A Randomized, Double-Blind, Placebo-Controlled, Phase 3, Three-way Crossover Trial to Evaluate the Efficacy and Safety of Two Dose Levels 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: jRCT2051220178

Registered date:28/02/2023

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Hereditary Angioedema
• Date of first enrollment: 18/04/2023
• Target sample size: 12
• Countries of recruitment: United States,Japan,Canada,Japan,Australia,Japan,New Zealand,Japan,Bulgaria,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,North Macedonia,Japan,Poland,Japan,Puerto Rico,Japan,Romania,Japan,Spain,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

- 300 mg KVD900 (1 x 300 mg tablet plus 1 matching placebo tablet)
- 600 mg KVD900 (2 x 300 mg tablets)
- 2 matching placebo tablets

Outcome(s)

• Primary Outcome: To demonstrate the clinical efficacy of KVD900 compared with placebo for the on-demand treatment of HAE attacks.
• Secondary Outcome: To investigate the safety and tolerability of KVD900.

Key inclusion & exclusion criteria

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

Include 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:
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.
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) Patients 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 one of the following contraception requirements as follows:
a) Female patients who are fertile and heterosexually active must agree to use contraception from the Screening Visit until the Final 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 7a).
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 and remain premenarcheal until the end of the trial.
c) Male patients (including female partners) do not require contraception.
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 must also provide signed informed consent when required.

Exclude criteria

1) Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1-inhibitordeficiency, 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-INHtherapy, 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 orinducers.
Note: These medications include but are not limited to the following:
Inhibitors: boceprevir, clarithromycin, cobicistat, dasabuvir, denoprevir, elvitegravir, idelalisib,indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir ombitasvir, paritaprevir,posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, andvoriconazole.
Inducers: apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. Johns Wort.
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 (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.

Related Information

• Primary Sponsor: Smith Michael
• Secondary ID(s): NCT05259917