An Open-Label Study to Evaluate the Long-Term Safety and Efficacy of Lanadelumab for Prevention Against Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 73
- 试验地点
- 35
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period
研究概览
简要总结
The purpose of this study is to evaluate the long-term safety and efficacy of repeated subcutaneous (SC) administration of lanadelumab in adolescents and adults with non-histaminergic angioedema with normal C1-inhibitor who completed study SHP643-303 (NCT04206605).
详细描述
This study consists of 26-week treatment period (Day 0 to Day 182) and a 2-week follow-up period. Participants who completed the double-blind treatment period at Day 182 of Study SHP643-303 (NCT04206605) will enroll into this extension study.
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
- •Males and females, 12 years of age and older diagnosed with non-histaminergic normal C1-INH angioedema at the time of enrollment into the antecedent Study SHP643-303 (NCT04206605).
- •Participants must have completed the treatment period (through Visit 26/Day 182) of Study SHP643-303 (NCT04206605) without reporting a clinically significant TEAE that would preclude subsequent exposure to lanadelumab.
- •Agree to adhere to the protocol-defined schedule of treatments, assessments, and procedures.
- •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; or 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.
- •The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent approved by the institutional review board/research ethics board/ethics committee (IRB/REB/EC) at any time prior to study start. If the participant is a minor (i.e. lesser then (<) 18 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (i.e. permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
排除标准
- •Discontinued from Study SHP643-303 (NCT04206605) after enrollment but before Visit 26 for any reason.
- •Presence of important safety concerns identified in Study SHP643-303 (NCT04206605) that would preclude participation in this study.
- •Dosing with an investigational product (IP, not including IP defined in antecedent Study SHP643-303 [NCT04206605]) or exposure to an investigational device within 4 weeks prior to Day
- •Participants has a known hypersensitivity to the investigational product or its components.
- •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 (e.g. significant pre-existing illness or other major comorbidities that the investigator considers may confound the interpretation of study results).
研究组 & 干预措施
Lanadelumab 300 mg Every 2 Weeks
Participants received 300 milligrams (mg) lanadelumab subcutaneous (SC) injection, every 2 weeks (Q2W) for up to 26 weeks with an option to switch to lanadelumab 300 mg every 4 weeks (Q4W) if attacks were well-controlled based on the investigator's discretion and consultation with the sponsor's medical monitor.
干预措施: Lanadelumab (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Treatment Period
时间窗: From Day 0 up to Day 182
TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP 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. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) During Follow-up
时间窗: From Day 183 up to Day 196
TEAE: Any event emerging or manifesting at or after initiation of treatment with investigational product (IP) or medicinal product or any existing event that worsens in either intensity or frequency following exposure to IP or medicinal product including clinically meaningful findings in laboratory safety tests, vital signs, weight, and electrocardiogram (ECG) findings. SAE: Any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to IP 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. AESI included hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. TEAEs were classified and reported as angioedema attack and non-angioedema attack adverse events in this outcome measure.
次要结局
- Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen(From Day 0 up to Day 182)
- Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182(From Day 0 up to Day 182)
- Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab(Predose on Days 0, 84, and 140 and postdose on Day 182)
- Number of Moderate or Severe Angioedema Attacks During the Treatment Period of Day 0 Through Day 182(From Day 0 up to Day 182)
- Change From Baseline in Total Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at End of Treatment Period(Baseline (Day 0) up to end of treatment period (Day 182))
- Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen(From Day 0 up to Day 182)
- Number of Investigator-Confirmed Angioedema Attacks During the Treatment Period of Day 0 Through Day 182(From Day 0 up to Day 182)
- Plasma Kallikrein (pKal) Activity(Predose on Days 0, 84, and 140 and postdose on Day 182)
- Number of Participants With Neutralizing Antidrug Antibodies (ADA) in Plasma(Predose on Days 0, 84, and 140 and postdose on Day 182)
- Number of Participants With Any Pause During Injection(Days 0, 14, 28, 42, 56, 70, 84, 98, 112, 126, 140, 154, and 168)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs) in Participants Who Switched Dosing Regimen(From Day 0 up to Day 196)
- Number of High-Morbidity Angioedema Attacks During the Treatment Period of Day 0 Through Day 182 in Participants Who Switched Dosing Regimen(From Day 0 up to Day 182)