A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema

NCT01386658 | Completed Phase 3 Results

• 2 other identifiers: HGT-FIR-0862011-003825-81
• Study Type: interventional
• Target: 32
• Locations: 9 countries
• Sites: 25

Brief Summary

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.

Conditions

Hereditary Angioedema (HAE)

Keywords

Efficacy; Hereditary angioedema; HAE; Pediatric; Children; Pharmacokinetics; Safety; Firazyr; icatibant

Outcome Measures

Primary Outcomes (16)

• Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant

  Time to peak concentration (Tmax) of a single SC dose of icatibant was reported.

  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 Subcutaneous (SC) Dose of Icatibant

  Maximum plasma concentration (Cmax) of a single SC dose of icatibant was reported.

  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 Subcutaneous (SC) Dose of Icatibant

  Total plasma clearance (CL/F) of a single SC dose of icatibant was reported.

  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 4 Hours Post-dose (AUC0-4) of a Single Subcutaneous (SC) Dose of Icatibant

  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.

  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 6 Hours Post-dose (AUC0-t) of a Single Subcutaneous (SC) Dose of Icatibant

  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.

  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 Subcutaneous (SC) Dose of Icatibant

  Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) of a single SC dose of icatibant was reported.

  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 Subcutaneous (SC) Dose of Icatibant

  Volume of distribution (Vz/F) of a single SC dose of icatibant was reported.

  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 Subcutaneous (SC) Dose of Icatibant

  Elimination half-life (t1/2) of a single SC dose of icatibant was reported.

  Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1

• Number of Participants With Clinically Significant Changes in Vital Signs

  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.

  Pre-dose up to 97 days post-dose

• Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)

  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.

  6 - 8 hours post-dose on Day 1

• Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations

  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.

  Pre-dose up to 97 days post-dose

• Number of Participants Who Reported Presence of Anti-icatibant Antibodies

  The number of participants who reported anti-icatibant antibodies were reported.

  Pre-dose up to 97 days post-dose

• Number of Participants With Adverse Events (AEs)

  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.

  From the start of study drug administration up to 97 days post-dose

• Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1

  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.

  1 h post-dose on Day 1 up to 9 days post-dose

• Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3

  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.

  1 h post-dose up to 9 days post-dose

• Number of Participants With Clinically Significant Changes in Reproductive Hormones

  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.

  Pre-dose up to 97 days post-dose

Secondary Outcomes (13)

• 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

• 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

Study Arms (1)

Icatibant

EXPERIMENTAL

Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg

Drug: icatibant

Interventions

icatibant DRUG

Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg

Also known as: Firazyr

Icatibant

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (26)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Breathe America

Shreveport, Louisiana, 71106, United States

Location

Institute for Asthma and Allergy, PC

Chevy Chase, Maryland, 20815, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63141, United States

Location

Bernstein Clinical Research Center, LLC

Cincinnati, Ohio, 45231, United States

Location

Toledo Institute of Clinical Research

Toledo, Ohio, 43617, United States

Location

Oklahoma Institute of Allergy and Asthma Clinical Research, LLC

Oklahoma City, Oklahoma, 73131, United States

Location

Allergy Asthma Dermatology Research Center

Lake Oswego, Oregon, 97035, United States

Location

Penn State University

Hershey, Pennsylvania, 17033, United States

Location

AARA Research Center

Dallas, Texas, 75231, United States

Location

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Medizinische Universität Graz Hautklinik

Graz, 8036, Austria

Location

McMaster University

Hamilton, Ontario, L8S 4K1, Canada

Location

Hospital Infantil Universitario de San Jose

Bogota, Cundinamarca, Colombia

Location

Klinikum der Johann Wolfgang Goethe University

Frankfurt, 60590, Germany

Location

Johannes-Gutenberg University Clinical Research Center

Mainz, 55131, Germany

Location

HZRM Hämophilie Zentrum Rhein Main GmbH

Walldorf, 64546, Germany

Location

Heim Pal Childrens Hospital

Budapest, H-1131, Hungary

Location

Bnai Zion Medical Center, Allergy and Immunology Institute

Haifa, Israel

Location

Tel Aviv Sourasky Medical Center, Pulmonology and Allergy Unit

Tel Aviv, 64239, Israel

Location

Sheba Medical Center Allergy and Immunology Angioedema Center

Tel Litwinsky, 52621, Israel

Location

University of Naples Federico II, Dipartimento di Medicina Interna

Naples, 80131, Italy

Location

Unidad de Alergia, Edif. Consultas Externas, Planta Baja HOSPITAL UNIVERSITARIO LA PAZ

Madrid, 28046, Spain

Location

University Hospital, Pediatric Pulmonology and Allergy Unit

Valencia, 46026, Spain

Location

Related Publications (1)

• Farkas H, Reshef A, Aberer W, Caballero T, McCarthy L, Hao J, Nothaft W, Schranz J, Bernstein JA, Li HH. Treatment Effect and Safety of Icatibant in Pediatric Patients with Hereditary Angioedema. J Allergy Clin Immunol Pract. 2017 Nov-Dec;5(6):1671-1678.e2. doi: 10.1016/j.jaip.2017.04.010. Epub 2017 Jun 7.

  PMID: 28601641 DERIVED

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: June 28, 2011
• First Posted: July 1, 2011
• Study Start: January 27, 2012
• Primary Completion: March 12, 2018
• Study Completion: March 12, 2018
• Last Updated: June 8, 2021
• Results First Posted: March 25, 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

HU (1); DE (3); AU (1); IL (3); IT (1); CA (1); CO (1); US (12); ES (2)