A Phase 3, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema with Normal C1-Inhibitor (C1-INH)

Dyax Corporation, a Takeda company0 个研究点目标入组 75 人开始时间: 2020年8月31日最近更新: 2021年5月17日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 75

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•Inclusion criteria 1 through 3 and 6 through 10 are identical for the 2 study populations, non-histaminergic normal C1-INH angioedema and AAE due to C1-INH deficiency:
•1. Males and females, 12 years of age and older for subjects with non-histaminergic normal C1-INH angioedema or 30 years of age and older for subjects with AAE due to C1-INH deficiency at the time of signing of the informed consent form (ICF).
•2. Documented clinical history of recurrent attacks of angioedema in the absence of wheals/urticaria.
•3. Investigator-confirmed diagnosis of non-histaminergic bradykinin-mediated angioedema:
•A) non-histaminergic angioedema with normal C1-INH or
•B) AAE due to C1-INH deficiency, as documented by a history of angioedema attacks at screening and occurrence of attack(s) during the observation period.
•4. Subjects with non-histaminergic normal C1-INH angioedema must also meet the specific inclusion criteria below unique to this study population:
•- History of recurrent angioedema with at least an average of 1 angioedema attack per 4 weeks prior to screening and this attack rate must be confirmed during the observation period while treated with chronic high-dose antihistamine (cetirizine 40 mg/day or equivalent high-dose second-generation antihistamine medication).
•- Diagnostic testing results obtained during screening from a sponsor-approved central laboratory that confirm C1-INH antigen and function =50% of normal and normal C4. With prior sponsor approval, subjects may be retested during the observation period if results are incongruent with clinical history.
•- Clinical history of not responding to high-dose antihistamine treatment (cetirizine 40 mg/day or equivalent high-dose second-generation antihistamine medication), which must be confirmed during the observation period with at least 1 angioedema attack per 4 weeks with chronic high-dose antihistamine treatment and no significant difference (as assessed by the investigator and in consultation with the sponsor’s medical monitor, as necessary) from the historic attack rate without high-dose antihistamine treatment.
•5. Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures. Subjects =18 years of age must be willing to use icatibant as the rescue medication during the observation and treatment period. During the observation period, subjects need to be treated with icatibant for at least 2 angioedema attacks or at least 1 moderate or severe attack. In the opinion of the investigator, subjects with no response to icatibant for acute angioedema attacks in the past medical history/screening, or no improvement or worsened attack severity 2 hours after icatibant treatment during the observation period (based on totality of assessments), will not be included. Note: For subjects 12 to <18 years of age, standard of care therapy per local protocols should be provided.
•8. Males, or non-pregnant, non-lactating females who are of child-bearing potential and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and must be willing to undergo pregnancy tests throughout the study. 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.
•9. The subject (o

排除标准

•Except for exclusion criterion 4, all other exclusion criteria listed below are identical for the 2 study populations.
•1. Concomitant diagnosis of Type I or Type II HAE, or recurrent angioedema associated with urticaria.
•2. Dosing with any investigational drug or exposure to an investigational device within 4 weeks prior to screening.
•3. Exposure to angiotensin-converting enzyme (ACE) inhibitors or rituximab within 6 months prior to screening.
•4. Use of any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
•5. Response to omalizumab (prophylactic) or corticosteroid (acute/prophylactic) or epinephrine (acute) or anti-leukotrienes (prophylactic) treatments in the past.
•6. Use of long-term prophylactic therapy for HAE, eg, C1-INH, attenuated androgens (eg, danazol, methyltestosterone, testosterone), or anti-fibrinolytics within 2 weeks prior to entering the observation period as long as the investigator determines that doing so would not place the subject at any undue risk, and that the subject is at least 18 years of age.
•7. Any exposure to prophylactic plasma kallikrein inhibitors prior to screening.
•8. Use of short-term prophylaxis for HAE within 7 days prior to entering the observation period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or antifibrinolytics used to avoid angioedema complications from medically indicated procedures.
•9. Have any active infectious illness or fever defined as an oral temperature >38°C (100.4°F), tympanic >38.5°C (101.3°F), axillary >38°C (100.4°F), or rectal/core >38.5°C (101.3°F) within 24 hours prior to the first dose of study drug in the treatment period. Any angioedema attack must be resolved prior to the first dose in the treatment period.
•10. Any of the following liver function test abnormalities: ALT >3x upper limit of normal, or AST >3x upper limit of normal, or total bilirubin >2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert’s syndrome).
•11. Pregnancy or breast feeding.
•12. Subject has a known hypersensitivity to the investigational product or its components.
•13. Have any uncontrolled underlying medical condition which would require treatment adjustment during the study treatment period, that, in the opinion of the investigator or sponsor, may confound the results of the safety assessments or may place the subject at risk. Subjects with stable treatment for at least 3 months prior to screening and NOT expecting any change to their treatment regimen for 6 months during the study treatment period, will not be excluded.
•14. Have any condition (surgical or medical) that, in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude the successful conduct of the study, or interfere with interpretation of the results (eg, significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).

研究者

发起方

Dyax Corporation, a Takeda company

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