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)

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

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

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.