A Multicenter, Open-Label, Non-Randomized Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Administration of Icatibant in Children and Adolescents With Hereditary Angioedema
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 32
- 试验地点
- 26
- 主要终点
- Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant
研究概览
简要总结
HGT-FIR-086 is a multicenter, open-label, non-randomized, single-arm study to evaluate the Pharmacokinetics, tolerability,safety, and efficacy on reproductive hormones, of a single subcutaneous (SC) administration of icatibant in approximately 30 pediatric subjects with Hereditary Angioedema (HAE) during an initial acute attack.
详细描述
Study HGT-FIR-086 will enroll 30 subjects from 2 to less than 18 years of age, divided into 2 groups: prepubertal and pubertal/postpubertal. At least 10 prepubertal children and at least 20 adolescents (including 10 treated during a HAE attack) must be enrolled in the study.
After a qualifying screening period, the PK, safety/tolerability, and efficacy of treatment with SC icatibant will be evaluated in at least 20 subjects (10 prepubertal and 10 pubertal/postpubertal subjects) who present with cutaneous, abdominal, or laryngeal symptoms of an acute attack of HAE. The PK and safety/tolerability of SC icatibant will be evaluated in at least 10 additional pubertal/postpubertal subjects who meet screening criteria and receive treatment with SC icatibant in the absence of a current acute HAE attack.
The planned duration of active participation for subjects who present with an initial attack of acute HAE will consist of treatment with a single subcutaneous injection of icatibant on Day 1 through follow up at day 90.
After having received initial treatment with icatibant, either during or in the absence of an attack, at least 10 pubertal/postpubertal subjects who subsequently experience an acute HAE attack may continue to receive treatment with icatibant as a single SC administration per attack for a total of 3 eligible icatibant-treated attacks.
The period of active participation in the study for prepubertal subjects will be approximately 90 days, while that for pubertal/postpubertal subjects could be a maximum of approximately 270 or 360 days (3 separate active periods of approximately 90 days for those treated with icatibant during an attack; 4 separate active periods for those treated without an attack), with each active period separated by periods of inactive participation of variable duration.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Two through <18 years of age at the time of first HAE attack.
- •Prepubertal and pubertal/postpubertal subjects experiencing and acute cutaneous, abdominal, or laryngeal HAE attack treated with icatibant as part of this study.
- •Pubertal/postpubertal subjects with HAE who are treated with icatibant, but not during an attack.
- •Documented diagnosis of HAE Type I or II.
- •Informed consent (and subject assent as appropriate) signed by the subject's parent(s)or legal guardian(s).
排除标准
- •Diagnosis of angioedema other than HAE.
- •Participation in another clinical trial that involves the use of any investigational product (drug or device)within 30 days prior to study enrollment or at any time during the study.
- •Any known factor/disease that might interfere with the treatment compliance, study conduct,or result interpretation.
- •Congenital or acquired cardiac anomalies that interfere significantly with cardiac function.
- •Treatment with ACE inhibitors within 7 days prior to treatment.
- •Use of hormonal contraception within the 90 days prior to treatment.
- •Androgen use (eg, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within the 90 days prior to treatment.
- •Pregnancy or breastfeeding.
- •A physical condition that interferes with pubertal status determination.
研究组 & 干预措施
Icatibant
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
干预措施: icatibant (Drug)
结局指标
主要结局
Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Elimination half-life (t1/2) of a single SC dose of icatibant was reported.
Number of Participants With Clinically Significant Changes in Vital Signs
时间窗: Pre-dose up to 97 days post-dose
Vital signs included pulse rate, blood pressure, respiration rate, and temperature. The number of participants who reported clinically significant changes in vital signs were reported.
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)
时间窗: 6 - 8 hours post-dose on Day 1
A standard 12-lead ECG was performed after 10 minutes at rest when the participant was seated or supine following treatment. The number of participants who reported clinically significant changes in ECGs were reported.
Number of Participants With Adverse Events (AEs)
时间窗: From the start of study drug administration up to 97 days post-dose
An AE was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in a clinical study, whether or not considered investigational product related.
Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1
时间窗: 1 h post-dose on Day 1 up to 9 days post-dose
The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occured after initial icatibant administration was reported.
Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Time to peak concentration (Tmax) of a single SC dose of icatibant was reported.
Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Maximum plasma concentration (Cmax) of a single SC dose of icatibant was reported.
Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Total plasma clearance (CL/F) of a single SC dose of icatibant was reported.
Area Under the Plasma Concentration-time Curve From Time Zero to 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, and 4 hours post-dose on Day 1
Area under the plasma concentration-time curve from time zero to 4 hours post-dose (AUC0-4) of a single SC dose of icatibant was reported.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of a single SC dose of icatibant was reported.
Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Volume of distribution (Vz/F) of a single SC dose of icatibant was reported.
Number of Participants Who Reported Presence of Anti-icatibant Antibodies
时间窗: Pre-dose up to 97 days post-dose
The number of participants who reported anti-icatibant antibodies were reported.
Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3
时间窗: 1 h post-dose up to 9 days post-dose
The number of participants with injection site reactions (erythema, swelling, burning sensation, itching/pruritus, warm sensation, cutaneous pain, or other) that occurred after subsequent icatibant administration by study-site personnel (health care practitioner \[HCP\] administration) or by caregiver/self (caregiver administration) was reported. In the below table, E-2 refers to icatibant exposure 2 and E-3 refers to icatibant exposure 3.
Number of Participants With Clinically Significant Changes in Reproductive Hormones
时间窗: Pre-dose up to 97 days post-dose
Reproductive hormone levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and progesterone in females, and FSH, LH, and testosterone in males were measured. The number of participants with clinically significant changes in reproductive hormones was reported.
Area Under the Plasma Concentration-time Curve From Time Zero to 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant
时间窗: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Area under the plasma concentration-time curve from time zero to 6 hours post-dose (AUC0-t) of a single SC dose of icatibant was reported.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations
时间窗: Pre-dose up to 97 days post-dose
Clinical laboratory evaluations included clinical chemistry (including liver function tests), hematology, urinalysis. The number of participants who reported clinically significant changes in clinical laboratory evaluations were reported.
次要结局
- Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1(From start of study drug administration up to 52 hours post-dose)
- Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3(From start of study drug administration up to 28 hours post-dose)
- Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores(From start of study drug administration up to 8.5 hours post-dose)
- Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3(From start of study drug administration up to 12 hours post-dose)
- Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1(From start of study drug administration up to 8.5 hours post-dose)
- Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3(From start of study drug administration up to 12 hours post-dose)
- Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1(From 2 hours post-dose to 4 hours post-dose)
- Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3(From 2 hours post-dose to 4 hours post-dose)
- Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1(From start of study drug administration up to 8.5 hours post-dose)
- Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1(From start of study drug administration up to 52 hours post-dose)
- Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3(From start of study drug administration up to 28 hours post-dose)
- Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores(From start of study drug administration up to 8.5 hours post-dose)
- Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration(From the start of study drug administration up to 52 hours post-dose)