E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Angioedema Type I or II |
|
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. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 investigate the efficacy of KVD900 compared to placebo in halting the progression of attacks of HAE.
|
|
E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of KVD900 To investigate the pharmacokinetic (PK) profile of KVD900 To investigate the pharmacodynamic (PD) profile of KVD900 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female adult subjects 18 years of age and older. 2. Confirmed diagnosis of HAE type I or II at anytime in the medical history 3. At least 3 documented HAE attacks in the past 93 days, as supported by medical history. 4. Access to and ability to use conventional attack treatment for attacks of HAE. 5. Adequate organ functions as defined below: a. Hemoglobin within normal range; b. International normalized ratio (INR)< 1.2; c. Activated partial thromboplastin time (aPTT) ≤ upper limit of normal (ULN); d. Creatinine < 1.0 g; e. Creatinine clearance (CrCl) ≥ 60 mL/min; f. Alanine aminotransferase (ALT) ≤ 2x ULN; g. Aspartate aminotransferase (AST) ≤ 2x ULN; h. Total bilirubin ≤ 1.5x ULN; i. Leucocytes ≤ 1.5x ULN; j. Thrombocytes ≤ 1.5x ULN. 6. Females of childbearing potential must agree to use highly effective birth control from the last menstrual cycle prior to the start of the study drug until the end of the trial follow-up procedures. 7. Females of non-childbearing potential, defined as surgically sterile or post-menopausal for at least 12 months, do not require contraception during the study. 8. Males with female partners of childbearing potential must agree to be abstinent or else use a medically acceptable form of contraception from the Screening visit through until the end of the trial follow-up procedures. Female partners of males who are surgically sterile, must agree to use one additional form of medically acceptable contraception. 9. Provide signed informed consent and are willing and capable of complying with study requirements and procedures. |
|
E.4 | Principal exclusion criteria |
1. Any concomitant diagnosis of another form of chronic angioedema. 2. Current use of C1INH, androgens, or tranexamic acid for HAE prophylaxis. 3. Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 90 days prior to initial study treatment. 4. Use of androgens or antifibrinolytics within 90 days prior to initial study treatment. 5. Use of strong CYP3A4/CYP2C9 inhibitors and inducers during participation in the trial. 6. Clinically significant abnormal electrocardiogram (ECG) at Visit 1 and pre-dose at Visit 2. 7. Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular abnormality. 8. Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory, cardiovascular) or significant disease or disorder which, in the opinion of the Investigator, would jeopardize the safety of the subject by taking part in the trial. 9. History of substance abuse or dependence that would interfere with the completion of the study, as determined by the Investigator. 10. Known lactose allergy or intolerance. 11. Known hypersensitivity to KVD900 or placebo or to any of the excipients. 12. Participation in an interventional investigational clinical study within 3 months or within 5 half-lives of the last dosing of investigational drug (whichever is longer) prior to initial study treatment. 13. Any pregnant or breast-feeding subject |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoints: • Time to use of conventional attack treatment.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints: • Proportion of HAE attacks that progress by one level or more on the 5LS or that require conventional attack treatment within 12h of study drug. • Time between treatment and (1) progression of global attack severity on the 5LS by one level or more, or (2) use of conventional attack treatment, whichever comes first within 12h |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 2 |
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 | 21 |
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 |
Macedonia, the former Yugoslav Republic of |
|
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |