A Study of Icatibant for Acute Attacks of Hereditary Angioedema in Japanese Participants

NCT03888755 | Completed Phase 3 Results

• 1 other identifier: SHP-FIR-301
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 8

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).

Conditions

Hereditary Angioedema (HAE)

Outcome Measures

Primary Outcomes (1)

• Time to Onset of Symptom Relief (TOSR)

  The TOSR was defined as a 50 percent (%) reduction from the pre-treatment score in the 3-symptom composite VAS score for non-laryngeal attacks and 5-symptom composite VAS score for laryngeal attacks. A VAS utilizes a scale consisting of a 100 millimeter (mm) horizontal line with extreme values at the beginning (0 mm = no symptom) and end (100 mm = worst possible symptom) of the line. The participant should draw a vertical line at the point along the scale that represents the current status of the measured symptom. Composite VAS scores were calculated as the average of VAS measurements for skin swelling, skin pain, and abdominal pain (3-symptom composite) for non-laryngeal attacks and for skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change (5-symptom composite) for laryngeal attacks.

  Baseline up to 120 hours post-treatment

Secondary Outcomes (17)

• Time to Onset of Primary Symptom Relief (TOSR-P)

  Baseline up to 120 hours post-treatment

• Change From Baseline in the Composite Visual Analog Scale (VAS) Score

  Baseline, 2, 4 and 8 hours post-treatment

• Composite Symptom Score (SS) Assessed by Investigator

  8 hours post dose

• Composite Symptom Score (SS) Assessed by Participant

  8 hours post dose

• Investigator Global Assessment

  2, 4 and 8 hours post dose

Study Arms (1)

Icatibant

EXPERIMENTAL

Participants with 1 acute non-laryngeal or laryngeal attack will receive a single icatibant 30 milligram (mg) subcutaneous (SC) injection in the abdominal area. A maximum of 3 SC injections (or 90 mg) of icatibant that are at least 6 hours apart can be given for treatment of an attack if, within 48 hours of the initial treatment, there is insufficient relief or worsening of symptoms.

Drug: Icatibant

Interventions

Icatibant DRUG

Participants will receive icatibant 30 mg SC injection in the abdominal area.

Icatibant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 greater than or equal to (\>=) 18 years of age at the time of informed consent.
• 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:
• Family history of angioedema
• Characteristic attack manifestations, recurrent attacks
• C1 esterase inhibitor (C1-INH) deficiency
• 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.
• 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
• The current HAE attack must be in the cutaneous, abdominal, and/or laryngeal (inclusive of laryngeal and pharyngeal) areas.
• 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).
• 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.
• 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).
• 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
• 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.
• 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.

You may not qualify if:

• The participant will require an intervention to support the airway (example: intubation, tracheotomy, cricothyrotomy) due to the current attack of angioedema.
• 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.
• The participant has a diagnosis of angioedema other than HAE (non-hereditary angioedema, example: acquired angioedema).
• The participant has received previous treatment with icatibant.
• 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.
• The participant has received treatment with any pain medication since the onset of the current angioedema attack.
• 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.
• The participant is receiving treatment with angiotensin converting enzyme (ACE) inhibitors.
• 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).
• 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.
• The participant is pregnant or breastfeeding.
• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (8)

Fukushima Medical University Hospital

Fukushima, Japan

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Kobe University Hospital

Kobe, Japan

Location

Saiseikai Kumamoto Hospital

Kumamoto, Japan

Location

Niigata City General Hospital

Niigata, Japan

Location

Nihon University Itabashi Hospital

Tokyo, Japan

Location

Tomakomai City Hospital

Tomakomai, Japan

Location

Yokohama City University Hospital

Yokohama, Japan

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

icatibant

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 25, 2019
• Study Start: March 18, 2015
• Primary Completion: February 12, 2016
• Study Completion: February 12, 2016
• Last Updated: June 3, 2021
• Results First Posted: August 8, 2019

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (8)