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

Shire

Status and phase: Completed; Phase 3

Conditions: Hereditary Angioedema

Treatments: Drug: Tranexamic Acid; Drug: S.C. Placebo; Drug: Icatibant; Drug: Oral Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00500656

2004-001540-71 (EudraCT Number)

JE049 #2102

Details and patient eligibility

About

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

Full 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.

Enrollment: 85 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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85 participants in 4 patient groups

Randomized controlled -Icatibant

Experimental group

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

Treatment:

Drug: Oral Placebo

Drug: Icatibant

Randomized controlled-Tranexamic acid

Active Comparator group

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

Treatment:

Drug: Tranexamic Acid

Drug: S.C. Placebo

Controlled Open-label / laryngeal attack

Experimental group

Description:

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

Treatment:

Drug: Icatibant

Untreated patients at the baseline

Experimental group

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

Treatment:

Drug: Icatibant