A randomized, double-blind, placebo-controlled, phase II, cross-over clinical trial evaluating the efficacy and safety of KVD900, an oral plasma kallikrein inhibitor, in the on-demand treatment of angioedema attacks in adult subjects with hereditary angioedema type I or II
- Conditions
- Hereditary Angioedema Type I or IIswelling of tissues10003816
- Registration Number
- NL-OMON48423
- Lead Sponsor
- KalVista Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
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 < 1x ULN;
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. Female of childbearing potential must agree to use highly effective birth
control from the Screening visit until the end of the trial follow-up
procedures.
7. Females of non-childbearing potential, defined as surgically sterile (status
post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) 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 highly effective method of birth control as defined in
inclusion criterion 6 from the Screening visit until the end of the trial
follow-up procedures.
9. Provide signed informed consent and are willing and capable of complying
with study requirements and procedures.
1. Any concomitant diagnosis of another form of chronic angioedema, such as
acquired C1 inhibitor deficiency, HAE with normal C1-INH (also known as HAE
type III), idiopathic angioedema, or
angioedema associated with urticaria.
2. Current use of C1INH, androgens, lanadelumab or tranexamic acid for HAE
prophylaxis.
3. Use of angiotensin-converting enzyme (ACE) inhibitors or any
estrogen-containing medications with systemic absorption (such as oral
contraceptives or hormonal replacement therapy) within
93 days prior to initial study treatment.
4. Use of androgens (e.g. stanozolol, danazol, oxandrolone,
methyltestosterones, testosterone) or antifibrinolytics within 30 days prior to
initial study treatment.
5. Use of lanadelumab within 10 weeks prior to initial study treatment
6. Use of strong CYP3A4/CYP2C9 inhibitors and inducers during participation in
the trial.
Note: These medications include but are not limited to the following:
cobicistat, conivaptan, itraconazole, ketoconazole, posaconazole, voriconazole,
ritonavir, boceprevir, telaprevir, troleandomycin, clarithromycin,
carbamazepine, enzalutamide, mitotane, phenytoin,
phenobarbital, fluconazole, isoniazid, metronidazole, paroxetine,
sulfamethoxazole, rifampicin, St. John*s Wort, diltiazem, idelalisib,
nefazodone and nelfinavir.
7. Clinically significant abnormal electrocardiogram (ECG) at Visit 1 and
pre-dose at Visit 2. This includes, but is not limited to, a QTcF > 470 msec
(for women) or > 450 msec (for men), a
PR > 220 msec or ventricular and/or atrial premature contractions that are more
frequent than occasional and/or occur as couplets or higher in grouping.
8. Any clinically significant history of angina, myocardial infarction,
syncope, clinically significant cardiac arrhythmias, left ventricular
hypertrophy, cardiomyopathy, or any other cardiovascular
abnormality.
9. 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.
10. History of substance abuse or dependence that would interfere with the
completion of the study, as determined by the Investigator.
11. Known lactose allergy or intolerance.
12. Known hypersensitivity to KVD900 or placebo or to any of the excipients.
13. Participation in an interventional investigational clinical study within 93
days or within 5 half-lives of the last dosing of investigational drug
(whichever is longer) prior to initial study treatment.
14. Any pregnant or breast-feeding subject.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoints:<br /><br>• Time to use of conventional attack treatment.</p><br>
- Secondary Outcome Measures
Name Time Method