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)

Phase 3

Active, not recruiting

• Conditions: Hereditary Angioedema
• Interventions: Drug: KVD900 600 mg; Drug: KVD900 300 mg

• Registration Number: NCT05505916
• Lead Sponsor: KalVista Pharmaceuticals, Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-11
• Study First Submitted QC: 2022-08-17
• Study First Posted: 2022-08-18
• Study Start: 2022-10-24
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 145

Inclusion Criteria

1. Confirmed diagnosis of HAE type I or II at any time in the medical history
2. Patient has had at least 2 documented HAE attacks within 3 months prior to the Enrollment Visit.
3. 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).
4. Male or female patients 12 years of age and older.
5. Patients must meet the contraception requirements.
6. Patients must be able to swallow trial tablets whole.
7. 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.
8. Investigator believes that the patient is willing and able to adhere to all protocol requirements.
9. Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required.

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Exclusion Criteria

1. Discontinued from the KVD900-301 trial for reasons of noncompliance, withdrawal of consent, or safety.

2. Presence of any safety concerns that would preclude participation in the open-label trial as determined by the investigator.

3. 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.

4. 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.

5. 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.

6. Use of Angiotensin-converting enzyme (ACE) inhibitors within 7 days prior to the Enrollment Visit.

7. 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.

8. Inadequate organ function, including but not limited to:

   1. Alanine aminotransferase (ALT) >2x Upper Limit 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

9. 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.

10. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.

11. Known hypersensitivity to KVD900 or to any of the excipients.

12. Participation in any gene therapy treatment or trial for HAE.

13. Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to the Enrollment Visit.

14. Any pregnant or breastfeeding patient.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KVD900 600 mg	KVD900 600 mg	-
KVD900 300 mg	KVD900 300 mg	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Patient Global Impression of Change (PGI-C).	within 12 hours of initial dose of IMP administration.	time to beginning of symptom relief defined as at least '' a little better'' (2 time points in a row)
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.	PGI-S: time to HAE attack resolution, defines as ''none''

Trial Locations

Locations (3)

KalVista Investgative Site; 🇯🇵 Tokyo, Japan

KalVista Investigative Site; 🇬🇧 London, United Kingdom

Kalvista Investigative Site; 🇿🇦 Cape Town, South Africa