A Multi-center, Open-label Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Lanadelumab (SHP643) in Chinese Subjects With Hereditary Angioedema
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
研究概览
简要总结
The main aim of this study is to evaluate the safety of lanadelumab in Chinese participants with HAE.
Participants will be treated with lanadelumab for 26 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be of Chinese descent, defined as born in China and having Chinese parents and Chinese maternal and paternal grandparents.
- •The participant is male or female and greater than or equal to (>=) 12 years of age at the time of informed consent.
- •Documented diagnosis of HAE Type I or Type II based upon all of the following:
- •Documented clinical history consistent with HAE (subcutaneous [SC] or mucosal, nonpruritic swelling episodes without accompanying urticaria).
- •Diagnostic testing results obtained during screening by a laboratory (approved by the sponsor) that confirm HAE Type I or Type II: C1 esterase inhibitor (C1-INH) functional level <40% of the normal level. Participants with functional C1-INH level 40% to 50% of the normal level may be enrolled if they also have a C4 level below the normal range. Participants may begin participating in the run-in period before these diagnostic results are available. Participants may be re-tested if results are incongruent with clinical history or believed by the investigator to be confounded by recent long-term prophylaxis (LTP) use.
- •At least one of the following: Age at reported onset of first angioedema symptoms less than or equal to (<=) 30 years, a family history consistent with HAE Type I or Type II, or C1q within normal range.
- •Attack rate:
- •At the time of enrollment, participants must experience at least 1 investigator-confirmed HAE attack per 4 weeks during the run-in period.
- •The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board (IRB)/ institutional ethical committee (IEC).
- •If the participant is an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
- •If the participant is a minor (that is <18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (that is, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
- •Males, or non-pregnant, non-lactating females who are fertile and sexually active and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study, or females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or postmenopausal for at least 12 months.
- •Agree to adhere to the protocol-defined schedule of assessments and procedures.
排除标准
- •Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema, HAE with normal C1 esterase inhibitor (C1-INH) (also known as HAE Type III), idiopathic angioedema, or recurrent angioedema associated with urticaria.
- •Participation in a prior lanadelumab study or use any lanadelumab prior to the study.
- •Dosing with investigational drug or exposure to an investigational device within 4 weeks prior to entering to screening.
- •Exposure to angiotensin-converting enzyme inhibitors or any estrogen-containing medications with systematic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
- •Exposure to androgens (that is, danazol, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period.
- •Use of LTP therapy (defined as continued use) for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) for adult participants within 2 weeks prior to entering the run-in period. Adolescent participants (>=12 to <18 years of age) who are on LTP therapy for HAE are allowed to enter the study.
- •Use of short-term prophylaxis for HAE 7 days prior to entering the run-in period. Short-term prophylaxis is defined as fresh frozen plasma (FFP), C1-INH, attenuated androgens, or antifibrinolytics used to avoid angioedema complications from medically indicated procedures. Note: Currently, C1-INH therapies are not available in China.
- •Any of the following liver function abnormalities: alanine aminotransferase (ALT) greater than (>) 3* upper limit of normal (ULN), or aspartate aminotransferase (AST) > 3* ULN or bilirubin > 2* ULN (unless the bilirubin is a result of Gilbert's syndrome).
- •Pregnancy or breast feeding.
- •Participant has any condition that in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (example, history of substance abuse or dependence, significant pre-existing illnesses or major comorbidity the investigator considers may confound the interpretation of the study results).
研究组 & 干预措施
Lanadelumab 300 mg
Participants received lanadelumab 300 milligrams (mg), subcutaneously (SC), once every 2 weeks (Q2W) from Day 0 to Day 182 (26 weeks).
干预措施: Lanadelumab (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
时间窗: From first dose of study drug up to end of study (up to Day 210)
TEAE is defined as an adverse event (AE) with onset at the time of or following initial dosing with study drug (lanadelumab), or medical conditions present prior to the start of study drug but increasing in severity or relationship at the time of or following the start of treatment, up to the last follow-up visit. An SAE is any untoward clinical manifestation of signs, symptoms or outcomes whether considered related to investigational product or not and at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. Hypersensitivity reactions and events of disordered coagulation were considered as AESIs. Adverse events were classified as HAE attack and non-HAE attack reported AEs and are categorized accordingly in this outcome measure. A participant could be counted in more than one category.
Number of Participants With Clinically Meaningful Changes in Clinical Laboratory Parameters
时间窗: From first dose of study drug up to end of study (up to Day 210)
Laboratory parameters included clinical chemistry, hematology, coagulation, urinalysis, and serology. Clinically meaningful laboratory parameters assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in laboratory parameters (including clinical chemistry, hematology, coagulation, urinalysis, and serology) were reported.
Number of Participants With Clinically Meaningful Changes in Vital Sign Abnormalities
时间窗: From first dose of study drug up to end of study (up to Day 210)
Vital signs included measurement of blood pressure, heart rate, body temperature, and respiratory rate. Clinically meaningful vital signs assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in vital signs were reported.
Number of Participants With Clinically Meaningful Changes in Electrocardiogram (ECG)
时间窗: From first dose of study drug up to end of study (up to Day 210)
ECG included heart rate, PR interval, QRS duration, QT interval, corrected QT interval (QTc) interval, QT corrected for heart rate by Fridericia's cube root formula (QTcF) interval, and QT corrected for heart rate by Bazett formula (QTcB) interval. Clinically meaningful ECG assessment was based on investigator interpretation. Number of participants with clinically meaningful changes in ECG were reported.
Number of Participants With Clinically Significant Physical Examination Abnormalities on Day 182
时间窗: Day 182
Physical examination findings by body system were classified as height and weight, general appearance, ears, nose and throat, head and neck, ophthalmological, respiratory, cardiovascular, abdomen, neurological, extremities, dermatological, and lymphatic. Number of participants with clinically significant changes in physical examination findings per investigator interpretation were reported. Only categories with at least one participant with event are reported.
次要结局
- Plasma Concentrations of Lanadelumab(Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182)
- Plasma Kallikrein (pKal) Activity(Anytime on Days 0 and 210; and pre-dose on Days 14, 56, 98, 140, 182)
- Number of Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Number of Investigator-Confirmed HAE Attacks That Required Acute Treatment During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Number of Moderate or Severe Investigator-Confirmed HAE Attacks During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Number of Participants With Maximum Attack Severity During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Number of Participants Who Achieved Investigator-confirmed HAE Attack-Free Status During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Time to First Investigator-confirmed HAE Attack During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Number of Participants Who Achieved at Least 50%, 70%, 90%, and 100% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA(Day 0 through Day 182)
- Number of Participants Who Achieved NNA <1.0 Per 4 Weeks for the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)
- Number of Participants With Neutralizing or Non-neutralizing Antidrug Antibodies (ADA) in Plasma(Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182)
- Plasma Concentrations of Lanadelumab by Immunogenicity Result(Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182)
- Plasma Kallikrein Activity cHMWK by Immunogenicity Result(Anytime on Days 0 and 210; and pre-dose on Days 56, 98, 140, 182)
- Number of Investigator-confirmed HAE Attacks by Immunogenicity Result During the Efficacy Evaluation Period of Day 0 Through Day 182(Day 0 through Day 182)