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

• ClinicalTrials.gov Identifier: NCT00500656
• Recruitment Status: Completed
• First Posted: July 13, 2007
• Results First Posted: June 9, 2014
• Last Update Posted: February 16, 2015
• Sponsor: Shire
• Information provided by (Responsible Party): Shire

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

Condition or disease	Intervention/treatment	Phase
Hereditary Angioedema	Drug: Icatibant; Drug: Tranexamic Acid; Drug: Oral Placebo; Drug: S.C. Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: March 2005
• Actual Primary Completion Date: March 2008
• Actual Study Completion Date: March 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Randomized controlled -Icatibant; 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	Drug: Icatibant; Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.; Other Name: Brand name, Firazyr®; Drug: Oral Placebo; hard capsule matched to tranexamic acid; Other Name: Placebo
Active Comparator: Randomized controlled-Tranexamic acid; 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	Drug: Tranexamic Acid; 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.; Drug: S.C. Placebo; solution for injection, matched to icatibant for injection; Other Name: Placebo
Experimental: 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.	Drug: Icatibant; Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.; Other Name: Brand name, Firazyr®
Experimental: 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 were treated in the open label phase with icatibant	Drug: Icatibant; Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.; Other Name: Brand name, Firazyr®

Outcome Measures

Primary Outcome Measures :

1. Time to Onset of Symptom Relief. [ Time Frame: 2 days ]

   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 :

1. Time to Almost Complete Symptom Relief [ Time Frame: 48 hours ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

Università degli Studi di Milano, Dipartimento di Medicina Interna

Milano, Italy, 20123

Sponsors and Collaborators

Shire

Investigators

• Principal Investigator: Marco Cicardi, Prof. Dr.; University of Milan

More Information

Additional Information:

Related Info 

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Baş 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.

Cicardi M, Banerji A, Bracho F, Malbrán 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, Anné S, Björkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hébert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernández 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.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00500656
• Other Study ID Numbers: JE049 #2102; 2004-001540-71 ( EudraCT Number )
• First Posted: July 13, 2007
• Results First Posted: June 9, 2014
• Last Update Posted: February 16, 2015
• Last Verified: May 2014

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Genetic Diseases, Inborn; Icatibant; Tranexamic Acid; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Bradykinin B2 Receptor Antagonists; Bradykinin Receptor Antagonists; Complement Inactivating Agents; Immunosuppressive Agents