Clinical trial NCT01386658: A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema
Official title: A Multicenter, Open-Label, Non-Randomized Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Administration of Icatibant in Children and Adolescents With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Keywords: Efficacy
Hereditary angioedema
HAE
Pediatric
Children
Pharmacokinetics
Safety
Firazyr
icatibant
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-07-01
Enrollment: 32
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Study HGT-FIR-086 will enroll 30 subjects from 2 to less than 18 years of age, divided into 2 groups: prepubertal and pubertal/postpubertal. At least 10 prepubertal children and at least 20 adolescents (including 10 treated during a HAE attack) must be enrolled in the study.

After a qualifying screening period, the PK, safety/tolerability, and efficacy of treatment with SC icatibant will be evaluated in at least 20 subjects (10 prepubertal and 10 pubertal/postpubertal subjects) who present with cutaneous, abdominal, or laryngeal symptoms of an acute attack of HAE. The PK and safety/tolerability of SC icatibant will be evaluated in at least 10 additional pubertal/postpubertal subjects who meet screening criteria and receive treatment with SC icatibant in the absence of a current acute HAE attack.

The planned duration of active participation for subjects who present with an initial attack of acute HAE will consist of treatment with a single subcutaneous injection of icatibant on Day 1 through follow up at day 90.

After having received initial treatment with icatibant, either during or in the absence of an attack, at least 10 pubertal/postpubertal subjects who subsequently experience an acute HAE attack may continue to receive treatment with icatibant as a single SC administration per attack for a total of 3 eligible icatibant-treated attacks.

The period of active participation in the study for prepubertal subjects will be approximately 90 days, while that for pubertal/postpubertal subjects could be a maximum of approximately 270 or 360 days (3 separate active periods of approximately 90 days for those treated with icatibant during an attack; 4 separate active periods for those treated without an attack), with each active period separated by periods of inactive participation of variable duration.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Documented diagnosis of HAE Type I or II.
3. Informed consent (and subject assent as appropriate) signed by the subject's parent(s)or legal guardian(s).

Exclusion Criteria:

1. Diagnosis of angioedema other than HAE.
2. 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.
3. Any known factor/disease that might interfere with the treatment compliance, study conduct,or result interpretation.
4. Congenital or acquired cardiac anomalies that interfere significantly with cardiac function.
5. Treatment with ACE inhibitors within 7 days prior to treatment.
6. Use of hormonal contraception within the 90 days prior to treatment.
7. Androgen use (eg, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within the 90 days prior to treatment.
8. Pregnancy or breastfeeding.
9. A physical condition that interferes with pubertal status determination.

Primary outcomes:
measure: Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: 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
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, and 4 hours post-dose on Day 1
measure: 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
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant
timeFrame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Pre-dose up to 97 days post-dose
measure: Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)
timeFrame: 6 - 8 hours post-dose on Day 1
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations
timeFrame: Pre-dose up to 97 days post-dose
measure: Number of Participants Who Reported Presence of Anti-icatibant Antibodies
timeFrame: Pre-dose up to 97 days post-dose
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From the start of study drug administration up to 97 days post-dose
measure: Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1
timeFrame: 1 h post-dose on Day 1 up to 9 days post-dose
measure: Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3
timeFrame: 1 h post-dose up to 9 days post-dose
measure: Number of Participants With Clinically Significant Changes in Reproductive Hormones
timeFrame: Pre-dose up to 97 days post-dose
Secondary outcomes:
measure: Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
timeFrame: From start of study drug administration up to 8.5 hours post-dose
measure: Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
timeFrame: From start of study drug administration up to 12 hours post-dose
measure: Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
timeFrame: From start of study drug administration up to 52 hours post-dose
measure: Time to Onset of Symptom Relief (TOSR) for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
timeFrame: From start of study drug administration up to 28 hours post-dose
measure: Time to Onset of Symptom Relief (TOSR) for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
timeFrame: From start of study drug administration up to 8.5 hours post-dose
measure: Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
timeFrame: From start of study drug administration up to 8.5 hours post-dose
measure: Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
timeFrame: From start of study drug administration up to 12 hours post-dose
measure: Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
timeFrame: From start of study drug administration up to 52 hours post-dose
measure: Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
timeFrame: From start of study drug administration up to 28 hours post-dose
measure: Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
timeFrame: From start of study drug administration up to 8.5 hours post-dose
measure: Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration
timeFrame: From the start of study drug administration up to 52 hours post-dose
measure: Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1
timeFrame: From 2 hours post-dose to 4 hours post-dose
measure: Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 2 and 3
timeFrame: From 2 hours post-dose to 4 hours post-dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Shreveport
country: United States
facility: Breathe America
state: Louisiana
city: Chevy Chase
country: United States
facility: Institute for Asthma and Allergy, PC
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center, LLC
state: Ohio
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Institute of Allergy and Asthma Clinical Research, LLC
state: Oklahoma
city: Lake Oswego
country: United States
facility: Allergy Asthma Dermatology Research Center
state: Oregon
city: Hershey
country: United States
facility: Penn State University
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Campbelltown
country: Australia
facility: Campbelltown Hospital
state: New South Wales
city: Graz
country: Austria
facility: Medizinische Universität Graz Hautklinik
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Bogota
country: Colombia
facility: Hospital Infantil Universitario de San Jose
state: Cundinamarca
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe University
city: Mainz
country: Germany
facility: Johannes-Gutenberg University Clinical Research Center
city: Walldorf
country: Germany
facility: HZRM Hämophilie Zentrum Rhein Main GmbH
city: Budapest
country: Hungary
facility: Heim Pal Childrens Hospital
city: Haifa
country: Israel
facility: Bnai Zion Medical Center, Allergy and Immunology Institute
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center, Pulmonology and Allergy Unit
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center Allergy and Immunology Angioedema Center
city: Naples
country: Italy
facility: University of Naples Federico II, Dipartimento di Medicina Interna
city: Madrid
country: Spain
facility: Unidad de Alergia, Edif. Consultas Externas, Planta Baja HOSPITAL UNIVERSITARIO LA PAZ
city: Valencia
country: Spain
facility: University Hospital, Pediatric Pulmonology and Allergy Unit
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.