Hereditary Angioedema (HAE)Phase 3NCT01386658
A Pharmacokinetic, Tolerability and Safety Study of Icatibant in Children and Adolescents With Hereditary Angioedema
A Phase 3 study testing icatibant in people with Hereditary Angioedema (HAE), run by Shire at 26 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Hereditary Angioedema (HAE)
- What is being tested?
- icatibant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 26 sitesin 10 countries
- Study dates
- 27 Jan 2012to 12 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
26 sites in 10 countries.
26 sites in 10 countries
United States12 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Institute for Asthma and Allergy, PC
Chevy Chase, Maryland, 20815
Bernstein Clinical Research Center, LLC
Cincinnati, Ohio, 45231
AARA Research Center
Dallas, Texas, 75231
Penn State University
Hershey, Pennsylvania, 17033
Allergy Asthma Dermatology Research Center
Lake Oswego, Oregon, 97035
Children's Hospital Los Angeles
Los Angeles, California, 90027
Oklahoma Institute of Allergy and Asthma Clinical Research, LLC
Oklahoma City, Oklahoma, 73131
Breathe America
Shreveport, Louisiana, 71106
Washington University School of Medicine
St Louis, Missouri, 63141
University of South Florida
Tampa, Florida, 33613
Toledo Institute of Clinical Research
Toledo, Ohio, 43617
Germany3 sites
Klinikum der Johann Wolfgang Goethe University
Frankfurt, 60590
Johannes-Gutenberg University Clinical Research Center
Mainz, 55131
HZRM Hämophilie Zentrum Rhein Main GmbH
Walldorf, 64546
Israel3 sites
Bnai Zion Medical Center, Allergy and Immunology Institute
Haifa
Tel Aviv Sourasky Medical Center, Pulmonology and Allergy Unit
Tel Aviv, 64239
Sheba Medical Center Allergy and Immunology Angioedema Center
Tel HaShomer, 52621
Spain2 sites
Unidad de Alergia, Edif. Consultas Externas, Planta Baja HOSPITAL UNIVERSITARIO LA PAZ
Madrid, 28046
University Hospital, Pediatric Pulmonology and Allergy Unit
Valencia, 46026
Colombia1 site
Hospital Infantil Universitario de San Jose
Bogota, Cundinamarca
Italy1 site
University of Naples Federico II, Dipartimento di Medicina Interna
Naples, 80131
About this study
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
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.
Read the 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.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- icatibant
- Keywords
- Efficacy, Hereditary angioedema, HAE, Pediatric, Children, Pharmacokinetics, Safety, Firazyr, icatibant
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
icatibantDrug
Also called Firazyr
Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg
| Study group | Role | What they receive |
|---|---|---|
| Icatibant | Experimental | Single dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg Receives: Drug: icatibant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20 percent (%) improvement in the average post-treatment symptom score with no worsening of any single component score for the initial icatibant exposure. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of hereditary angioedema (HAE) using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received initial icatibant administration was reported.
Measured: 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
The TOSR was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which there was at least a 20% improvement in the composite (or average) post-treatment symptom score with no worsening of any single component score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Measured: 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
The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received initial icatibant administration was reported.
Measured: 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
The TOSR was defined as the earliest time at which the post-treatment score improved by at least one level. Participants of 4 years age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). TOSR for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Measured: 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
The TOSR was defined as the earliest time at which a 20% improvement was seen in the total post-treatment score. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. Face(F): 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); Legs(L): 0 (normal position/relaxed) - 2 (kicking/legs drawn up); Activity(A): 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); Cry(C): 0 (No cry [awake/asleep]) - 2 (crying steadily/screams/sobs or frequent complaints); Consolability(C): 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10.
Measured: From start of study drug administration up to 8.5 hours post-dose
Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received initial icatibant administration was reported.
Measured: From start of study drug administration up to 8.5 hours post-dose
Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
Time to minimum symptom was defined as the duration of time in hours from study drug administration to the earliest time post-treatment at which all symptoms were either mild or absent for the investigator-reported symptom score. The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5-point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Measured: From start of study drug administration up to 12 hours post-dose
Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received initial icatibant administration was reported.
Measured: From start of study drug administration up to 52 hours post-dose
Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which post-treatment score improved to zero (or no pain). Participants of 4 years of age and older self-assessed their HAE-related pain using the FPS-R instrument. FPS-R is a self-reported measure used to assess the intensity of children's pain and it is scored using a 0 to 10 scale (0=no pain to 10=very much pain). Time to minimum symptom for participants who received subsequent icatibant administration by HCP administration or by caregiver/ self-administration was reported.
Measured: From start of study drug administration up to 28 hours post-dose
Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
Time to minimum symptoms was defined as the duration of time in hours from study drug administration to the earliest time at which the total post-treatment score improved to zero. Participants of 4 years age and younger underwent investigator assessment of HAE-related pain (cutaneous, abdominal, and laryngeal) using the FLACC comportmental pain scale. Each of the 5 categories was scored from 0 to 2. (F) Face: 0 (no particular expression/smile) - 2 (frequent to constant frown clenched jaw quivering chin); (L) Legs: 0 (normal position/relaxed) - 2 (kicking/legs drawn up); (A) Activity: 0 (lying quietly, normal position, moves easily) - 2 (arched rigid/jerking); (C) Cry: 0 (No cry [awake/asleep]) - 2 (crying steadily/screams/sobs or frequent complaints); (C) Consolability: 0 (content/relaxed) - 2 (difficult to console/comfort), resulting in a total score between 0 and 10.
Measured: From start of study drug administration up to 8.5 hours post-dose
Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration
Rescue medication was any medication used after the administration of icatibant which, in the opinion of the investigator, was immediately necessary to alleviate acute symptoms which are judged by the investigator as resultant from the current HAE attack. Time to first use of rescue medication prior to the onset of symptom relief was calculated from the time of study drug administration to the first use of rescue medication prior to the onset of symptom relief. This analysis was not performed since as per protocol, "This analysis will only be performed if there are at least 5 participants for a given attack who used rescue medication prior to attaining symptom relief".
Measured: From the start of study drug administration up to 52 hours post-dose
Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1
The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours postdose were reported.
Measured: From 2 hours post-dose to 4 hours post-dose
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
The investigator used a symptom score to assess the severities of symptoms of acute cutaneous, abdominal, and laryngeal attacks of HAE using the following 5- point scale: 0=none (absence of symptoms), 1=mild (no to mild interference with daily activities), 2=moderate (moderate interference with daily activities), 3=severe (severe interference with daily activities) and 4=very severe (very severe interference with daily activities). The number of participants with a worsened severity of HAE symptoms at 4 hours post-dose from 2 hours post-dose were reported.
Measured: From 2 hours post-dose to 4 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study start27 Jan 2012
- Primary completion12 Mar 2018
- Study completion12 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Angioedema (HAE)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386658
- Sponsor's protocol ID
- HGT-FIR-086
- Other IDs
- 2011-003825-81
- Status last verified
- May 2021
- First submitted
- 28 Jun 2011
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Publications
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.
PubMed 28601641
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01386658
- Acronym / sponsor ID
- HGT-FIR-086
- Conditions
- Hereditary Angioedema (HAE)
- Keywords
- Efficacy, Hereditary angioedema, HAE, Pediatric, Children, Pharmacokinetics, Safety, Firazyr
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 27 Jan 2012 (actual)
- Primary completion
- 12 Mar 2018 (actual)
- Study completion
- 12 Mar 2018 (actual)
- First posted
- 1 Jul 2011 (estimated)
- Results
- Posted 25 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Icatibant | Experimental | Drug: icatibantSingle dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Two through <18 years of age at the time of first HAE 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).
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| icatibantAlso: FirazyrSingle dose of icatibant 0.4 mg/kg subcutaneous(SC) up to a maximal dose of 30 mg | Drug | Icatibant |
Primary outcome
Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant
Time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1
Time to peak concentration (Tmax) of a single SC dose of icatibant was reported.
Maximum Plasma Concentration (Cmax) of a Single Subcutaneous (SC) Dose of Icatibant
Time frame: 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 SC dose of icatibant was reported.
Total Plasma Clearance (CL/F) of a Single Subcutaneous (SC) Dose of Icatibant
Time frame: 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 SC dose of icatibant was reported.
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
Time frame: 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 4 hours post-dose (AUC0-4) of a single SC dose of icatibant was reported.
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
Time frame: 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 6 hours post-dose (AUC0-t) of a single SC dose of icatibant was reported.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of a Single Subcutaneous (SC) Dose of Icatibant
Time frame: 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 SC dose of icatibant was reported.
Volume of Distribution (Vz/F) of a Single Subcutaneous (SC) Dose of Icatibant
Time frame: 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 SC dose of icatibant was reported.
Elimination Half-life (t1/2) of a Single Subcutaneous (SC) Dose of Icatibant
Time frame: 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 SC dose of icatibant was reported.
Number of Participants With Clinically Significant Changes in Vital Signs
Time frame: Pre-dose up to 97 days post-dose
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.
Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs)
Time frame: 6 - 8 hours post-dose on Day 1
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.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Evaluations
Time frame: Pre-dose up to 97 days post-dose
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.
Number of Participants Who Reported Presence of Anti-icatibant Antibodies
Time frame: Pre-dose up to 97 days post-dose
The number of participants who reported anti-icatibant antibodies were reported.
Number of Participants With Adverse Events (AEs)
Time frame: From the start of study drug administration up to 97 days post-dose
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.
Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 1
Time frame: 1 h post-dose on Day 1 up to 9 days post-dose
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.
Number of Participants Who Reported Injection Site Reactions (ISR) for Icatibant Exposure Number 2 and 3
Time frame: 1 h post-dose up to 9 days post-dose
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.
Number of Participants With Clinically Significant Changes in Reproductive Hormones
Time frame: Pre-dose up to 97 days post-dose
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.
13 secondary outcomes
Time to Onset of Symptom Relief (TOSR) for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From start of study drug administration up to 8.5 hours post-dose
Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 1
Time frame: From start of study drug administration up to 8.5 hours post-dose
Time to Minimum Symptoms for Composite Investigator-Assessed Symptom Scores for Icatibant Exposure Number 2 and 3
Time frame: From start of study drug administration up to 12 hours post-dose
Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 1
Time frame: From start of study drug administration up to 52 hours post-dose
Time to Minimum Symptom for Faces Pain Scale-Revised (FPS-R) Scores for Icatibant Exposure Number 2 and 3
Time frame: From start of study drug administration up to 28 hours post-dose
Time to Minimum Symptom for Faces, Legs, Activity, Cry, and Consolability (FLACC) Scores
Time frame: From start of study drug administration up to 8.5 hours post-dose
Time to Use of Rescue Medication for the Treatment of Symptoms of the Hereditary Angioedema (HAE) Attack Following Study Drug Administration
Time frame: From the start of study drug administration up to 52 hours post-dose
Number of Participants With Worsened Intensity of Clinical Hereditary Angioedema (HAE) Symptoms Between 2 and 4 Hours After Treatment With Icatibant Exposure Number 1
Time frame: From 2 hours post-dose to 4 hours post-dose
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
Time frame: From 2 hours post-dose to 4 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28601641Farkas 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.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
26 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing icatibant in people with Hereditary Angioedema (HAE), run by Shire at 26 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Germany, Israel, Spain, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Peak Concentration (Tmax) of a Single Subcutaneous (SC) Dose of Icatibant (time frame: Pre-dose; 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours post-dose on Day 1). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01386658, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.