OTHER

KVD900-matched Placebo Tablet

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

Eligibility Criteria

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

You may qualify if:

• 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
• Provide signed informed consent and are willing and capable of complying with study requirements and procedures

You may not qualify if:

• 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

Sponsors & Collaborators

• KalVista Pharmaceuticals, Ltd.: lead

Study Sites (25)

KalVista Investigative Site

Scottsdale, Arizona, 85251, United States

Location

KalVista Investigative Site

Centennial, Colorado, 80112, United States

Location

KalVista Investigative Site

Chevy Chase, Maryland, 20815, United States

Location

KalVista Investigative Site

Cincinnati, Ohio, 45231, United States

Location

KalVista Investigative Site

Dallas, Texas, 75231, United States

Location

KalVista Investigative Site

Spokane, Washington, 99204, United States

Location

KalVista Investigative Site

Vienna, Austria

Location

KalVista Investigative Site

Brno, Czechia

Location

KalVista Investigative Site

Hradec Králové, Czechia

Location

KalVista Investigative Site

Pilsen, Czechia

Location

KalVista Investigative Site

Berlin, Germany

Location

KalVista Investigative Site

Frankfurt, Germany

Location

KalVista Investigative Site

Mörfelden-Walldorf, Germany

Location

KalVista Investigative Site

Budapest, Hungary

Location

KalVista Investigative Site

Milan, 1, Italy

Location

KalVista Investigative Site

Milano-2, Italy

Location

KalVista Investigative Site

Padua, Italy

Location

KalVista Investigative Site

Amsterdam, Netherlands

Location

KalVista Investigative Site

Skopje, North Macedonia

Location

KalVista Investigative Site

Krakow, Poland

Location

KalVista Investigative Site

Warsaw, Poland

Location

KalVista Investigative Site

Camberley, United Kingdom

Location

KalVista Investigative Site

Cambridge, United Kingdom

Location

KalVista Investigative Site

London, United Kingdom

Location

KalVista Investigative Site

Newcastle, United Kingdom

Location

Related Publications (1)

• 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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 23, 2019
• Study Start: July 2, 2019
• Primary Completion: December 8, 2020
• Study Completion: December 8, 2020
• Last Updated: May 2, 2025
• Results First Posted: February 8, 2023

Record last verified: 2025-04

Locations

DE (3); NO (1); NL (1); IT (3); US (6); AU (1); GB (4); PL (2); HU (1); CZ (3)