An Open-label Extension Trial to Evaluate the Long-term Safety 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

JRCT ID: jRCT2061230005

Registered date:12/04/2023

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Hereditary Angioedema
• Date of first enrollment: 17/08/2023
• Target sample size: 150
• Countries of recruitment: United States,Japan,Australia,Japan,Bulgaria,Japan,France,Japan,Hungary,Japan,Netherlands,Japan,Spain,Japan,Greece,Japan,United Kingdom,Japan
• Study type: Interventional
• Intervention(s): The IMP in this trial will be the FCT prior to the IMP Exchange Visit; however, patients will switch to using the ODT after the IMP Exchange Visit. For film-coated tablets, patients will self-administer a single dose of 600 mg KVD900 (2 x 300 mg tablets). Patients will be permitted to take a second dose of 600 mg separated by at least 3 hours following the first dose if attack symptoms persist without improvement. For orodispersible tablets, patients will self-administer a single dose of 300 mg KVD900 (1 x 300 mg ODT). Patients will be permitted to take additional doses of 300 mg if attack symptoms are considered severe enough by the patient to require additional treatment. No more than 3 total doses of IMP (i.e. 900 mg TDD) may be taken within 24 hours.

Outcome(s)

• Primary Outcome: The primary objective of this trial is to assess the safety of long-term administration of KVD900 in adolescent and adult patients with HAE type I or II.

Secondary Outcome

- To assess the long-term efficacy of KVD900 in the treatment of attacks in adolescent and adult patients with HAE type I or II.
- To assess the safety and efficacy of KVD900 when used as short-term prophylaxis in adolescent and adult patients with HAE types I or II.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Rollover Patients
1R) Randomized in the KVD900-301 trial.
Non-Rollover Patients
1NR) Confirmed diagnosis of HAE type I or II at any time in the medical history:
a) Documented clinical history consistent with HAE (sc or mucosal, nonpruritic swelling episodes without accompanying urticaria) AND EITHER
i) Diagnostic testing results obtained prior to randomization that confirm HAE type I or II: C1-INH functional level <40% of the normal level. Patients with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. Testing may be obtained from central or local laboratories or obtained from documented historical testing results. Patients may be retested at any time prior to randomization if results are incongruent with clinical history or believed by the Investigator to be confounded by recent prophylactic or therapeutic C1-INH use, OR
ii) Documented genetic results that confirm known mutations for HAE type I or II.
2NR) Patient has had at least 2 documented HAE attacks within 3 months prior to the Enrollment Visit.
3NR) 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 Enrollment Visit.
All Patients (AP)
1AP) Male or female patients 12 years of age and older.
2AP) Patients must meet one of the following contraception requirements as follows:
a) Female patients who are fertile and heterosexually active must agree to use contraception from the Enrollment Visit until the EOS or Early Termination (ET) Visit. Acceptable methods of contraception include one or more of the following:
i) Intrauterine device.
ii) Intrauterine hormone-releasing system.
iii) Bilateral tubal occlusion.
iv) Vasectomized partner (provided that the partner is the sole heterosexual partner of the female patient of childbearing potential and that the vasectomized partner has received medical assessment of surgical success).
v) Male condom.
b) Patients who are not fertile or not heterosexually active, as defined below, do not require contraception. If the patients status changes during the course of the trial, they will be required to meet the requirements specified in Inclusion Criterion 2AP.
i) Female patients who refrain from heterosexual intercourse during the trial if the reliability of the heterosexual abstinence has been evaluated in relation to the duration of the clinical trial and is the preferred and usual lifestyle of the patient.
ii) Female patients who are surgically sterile (e.g. status post hysterectomy, bilateral
oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months.
iii) Female patients who are premenarche.
c) Male patients (including female partners) do not require contraception.
3AP) Patients must be able to swallow trial tablets whole.
4AP) Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.
5AP) Investigator believes that the patient is willing and able to adhere to all protocol requirements.
6AP) Patient provides signed informed consent or assent (when applicable). A parent or LAR must also provide signed informed consent when required.

Exclude criteria

Rollover Patients
1R) Discontinued from the KVD900-301 trial for reasons of non-compliance, withdrawal of consent, or safety.
2R) Presence of any safety concerns that would preclude participation in the open-label trial as determined by the investigator.
Non-Rollover Patients
1NR) 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.
2NR) 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.
3NR) Use of attenuated androgens (e.g. stanozolol, danazol, oxandrolone, methyltestosterone, testosterone), or anti-fibrinolytics (e.g. tranexamic acid) within 28 days prior to the Enrollment Visit.
4NR) Use of angiotensin-converting enzyme (ACE) inhibitors within 7 days prior to the Enrollment Visit.
5NR) Any estrogen-containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Enrollment Visit.
6NR) Inadequate organ function, including but not limited to:
a) Alanine aminotransferase (ALT) >2x 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
7NR) 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.
8NR) History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
9NR) Known hypersensitivity to KVD900 or to any of the excipients.
10NR) Participation in any gene therapy treatment or trial for HAE.
11NR) Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to the Enrollment Visit.
12NR) Any pregnant or breastfeeding patient.

Related Information

• Primary Sponsor: Smith Michael
• Secondary ID(s): NCT05505916