A Randomized, Double-Blind, Placebo-Controlled, Phase 3, Three-way Crossover Trial to Evaluate the Efficacy and Safety of Two Dose Levels 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

KVD900-301

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

2022-02-23

2023-12-31

2023-12-31

Completed

Early phase I

136

Inclusion Criteria: * 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: 1. has had at least 2 documented HAE attacks within 3 months prior to screening or randomization; or 2. 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. Exclusion Criteria: * 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: 1. Alanine aminotransferase (ALT) \>2x upper limit of 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 * 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. * Participation in any gene therapy treatment or trial for HAE. * Participation in any interventional investigational clinical trial (with the exception of KVD824-201), including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to screening. * Any pregnant or breastfeeding patient.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 136, 'type': 'ACTUAL'}}

2024-01-31