A Multicenter, Open-Label, Non-randomized Phase 3 Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneous Administration of Icatibant (TAK-667) in Japanese Children and Adolescents With Acute Attacks of Hereditary Angioedema
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2
- 试验地点
- 3
- 主要终点
- Number of Participants With Injection Site Reactions
研究概览
简要总结
The main aim of the study is to check for side effects from icatibant in children and teenagers with hereditary angioedema (HAE). Other aims are to check how well icatibant controls HAE symptoms in these children and teenagers, and how much icatibant stays in their blood.
At the first visit, the study doctor will check if each child or teenager can take part. For those who can take part, participants and their parents or caregivers will visit the clinic or hospital when they have their next HAE attack. Participants will receive 1 injection (shot) of icatibant in a vein and will stay at the clinic or hospital until their HAE symptoms are under control. Participants can receive up to 2 more injections of icatibant over time if their HAE symptoms don't improve or get worse.
After the participants go home, the study staff will follow up with them by a telephone call 1 to 2 days later. Then, the participants will visit the clinic or hospital 1 week after they received the icatabant injection.
The participant can visit the clinic or hospital and be treated with icatibant in the same way for up to 3 HAE attacks in total.
详细描述
The drug being tested in this study is called TAK-667. TAK-667 is being tested to treat Japanese Children and Adolescents who experience acute attack of HAE. This study will look at safety, efficacy and pharmacokinetics (PK) of people who take TAK-667.
The study will enroll at least up to 3 participants. Participants will take TAK-667 with SC administration on the abdomen. The dose of TAK-667 will be dependent on the participant's body weight (Up to 30 mg; 10 mg for 12 kg to 25 kg, 15 mg for 26 kg to 40 kg, 20 mg for 41 kg to 50kg, 25 mg for 51 kg to 65 kg, 30 mg for >65 kg).
This multi-center trial will be conducted in Japan. The overall time to participate in this study is 25 days as a maximum (screening day for initial attack plus 8 days post dose for each 3 attacks as a maximum). Participants will make multiple visits to the clinic and will be closely monitored in the hospital/study center for at least 8 hours after administration and receive physical examination and assessment to evaluate safety, efficacy and PK. Hospitalization may be prolonged until, in the opinion of the investigator, the participant is clinically stable and onset of HAE attack is completely resolved.
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
- •In the opinion of the investigator or subinvestigator, the participant's parent or legal guardian is capable of understanding and complying with protocol requirements.
- •The participant's parent or the participant's legal guardian is capable of signing and dating a written informed consent form on behalf of the participant prior to the initiation of any study procedures. Written informed assent is also obtained from the participant as much as possible.
- •The participant is in Japan and is Japanese; defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
- •The participant is male or female and 2 to <18 years of age (ie, from the second birthday through the day prior to the eighteenth birthday) at the time of informed consent.
- •The participant weighs >=12 kg at the time of the current HAE attack.
- •The participant who has a documented and confirmed diagnosis of HAE type I or II. Diagnosis may be based on historical data using the following criteria:
- •Family history of angioedema
- •Characteristic attack manifestations, recurrent attacks
- •Functional complement 1 (C1) esterase inhibitor (C1-INH) deficiency
- •In the absence of a family history of angioedema, exclusion of other forms of angioedema (eg. angiotensin converting enzyme (ACE)-induced angioedema, allergic angioedema) based on medical judgement (eg, concomitant medication, response to antihistamines or glucocorticoids, information of genetic mutation).
- •If the participant does not have a documented and confirmed diagnosis of HAE type I or II based on historical data, including C1-INH deficiency, the participant's diagnosis must be determined prior to treatment by C1-INH test results which demonstrate a functional C1-INH deficiency.
- •HAE type I: Low amount of C1-INH protein and low level of C1-INH activity; HAE type II: Normal or increased amount of C1-INH protein and low level of C1-INH activity
- •In the absence of a family history of angioedema, exclusion of other forms of angioedema (eg. ACE-induced angioedema, allergic angioedema) based on medical judgement (eg, concomitant medication, response to antihistamines or glucocorticoids, information of genetic mutation).
- •The current HAE attack must be in the cutaneous, abdominal, and/or laryngeal (inclusive of laryngeal and pharyngeal) areas, but no prespecified attack severity criteria are required for treatment.
- •The participant commences treatment within 12 hours after the onset of current HAE attack.
- •A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study, and proves negative in the pregnancy test at screening.
排除标准
- •The participant will require an intervention to support the airway (eg, intubation, tracheotomy, cricothyrotomy) due to the current HAE attack.
- •The participant presents with an HAE attack with laryngeal/upper respiratory tract symptoms which are considered severe in the investigator's clinical judgment and which may necessitate urgent care and/or impede the conduct of study efficacy assessments.
- •The participant has a diagnosis of angioedema other than HAE
- •The participant has evidence of stroke or coronary artery disease based on medical history at the screening examination or at pretreatment; eg, acute ischemic heart disease, unstable angina pectoris, severe coronary heart disease or congestive heart failure, that in the investigator's judgment would be a contraindication for participation in the trial (New York Heart Association [NYHA] class 3 and 4).
- •The participant has received treatment with any pain medication since the onset of the current HAE attack.
- •The participant has received replacement therapy (C1-INH products, fresh frozen plasma [FFP]) within 5 days (120 hours) from the onset of the current HAE attack.
- •The participant has received treatment with ACE inhibitors within 7 days prior to treatment.
- •The participant has used hormonal contraceptive within 90 days prior to treatment.
- •The participant has received androgen or attenuated androgens (eg, danazol, testosterone) within 90 days prior to treatment.
- •The participant has participated in another clinical study within the past 30 days before screening.
- •The participant, the participant's parent, or legal guardian is unable to understand the nature, scope, and possible consequences of the protocol, or is unlikely to comply with the protocol assessments, unable to return for follow up visits, or unlikely to complete the study for any reason.
- •If female, the participant is pregnant or lactating or intending to become pregnant before participating in this study, during the study, and within 30 days after last dose of the icatibant.
- •The participant has a history of hypersensitivity or allergies to icatibant.
- •The participant is judged by the investigator as being ineligible for any other reason; eg. a serious concomitant illness or condition.
研究组 & 干预措施
TAK-667
TAK-667, single SC administration on the abdomen on Day 1. The dose of TAK-667 will be dependent on the participant's body weight (Up to 30 mg; 10 mg for 12 kg to 25 kg, 15 mg for 26 kg to 40 kg, 20 mg for 41 kg to 50kg, 25 mg for 51 kg to 65 kg, 30 mg for >65 kg).
干预措施: TAK-667 (Drug)
结局指标
主要结局
Number of Participants With Injection Site Reactions
时间窗: Postdose, up to Day 8
Injection sites were examined for erythema, swelling, cutaneous pain, burning sensation, itching/pruritus, and warm sensation. Data for injection site reactions were collected separately from general reports of AEs. As pre-defined in the protocol, an injection site reaction not meeting SAE criteria was not required to be reported additionally as an AE.
Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Events (TEAE)
时间窗: Up to approximately 6 months
An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. A treatment-emergent adverse event (TEAE) was defined as any adverse event occurring after the start of Icatibant administration of the treatment period.
次要结局
- Plasma Concentration for TAK-667(Day 1 pre-dose and at multiple timepoints post-dose)
- Number of Participants Who Experienced at Least One TEAE Related to Resting 12-lead Electrocardiogram(Up to approximately 6 months)
- Number of Participants Who Experienced at Least One TEAE Related to Clinical Laboratory Parameters(Up to approximately 6 months)
- Number of Participants Who Experienced at Least One TEAE Related to Vital Sign(Up to approximately 6 months)
- Number of Participants Who Experience at Least One TEAE Related to Clinically Significant Changes in Reproductive Hormones(Up to approximately 6 months)
- Number of Participants Who Were Treated With Rescue Medication During Study(Up to approximately 6 months)
- Number of Participants Who Reported Presence of Anti-icatibant Antibodies(Up to approximately 6 months)
- Time to Onset of Symptom Relief With Faces Pain Scale-Revised (FPS-R) Scores for Participants of 4 Years Age and Older(Baseline, and post dose on Day 1)
- Time to Initial Symptom Improvement Reported by Investigator(Up to 8 hours post dose (or till the onset of HAE attacks were resolved))
- Time to Onset of Symptom Relief With Investigator-Rated Symptom Scores Assessed by Investigator(Baseline, and post dose on Day 1)
- Time to Onset of Symptom Relief by Faces, Legs, Activity, Cry, and Consolability (FLACC) Scale Assessed by Investigator for Participants of Younger Than 4 Years Age(Baseline, and post dose on Day 1)
- Number of Participants With Worsened Intensity of Clinical HAE Symptoms Between 2 and 4 Hours After Treatment With SC Icatibant Using Investigator-Rated Symptom Scores(From 2 hours post-dose to 4 hours post-dose)
- Time to Initial Symptom Improvement Reported by Participant(Up to 8 hours post dose (or till the onset of HAE attacks were resolved))
- Plasma Concentration for TAK-667 Metabolite M-I(Day 1 pre-dose and at multiple timepoints post-dose)
- Plasma Concentration for TAK-667 Metabolite M-II(Day 1 pre-dose and at multiple timepoints post-dose)