A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema
HGT-FIR-086 is a multicenter, open-label, non-randomized, single-arm study to evaluate the Pharmacokinetics, tolerability, and safety including effect 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.
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- Pharmacokinetic (PK) Profile after a single SC injection (in prepubertal children with an acute attack of HAE and pubertal/postpubertal children with or without an acute attack of HAE) [ Time Frame: Administration through 6 hours ] [ Designated as safety issue: No ]PK parameter estimates will include, where appropriate: actual icatibant and metabolite concentrations at each sampling time, time to peak concentration (Tmax), actual peak (Cmax) and minimum (Cmin) concentrations, clearance (CL/F), actual area under the plasma concentration-time-curve (AUC0-last and AUC0-inf), mean residence time (MRT), volume of distribution at steady state (Vss/F) and elimination half-life (t1/2).
- Safety of a single SC dose of icatibant [ Time Frame: Treatment through day 90 ] [ Designated as safety issue: Yes ]Safety and tolerability will be assessed by standard criteria including injection site reactions, adverse events, vital signs, ECG recordings, physical examination, clinical laboratory parameters (serum chemistry [including liver function tests], hematology, urinalysis), reproductive hormone levels, and immunogenicity (presence of anti-icatibant antibodies).
- Time to onset of relief of symptoms and time to minimal symptoms, as measured by investigator- and subject-reported outcomes for subjects who have experienced HAE attack only [ Time Frame: Treatment through 8 hours ] [ Designated as safety issue: No ]
- For subjects 2 to less than 18 years of age: investigator assessment and scoring of cutaneous, abdominal and laryngeal symptoms of acute HAE attacks by an investigator-rated symptom score.
- For subjects 4 years of age and older: subject self-assessment of HAE related pain using the Faces Pain Scale-Revised (FPS-R).
- For subjects less than 4 years of age: investigator assessment of HAE-related pain (cutaneous, abdominal and laryngeal) using a validated pain scale (Faces, Legs, Activity, Cry, and Consolability [FLACC]).
- Proportion of subjects with worsened intensity of clinical HAE symptoms between 2 and 4 hours after treatment with icatibant for subjects who have experienced HAE attack only [ Time Frame: Treatment through 4 hours ] [ Designated as safety issue: No ]
- Incidence of rescue medication use for subjects who have experienced HAE attack only [ Time Frame: Treatment through day 90 ] [ Designated as safety issue: No ]
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
Other Name: Firazyr
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01386658
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|Study Director:||Alan Kimura, M.D.||Shire Human Genetic Therapies, Inc.|