A Study of Icatibant (TAK-667) in Japanese Children and Teenagers With Acute Attacks of Hereditary Angioedema
Condition: Hereditary Angioedema
MeSH terms: Angioedema; Angioedemas, Hereditary
Intervention: TAK-667
Intervention description: TAK-667 single SC administration
Intervention MeSH terms: Icatibant
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the investigator or subinvestigator, the participant's parent or
             legal guardian is capable of understanding and complying with protocol requirements.

          2. 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.

          3. The participant is in Japan and is Japanese; defined as born in Japan and having
             Japanese parents and Japanese maternal and paternal grandparents.

          4. 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.

          5. The participant weighs >=12 kg at the time of the current HAE attack.

          6. 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:

               1. Family history of angioedema

               2. Characteristic attack manifestations, recurrent attacks

               3. Functional complement 1 (C1) esterase inhibitor (C1-INH) deficiency

               4. 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).

          7. 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.

               1. 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

               2. 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).

          8. 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.

          9. The participant commences treatment within 12 hours after the onset of current HAE
             attack.

         10. 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.

        Exclusion Criteria:

          1. The participant will require an intervention to support the airway (eg, intubation,
             tracheotomy, cricothyrotomy) due to the current HAE attack.

          2. 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.

          3. The participant has a diagnosis of angioedema other than HAE

          4. 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).

          5. The participant has received treatment with any pain medication since the onset of the
             current HAE attack.

          6. 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.

          7. The participant has received treatment with ACE inhibitors within 7 days prior to
             treatment.

          8. The participant has used hormonal contraceptive within 90 days prior to treatment.

          9. The participant has received androgen or attenuated androgens (eg, danazol,
             testosterone) within 90 days prior to treatment.

         10. The participant has participated in another clinical study within the past 30 days
             before screening.

         11. 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.

         12. 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.

         13. The participant has a history of hypersensitivity or allergies to icatibant.

         14. The participant is judged by the investigator as being ineligible for any other
             reason; eg. a serious concomitant illness or condition.