Hereditary angioedema (HAE) type I or type II. Haematological Disorders Hereditary Angioedema Type I or II
Conditions
Interventions
Patients will be assigned to receive 3 treatments in randomized, double-dummy blinded, crossover fashion based on their assignment to 1 of 6 treatment sequences. Randomization will occur in a 1:1:1:1:
Sponsors
KalVista Pharmaceuticals Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 26/10/2023: 1. Male or female patients 12 years of age and older with a weight of >30 kg 2. Confirmed diagnosis of HAE type I or II at any time in the medical history. 3. Patient has access to and ability to use conventional on-demand treatment for HAE attacks. 4. 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 and be willing to remain on a stable dose and regimen for the duration of the trial. 5. Patient’s last dose of attenuated androgens was at least 28 days prior to randomization. 6. Patient: 6.1. Has had a least two documented HAE attacks within 3 months prior to screening or randomisation; or 6.2. Is a completer of the KVD824-201 trial within 3 months prior to randomization and meets all other entry criteria to enroll in KVD900-301.7. Patients must meet the contraception requirements. 8. Patients must be able to swallow trial tablets whole. 9. 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). 10. Investigator believes that the patient is willing and able to adhere to all protocol requirements. 11. Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required. _____ Previous inclusion criteria as of 04/11/2022: 1. Male or female patients 12 years of age and older with a weight of >30kg 2. Confirmed diagnosis of HAE type I or II at any time in the medical history. 3. Patient has access to and ability to use conventional on-demand treatment for HAE attacks. 4. 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 and be willing to remain on a stable dose and regimen for the duration of the trial. 5. Patient’s last dose of attenuated androgens was at least 28 days prior to randomization. 6. Patient: 6.1. Has had at least two documented HAE attacks within 3 months prior to randomization; or 6.2. Is a completer of the KVD824-201 trial within 3 months prior to randomization and meets all other entry criteria to enroll in KVD900-301.7. Patients must meet the contraception requirements. 8. Patients must be able to swallow trial tablets whole. 9. 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). 10. Investigator believes that the patient is willing and able to adhere to all protocol requirements. 11. Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required. _____ Previous inclusion criteria: 1. Male or female patients 12 years of age and older with a weight of >30kg 2. Confirmed diagnosis of HAE type I or II at any time in the medical history. 3. Patient has access to and ability to use conventional on-demand treatment for HAE attacks. 4. If a patient is receiving long-term prophylactic treatment with one of these medicines indicated for HAE: intravenous (iv) or sc plasma-derived C1-INH, and/or lanadelumab, they must be on a stable dose and re
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 04/11/2022: 1. 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. 2. 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. 3. Use of angiotensin-converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization. 4. 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. 5. Patients who require sustained use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. 6. Inadequate organ function, including but not limited to: 6.1. Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) 6.2. Aspartate aminotransferase (AST) >2x ULN 6.3. Bilirubin direct >1.25x ULN 6.4. International normalized ratio (INR) >1.2 6.5. Clinically significant hepatic impairment defined as a Child-Pugh B or C 7. 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. 8. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator. 9. Known hypersensitivity to KVD900 or placebo or to any of the excipients. 10. Prior participation in trial KVD900-201. 11. Participation in any gene therapy treatment or trial for HAE. 12. 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 the investigational drug prior to screening. 13. Any pregnant or breastfeeding patient. _____ Previous exclusion criteria: 1. 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. 2. 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. 3. Use of angiotensin-converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization. 4. 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. 5. Use of strong cytochrome P450 3A4 (CYP3A4) inhibitors and inducers during participation in the trial, starting within 5 half-lives of the Screening Visit. 6. Inadequate organ function, including but not limited to: 6.1. Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) 6.2. Aspartate aminotransferase (AST) >2x ULN 6.3. Bilirubin direct >1.25x ULN 6.4. International normalized ratio (INR) >1.2 6.5. Clinically significant hepatic impairment defined as a Child-Pugh B or C 7. Any clinically significant comorbidity or systemic dysfunction, which in the opinion of the Investigator, would jeopardize the safety of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PGI C: Time to beginning of symptom relief defined as at least “a little better” (2 timepoints in a row) within 12 hours of the first IMP administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 26/10/2023: 1. PGI-S: Time to first incidence of decrease from baseline (2 time points in a row) within 12 hours of the first IMP administration. 2. PGI-S: Time to HAE attack resolution defined as “none” within 24 hours of the first IMP administration 3. PGI-C: Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row) within 4 hours and within 12 hours of the first IMP administration 4. PGI:C Time to at least "better" (2 time points in a row) within 12 hours of the first IMP administration. 5. PGI:S: Time to first incidence of decrease from baseline (2 time points in a row) within 24 hours of the first IMP administration. 6. Composite VAS: Time to at least a 50% decrease from baseline (3 time points in a row) within 12 hours and within 24 hours of the first IMP administration _____ Previous secondary outcome measures: 1. PGI-S: Time to first incidence of decrease from baseline within 12 hours of the first IMP administration 2. PGI-S: Time to HAE attack resolution defined as “none” within 24 hours of the first IMP administration 3. PGI-C: Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row) within 4 hours and within 12 hours of the first IMP administration 4. PGI-C: Time to at least "better" within 12 hours of the first IMP administration 5. PGI-S: Time to first incidence of decrease from baseline within 24 hours of the first IMP administration 6. Composite VAS: Time to at least a 50% decrease from baseline (3 time points in a row) within 12 hours and within 24 hours of the first IMP administration | — |
Countries
Australia, Bulgaria, Canada, France, Germany, Greece, Hungary, Israel, Italy, Japan, Macedonia, Netherlands, New Zealand, Poland, Portugal, Romania, Slovakia, Spain, United Kingdom, United States of America
Outcome results
None listed