E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Angioedema Type I or II |
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E.1.1.1 | Medical condition in easily understood language |
Hereditary Angioedema is a genetic condition characterised by swelling of tissues. These swellings can occur on any part of the body. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080956 |
E.1.2 | Term | Hereditary angioedema type I |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 26.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10080960 |
E.1.2 | Term | Hereditary angioedema type II |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the clinical efficacy of KVD900 compared with placebo for the on-demand treatment of HAE attacks. |
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E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of KVD900. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female patients 12 years of age and older. 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 have been 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 a) has had at least 2 documented HAE attacks within 3 months prior to screening or randomization: or b) ) 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. |
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E.4 | Principal 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) Patients who require sustained use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. 6) Inadequate organ function, including but not limited to: a) Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) b) Aspartate aminotransferase (AST) >2x ULN c) Bilirubin direct >1.25x ULN d) International normalized ratio (INR) >1.2 e) 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 l (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. 13) Any pregnant or breastfeeding patient. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 12 hours of the first IMP administration. |
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E.5.2 | Secondary end point(s) |
• PGI-S: Time to first incidence of decrease from baseline (2 time points in a row) within 12 hours of the first IMP administration. • PGI-S: Time to HAE attack resolution defined as “none” within 24 hours of the first IMP administration • 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. • PGI-C: Time to at least “better” (2 time points in a row) within 12 hours of the first IMP administration. • PGI-S: Time to first incidence of decrease from baseline (2 time points in a row) within 24 hours of the first IMP administration. • 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Within 12 hours of the first IMP administration. Within 24 hours of the first IMP administration. Within 4 hours and within 12 hours of the first IMP administration. Within 12 hours of the first IMP administration. Within 24 hours of the first IMP administration. Within 12 hours and within 24 hours of the first IMP administration |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Dose Ranging |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
New Zealand |
North Macedonia |
Australia |
Bulgaria |
Canada |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Japan |
Netherlands |
Poland |
Portugal |
Romania |
Slovakia |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 5 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |