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| ID | Type | Description | Link |
|---|---|---|---|
| FAST1 | Other Identifier | Shire HGT |
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The purpose of this study is to assess the efficacy and safety of Icatibant, a bradykinin antagonist in the treatment of acute cutaneous and/or abdominal attacks in patients with hereditary angioedema (HAE).
This Phase II/III study consisted of two parts: A controlled phase and An Open label extension(OLE) phase. The controlled phase describes the double blind part of the study and was intended to evaluate the efficacy of icatibant in decreasing the time to onset of symptom relief compared with placebo for the first treated cutaneous and/or abdominal attack in randomised patients. Patients experienced a laryngeal attack were not randomised, but treated with open label icatibant according to the controlled phase procedures and assessments. The outcome of this group was to be reported descriptively. After treatment of the first attack in the controlled phase, the patients were eligible to enter the OLE phase. In the OLE phase, patients who experienced angioedema attacks severe enough to warrant treatment were to be treated with s.c. icatibant as appropriate until the end of the study.The OLE phase became a modified open label extension where all 56 patients who had been randomised and the last randomised patient had concluded the double-blind phase. The modified open label extension period permitted treatment for patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the double blind phase was still ongoing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Icatibant- Randomized | Experimental | Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack. |
|
| Placebo-Randomized | Placebo Comparator | Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack. |
|
| Controlled Open-label / laryngeal attack | Experimental | Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. |
|
| Untreated Patients at the baseline | Experimental | Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing (they were not treated during the Controlled phase but treated with icatibant during the Open Label Extension Phase (OLE) ) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Icatibant | Drug | 30 mg (3mL) subcutaneous icatibant injection in the abdominal region |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Onset of Symptom Relief (TOSR) | The primary efficacy endpoint was TOSR assessed by the patient using a Visual Analogue Scale (VAS). The VAS is a scale used to measure intensity of each symptom of the attack at baseline and at the pre-determined time points throughout treatment period. It consists of a horizontal 10cm line, with the 0 point corresponding to a state where patient experiences no symptoms at all and the 10cm point represents the worst symptoms ever experienced by patient. The patient indicates his/her current state of symptoms by drawing a mark across the horizontal line. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the 3 primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain. The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe. | 5 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Regression (Start of Improvement) According to Patient | This parameter assessed the time to regression (start of improvement) of observable(visible) symptoms according to the patients. Patients were asked "Report date and time when you feel that your symptoms start to improve". | 5 days |
| Time to Almost Complete Symptom Relief |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgetown University Hospital, Lombardi Cancer Center | Washington D.C. | District of Columbia | 20007-2197 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24749847 | Derived | Malbran A, Riedl M, Ritchie B, Smith WB, Yang W, Banerji A, Hebert J, Gleich GJ, Hurewitz D, Jacobson KW, Bernstein JA, Khan DA, Kirkpatrick CH, Resnick D, Li H, Fernandez Romero DS, Lumry W. Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial. Clin Exp Immunol. 2014 Aug;177(2):544-53. doi: 10.1111/cei.12358. | |
| 20818888 |
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Patients must have an eligible HAE attack to be randomized.64 patients were in the controlled phase(27icatibant,29 placebo,8subjects with laryngeal attacks were treated with open label icatibant).A total of 72 were treated in the open label phase(20 entered directly into the OLE phase+ 52 from the controlled phase).
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| ID | Title | Description |
|---|---|---|
| FG000 | Randomized -Icatibant | Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack. |
| FG001 | Randomized -Placebo | Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack. |
| FG002 | Controlled Open-label / Laryngeal Attack | Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. |
| FG003 | Untreated Patients at the Baseline | Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| The Controlled Phase |
| |||||||||||||
| The Open Label Extension (OLE) Phase |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Randomized -Icatibant | Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack. |
| BG001 | Randomized -Placebo | Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Onset of Symptom Relief (TOSR) | The primary efficacy endpoint was TOSR assessed by the patient using a Visual Analogue Scale (VAS). The VAS is a scale used to measure intensity of each symptom of the attack at baseline and at the pre-determined time points throughout treatment period. It consists of a horizontal 10cm line, with the 0 point corresponding to a state where patient experiences no symptoms at all and the 10cm point represents the worst symptoms ever experienced by patient. The patient indicates his/her current state of symptoms by drawing a mark across the horizontal line. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the 3 primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain. The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe. | Time to onset of symptom relief - Controlled phase - ITT population (patients experiencing moderate to very severe acute cutaneous and/or abdominal HAE attacks) | Posted | Median | Inter-Quartile Range | Hours | 5 days |
An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Controlled Phase- Icatibant (Randomized Subjects ) | Patients who were randomized to icatibant in the controlled and experienced adverse events while participating in the controlled phase. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| HAE attack | Congenital, familial and genetic disorders | Hereditary Angioedem | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Investigations | MedDRA 8.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D000799 | Angioedema |
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
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| ID | Term |
|---|---|
| C065679 | icatibant |
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|
| Placebo | Drug | Solution for injection, matched to study drug Single dose: 3 mL |
|
The time to almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least 3 consecutive measurements for all symptom. |
| 5 days |
| Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, Bork K, Lumry W, Aberer W, Bier H, Bas M, Greve J, Hoffmann TK, Farkas H, Reshef A, Ritchie B, Yang W, Grabbe J, Kivity S, Kreuz W, Levy RJ, Luger T, Obtulowicz K, Schmid-Grendelmeier P, Bull C, Sitkauskiene B, Smith WB, Toubi E, Werner S, Anne S, Bjorkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hebert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernandez Romero DS, Zanichelli A, Arcoleo F, Knolle J, Kravec I, Dong L, Zimmermann J, Rosen K, Fan WT. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-41. doi: 10.1056/NEJMoa0906393. |
| COMPLETED |
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| NOT COMPLETED |
|
| BG002 | Controlled Open-label / Laryngeal Attack | patients who received first treatment Open-Label due to laryngeal symptoms |
| BG003 | Untreated Patients at the Baseline | Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|
| OG000 | Randomized -Icatibant | 27 Patients were randomized to icatibant in the controlled phase after they had an eligible first in-study attack. |
| OG001 | Randomized -Placebo | 29 Patients were randomized to placebo in the controlled phase after they had an eligible first in-study attack. |
|
|
|
| Secondary | Time to Regression (Start of Improvement) According to Patient | This parameter assessed the time to regression (start of improvement) of observable(visible) symptoms according to the patients. Patients were asked "Report date and time when you feel that your symptoms start to improve". | Posted | Median | Inter-Quartile Range | Hours | 5 days |
|
|
|
|
| Secondary | Time to Almost Complete Symptom Relief | The time to almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least 3 consecutive measurements for all symptom. | Posted | Median | Inter-Quartile Range | Hours | 5 days |
|
|
|
|
| 0 |
| 27 |
| 12 |
| 27 |
| EG001 | Controlled Phase- Placebo (Randomized Subjects | Patients who were randomized to placebo in the controlled phase and experienced adverse events while participating in the controlled phase. | 0 | 29 | 19 | 29 |
| EG002 | Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) | This represents adverse events during the controlled phase that were experienced by Patients with laryngeal symptoms at the baseline and were treated with open label icatibant during the controlled phase. | 1 | 8 | 6 | 8 |
| EG003 | Open Label Extension Phase- Icatibant (Previously Randomized) | Patients who were randomized to either icatibant or placebo in the controlled phase and experienced adverse events while participating in the open label extension phase. | 3 | 49 | 39 | 49 |
| EG004 | Open Label Extension -Icatibant (Subjects w/ Laryngeal Attack) | This represents adverse events during the open label extension phase that were experienced by Patients with laryngeal symptoms at the baseline and got treated with open label icatibant during the controlled phase. | 0 | 3 | 3 | 3 |
| EG005 | Open Label Extension Phase(Untreated Patients at the Baseline) | This represents adverse events experienced by Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing. | 0 | 20 | 17 | 20 |
| Pancreatitis | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
|
| Chest Pain | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Headache/Migraine | Nervous system disorders | MedDRA 8.1 | Systematic Assessment |
|
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA 8.1 | Systematic Assessment | HAE attacks were over-reported as AEs as some investigators reported new attacks as AEs in addition to worsening of attacks in Icatibant treated patients. |
|
| Nausea | Gastrointestinal disorders | MedDRA 8.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 8.1 | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 8.1 | Systematic Assessment |
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| Infections | Infections and infestations | MedDRA 8.1 | Systematic Assessment |
|
| Administration site conditions | General disorders | MedDRA 8.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 8.1 | Systematic Assessment |
|
| Blood Creatine Phosphokinase Increased | Investigations | MedDRA 8.1 | Systematic Assessment |
|
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| D012871 |
| Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007153 | Immunologic Deficiency Syndromes |