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

NCT00500656 | Completed Phase 3 Results DMC

• 2 other identifiers: JE049 #21022004-001540-71
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (1)

• 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.

  2 days

Secondary Outcomes (1)

• Time to Almost Complete Symptom Relief

  48 hours

Study Arms (4)

Randomized controlled -Icatibant

EXPERIMENTAL

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; Drug: Oral Placebo

Randomized controlled-Tranexamic acid

ACTIVE COMPARATOR

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; Drug: S.C. Placebo

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.

Drug: Icatibant

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 were treated in the open label phase with icatibant

Drug: Icatibant

Interventions

Icatibant DRUG

Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist.

Also known as: Brand name, Firazyr®

Controlled Open-label / laryngeal attack; Randomized controlled -Icatibant; Untreated patients at the baseline

Tranexamic Acid DRUG

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.

Randomized controlled-Tranexamic acid

Oral Placebo DRUG

hard capsule matched to tranexamic acid

Also known as: Placebo

Randomized controlled -Icatibant

S.C. Placebo DRUG

solution for injection, matched to icatibant for injection

Also known as: Placebo

Randomized controlled-Tranexamic acid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

Università degli Studi di Milano, Dipartimento di Medicina Interna

Milan, 20123, Italy

Location

Related Publications (3)

• 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.

  PMID: 17073887 RESULT

• 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.

  PMID: 24111645 DERIVED

• 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.

  PMID: 20818888 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

icatibant; Tranexamic Acid

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2007
• First Posted: July 13, 2007
• Study Start: March 1, 2005
• Primary Completion: July 25, 2006
• Study Completion: July 25, 2006
• Last Updated: June 9, 2021
• Results First Posted: June 9, 2014

Record last verified: 2021-05

Locations

IT (1)