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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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 Summary:

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 perio
Sponsor: Shire

Current Primary Outcome:

• 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 ]
  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 ]
  Safety and tolerability will be assessed by standard criteria including injection site reactions, adverse events, vital signs, electrocardiogram (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).

Original Primary Outcome:

• Pharmacokinetic Profile after a single SC injection [ Time Frame: Administration through 48 hours ]
  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 ]
  Safety will be assessed by standard criteria including physical examination, vital signs,clinical laboratory evaluations (clinical chemistry [including liver function tests],hematology, urinalysis), and immunogenicity (presence of anti-icatibant antibodies),recording of concomitant medications, and monitoring of AEs. Local tolerability will be assessed by evaluation of reactions at the site of study drug administration (injection site).

Current Secondary Outcome:

• Time to onset of relief of symptoms and time to minimal symptoms, as measured byinvestigator- and subject-reported outcomes (only for subjects treated with icatibant during a HAE attack) [ Time Frame: Treatment through 8 hours ]
  • 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 only: subject self-assessment of HAE related pain using the Faces Pain Scale-Revised (FPS-R).• For subjects less than 4 years of age only: 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 ]
• Incidence of rescue medication use for subjects who have experienced HAE attack only [ Time Frame: Treatment through day 90 ]
  Rescue medications are only monitored through the current attack and not through 90 days

Original Secondary Outcome:

• Efficacy of a single SC dose of icatibant [ Time Frame: Treatment through 8 hours ]
  Efficacy will be assessed using both investigator- and subject-reported outcomes,depending on the subject's age. Investigators will assess and score symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE for all subjects using an investigator-rated symptom score. Subjects who are 4 years of age or older will perform a self-assessment using the Faces Pain Scale-Revised (FPS-R). Subjects who are below 4 years of age will have symptoms assessed by the investigator only. The time of initial symptom relief as assessed by the investigator will be recorded for all subjects.
• Levels of reproductive hormones after single SC dose of icatibant [ Time Frame: Treatment through 6 hours ]
  Levels of reproductive hormones will be assessed in female (FSH, LH, estradiol, progesterone)and male (FSH, LH, and testosterone)subjects.

Dates:
Date Received: June 28, 2011
Date Started: November 2011
Date Completion: December 2017
Last Updated: February 6, 2017
Last Verified: February 2017