Clinical trial NCT03888755: A Study of Icatibant for Acute Attacks of Hereditary Angioedema in Japanese Participants
Official title: An Open-Label Study of Icatibant in Japanese Subjects With Acute Attacks of Hereditary Angioedema.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy, pharmacokinetics (PK), and safety of icatibant for the treatment of acute attacks in Japanese participants with type I or type II hereditary angioedema (HAE).


Eligibility criteria: Inclusion Criteria:

1. The participant is in Japan and is Japanese; defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
2. The participant is male or female and greater than or equal to (\>=) 18 years of age at the time of informed consent.
3. The participant has a confirmed diagnosis of hereditary angioedema (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. C1 esterase inhibitor (C1-INH) deficiency
   4. In the absence of a family history of angioedema, exclusion of other forms of angioedema (example: acquired angioedema)
4. If the participant does not have a 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-NH test results which demonstrate a quantitative and/or 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 based on a normal level of C1q.
5. The current HAE attack must be in the cutaneous, abdominal, and/or laryngeal (inclusive of laryngeal and pharyngeal) areas.
6. The attack must be moderate to severe for non-laryngeal and mild to moderate for laryngeal as determined by investigator global assessment at pretreatment (baseline).
7. The participant commences treatment within 6 hours of the attack becoming at least mild (laryngeal) or moderate (non-laryngeal) in severity, but not more than 12 hours (h) after the onset of the attack. Note: for participant who present to the hospital/clinic with symptoms which have already progressed to at least moderate (non-laryngeal) or mild (laryngeal) severity, their duration can be estimated by the investigator through questioning of the participant.
8. The participant (or the participant's parent/legal guardian, if applicable) has provided written informed consent which has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).

   1. 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. OR
   2. If the participant is a minor (that is \[i.e.\] \< 20 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.
9. Females of childbearing potential must have a negative urine pregnancy test and must use medically acceptable methods to prevent pregnancy during their active participation in the study, (time from icatibant treatment of the acute attack to the follow-up visit at Day 7 \[+3 days\]), with the exception of those females who have had a total hysterectomy or bilateral oophorectomy, or who are 2 years post menopausal.

Exclusion Criteria:

1. The participant will require an intervention to support the airway (example: intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema.
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 in conjunction with the investigator global assessment 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 (non-hereditary angioedema, example: acquired angioedema).
4. The participant has received previous treatment with icatibant.
5. The participant is enrolled in another clinical study that involves investigation or use of any investigational product (drug or device) within 30 days prior to study enrollment or at any time during the study.
6. The participant has received treatment with any pain medication since the onset of the current angioedema attack.
7. The participant has received replacement therapy (C1-INH products, fresh frozen plasma \[FFP\]) \< 5 days (120 hours) from the onset of the current angioedema attack.
8. The participant is receiving treatment with angiotensin converting enzyme (ACE) inhibitors.
9. The participant has evidence of coronary artery disease based on medical history at the screening examination or at pretreatment; example: unstable angina pectoris or severe coronary heart disease and 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).
10. The participant has a serious pre-existing condition or condition that, in the opinion of the investigator, would be a contraindication for participation in the trial.
11. The participant is pregnant or breastfeeding.
12. The participant 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.

Primary outcomes:
measure: Time to Onset of Symptom Relief (TOSR)
timeFrame: Baseline up to 120 hours post-treatment
Secondary outcomes:
measure: Time to Onset of Primary Symptom Relief (TOSR-P)
timeFrame: Baseline up to 120 hours post-treatment
measure: Change From Baseline in the Composite Visual Analog Scale (VAS) Score
timeFrame: Baseline, 2, 4 and 8 hours post-treatment
measure: Composite Symptom Score (SS) Assessed by Investigator
timeFrame: 8 hours post dose
measure: Composite Symptom Score (SS) Assessed by Participant
timeFrame: 8 hours post dose
measure: Investigator Global Assessment
timeFrame: 2, 4 and 8 hours post dose
measure: Time to Initial Symptom Improvement by Investigator
timeFrame: Baseline up to 120 hours post-treatment
measure: Time to Initial Symptom Improvement by Participants
timeFrame: Baseline up to 120 hours post-treatment
measure: Time to Almost Complete Symptom Relief As Assessed by Visual Analog Scale (VAS) Score
timeFrame: Baseline up to 120 hours post-treatment
measure: Maximum Observed Plasma Concentration (Cmax) of Icatibant After a Single Subcutaneous (SC) Administration of Icatibant
timeFrame: Baseline, 0.75, 2 hours post-treatment
measure: Area Under the Concentration-time Curve From 0 to 2 Hours (AUC0-2) After a Single Subcutaneous (SC) Administration of Icatibant
timeFrame: Baseline, 0.75, 2 hours post-treatment
measure: Area Under the Concentration-time Curve From 0 to 4 Hours (AUC0-4) After a Single Subcutaneous (SC) Administration of Icatibant
timeFrame: Baseline, 0.75, 2 hours post-treatment
measure: Area Under the Concentration-time Curve From 0 to 6 Hours (AUC0-6) After a Single Subcutaneous (SC) Administration of Icatibant
timeFrame: Baseline, 0.75, 2 hours post-treatment
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration to follow-up (up to 10 days)
measure: Number of Participants With Injection Site Reactions Reported as Adverse Event (AE)
timeFrame: From start of study drug administration to follow-up (up to 10 days)
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Tests Reported as Adverse Event (AE)
timeFrame: From start of study drug administration to follow-up (up to 10 days)
measure: Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Event (AE)
timeFrame: From start of study drug administration to follow-up (up to 10 days)
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as Adverse Event (AE)
timeFrame: From start of study drug administration to follow-up (up to 10 days)
Other outcomes:
Locations:
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kobe
country: Japan
facility: Kobe University Hospital
city: Kumamoto
country: Japan
facility: Saiseikai Kumamoto Hospital
city: Niigata
country: Japan
facility: Niigata City General Hospital
city: Tokyo
country: Japan
facility: Nihon University Itabashi Hospital
city: Tomakomai
country: Japan
facility: Tomakomai City Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: