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Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE) (FAST2)

Primary Purpose

Hereditary Angioedema

Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Icatibant
Tranexamic Acid
Oral Placebo
S.C. Placebo
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age above 18 years;
  • Documented diagnosis of HAE Type I or II (confirmed C1-INH deficiency);
  • Current edema in the cutaneous, abdominal and/or laryngeal areas;
  • Current edema moderate to severe according to the investigator's Symptom Score.

Exclusion Criteria:

  • Diagnosis of angioedema other than HAE,
  • Participation in a clinical trial of another investigational medicinal product (IMP)within the past month
  • Treatment with any pain medication since onset of the current angioedema attack
  • Treatment with replacement therapy, including C1-INH products, less than 3 days before onset of the current angioedema attack
  • Treatment with Tranexamic acid replacement therapy within a week before onset of the current angioedema attack
  • Treatment with ACE inhibitors
  • Contraindications for Tranexamic acid
  • Evidence of coronary artery disease based on medical history or Screening examination in particular unstable angina pectoris or severe coronary heart disease
  • Congestive heart failure (class 3 and 4)
  • Serum creatinine level of ≥ 250 μmol/L
  • Serious concomitant illness that the investigator considered to be a contraindication for participation in the trial
  • Pregnancy (as assessed prior to treatment) and/or breast-feeding

Sites / Locations

  • Università degli Studi di Milano, Dipartimento di Medicina Interna

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Arm Label

Randomized controlled -Icatibant

Randomized controlled-Tranexamic acid

Controlled Open-label / laryngeal attack

Untreated patients at the baseline

Arm Description

Subjects received S.C icatibant+ oral placebo Icatibant Form: solution for injection, 3 mL, 10 mg/mL Single dose: 30 mg (3 mL) Placebo Form: hard capsule Single dose: 2 capsules Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart

Subjects received oral Tranexamic acid+ S.C. placebo Tranexamic acid Form: over encapsulated film tablet Single dose: 1000 mg (2 capsules) Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart Placebo Form: solution for injection, matched to icatibant for injection Single dose: 3 mL Frequency: one subcutaneous injection in the abdominal region

Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.

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 were treated in the open label phase with icatibant

Outcomes

Primary Outcome Measures

Time to Onset of Symptom Relief.
The primary efficacy endpoint was Time to onset of symptom relief (TOSR) following treatment with either icatibant or tranexamic acid. The median time to onset of symptom relief for the icatibant group was compared to the the median time to onset of symptom relief for the tranexamic acid group. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the three 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.

Secondary Outcome Measures

Time to Almost Complete Symptom Relief
Almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least three consecutive measurements for all symptoms.

Full Information

First Posted
July 12, 2007
Last Updated
May 24, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00500656
Brief Title
Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)
Acronym
FAST2
Official Title
Randomised Double Blind, Controlled, Parallel Group, Multicentre Study of a Subcutaneous Formulation of Icatibant Versus Oral Tranexamic Acid for the Treatment of Hereditary Angioedema (HAE)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
March 1, 2005 (Actual)
Primary Completion Date
July 25, 2006 (Actual)
Study Completion Date
July 25, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary Outcome Measures: The primary endpoint was the time to onset of symptom relief of the first attack in the double blind phase. H0: λ icatibant/λ tranexamic acid =1 versus H1: λ icatibant/λ tranexamic acid ≠1 Where: λ icatibant refers to the hazard rate under icatibant and λ tranexamic acid refers to the hazard rate under tranexamic acid. Secondary Outcome Measures: Additional efficacy assessments (Time to Almost Complete Symptom Relief) Safety and tolerability Pharmacoeconomics
Detailed Description
This was a Phase III, randomised, double blind, double dummy, multicentre, controlled,parallel group study of a 30 mg s.c. formulation of icatibant for the treatment of patients with moderate to very severe symptoms of cutaneous and/or abdominal symptoms of HAE. The study consisted of two parts: controlled phase and OLE phase. For the primary endpoint, Efficacy was determined by evaluating the differences in study outcomes using a Visual Analogue Scale for patients treated with icatibant and tranexamic acid.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
85 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Randomized controlled -Icatibant
Arm Type
Experimental
Arm Description
Subjects received S.C icatibant+ oral placebo Icatibant Form: solution for injection, 3 mL, 10 mg/mL Single dose: 30 mg (3 mL) Placebo Form: hard capsule Single dose: 2 capsules Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart
Arm Title
Randomized controlled-Tranexamic acid
Arm Type
Active Comparator
Arm Description
Subjects received oral Tranexamic acid+ S.C. placebo Tranexamic acid Form: over encapsulated film tablet Single dose: 1000 mg (2 capsules) Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart Placebo Form: solution for injection, matched to icatibant for injection Single dose: 3 mL Frequency: one subcutaneous injection in the abdominal region
Arm Title
Controlled Open-label / laryngeal attack
Arm Type
Experimental
Arm Description
Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.
Arm Title
Untreated patients at the baseline
Arm Type
Experimental
Arm Description
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 were treated in the open label phase with icatibant
Intervention Type
Drug
Intervention Name(s)
Icatibant
Other Intervention Name(s)
Brand name, Firazyr®
Intervention Description
Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid
Intervention Description
over encapsulated film tablet an anti-fibrinolytic agent,is used in some European countries for the treatment of acute oedema episodes and the continuous prophylaxis of HAE.
Intervention Type
Drug
Intervention Name(s)
Oral Placebo
Other Intervention Name(s)
Placebo
Intervention Description
hard capsule matched to tranexamic acid
Intervention Type
Drug
Intervention Name(s)
S.C. Placebo
Other Intervention Name(s)
Placebo
Intervention Description
solution for injection, matched to icatibant for injection
Primary Outcome Measure Information:
Title
Time to Onset of Symptom Relief.
Description
The primary efficacy endpoint was Time to onset of symptom relief (TOSR) following treatment with either icatibant or tranexamic acid. The median time to onset of symptom relief for the icatibant group was compared to the the median time to onset of symptom relief for the tranexamic acid group. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the three 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 Frame
2 days
Secondary Outcome Measure Information:
Title
Time to Almost Complete Symptom Relief
Description
Almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least three consecutive measurements for all symptoms.
Time Frame
48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age above 18 years; Documented diagnosis of HAE Type I or II (confirmed C1-INH deficiency); Current edema in the cutaneous, abdominal and/or laryngeal areas; Current edema moderate to severe according to the investigator's Symptom Score. Exclusion Criteria: Diagnosis of angioedema other than HAE, Participation in a clinical trial of another investigational medicinal product (IMP)within the past month Treatment with any pain medication since onset of the current angioedema attack Treatment with replacement therapy, including C1-INH products, less than 3 days before onset of the current angioedema attack Treatment with Tranexamic acid replacement therapy within a week before onset of the current angioedema attack Treatment with ACE inhibitors Contraindications for Tranexamic acid Evidence of coronary artery disease based on medical history or Screening examination in particular unstable angina pectoris or severe coronary heart disease Congestive heart failure (class 3 and 4) Serum creatinine level of ≥ 250 μmol/L Serious concomitant illness that the investigator considered to be a contraindication for participation in the trial Pregnancy (as assessed prior to treatment) and/or breast-feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Università degli Studi di Milano, Dipartimento di Medicina Interna
City
Milano
ZIP/Postal Code
20123
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
17073887
Citation
Bas M, Bier H, Greve J, Kojda G, Hoffmann TK. Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant. Allergy. 2006 Dec;61(12):1490-2. doi: 10.1111/j.1398-9995.2006.01197.x. No abstract available.
Results Reference
result
PubMed Identifier
24111645
Citation
Bas M, Greve J, Hoffmann TK, Reshef A, Aberer W, Maurer M, Kivity S, Farkas H, Floccard B, Arcoleo F, Martin L, Sitkauskiene B, Bouillet L, Schmid-Grendelmeier P, Li H, Zanichelli A. Repeat treatment with icatibant for multiple hereditary angioedema attacks: FAST-2 open-label study. Allergy. 2013 Nov;68(11):1452-9. doi: 10.1111/all.12244. Epub 2013 Sep 21.
Results Reference
derived
PubMed Identifier
20818888
Citation
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. Erratum In: N Engl J Med. 2010 Oct 7;363(15):1486.
Results Reference
derived

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Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (HAE)

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