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

Study Overview
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Brief Summary
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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.

Official Title
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An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900, an Oral Plasma Kallikrein Inhibitor, for On-demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema Type I or II

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Drug: KVD900 600 mg


Participation Criteria
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Eligibility Criteria
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Patients may roll over from KVD900-301. Inclusion Criteria: 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. Exclusion Criteria: 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. Known hypersensitivity to KVD900 or to any of the excipients. Participation in any gene therapy treatment or trial for HAE. 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. Any pregnant or breastfeeding patient.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KVD900 600 mg<br> | Drug: KVD900 600 mg<br>* KVD900 Tablet 600 mg (2 x 300 mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with at least one Adverse Event (AE) in adolescent and adult patients with HAE type I or II who have taken at least one dose of Investigational medicinal product (IMP). |  | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change (PGI-C). | time to beginning of symptom relief defined as at least '' a little better'' (2 time points in a row) | 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 | PGI-S: time to HAE attack resolution, defines as ''none'' | within 24 hours of initial dose of IMP administration. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KONFIDENT-S