Clinical trial NCT00097695: Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema
Official title: Randomized, Double Blind, Placebo-Controlled, Multicenter Study of a Subcutaneous Formulation of Icatibant for the Treatment of Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Angioedema
Keywords: Hereditary Angioedema
C1 inhibitor deficiency
HAE
Icatibant
Bradykinin antagonist
acute attack
subcutaneous
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2004-11-29
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age above 18 years;
* Documented diagnosis of HAE Type I or II (confirmed complement 1 esterase inhibitor \[C1-INH\] deficiency);
* Current edema be in the cutaneous, abdominal and/or laryngeal areas;
* Current edema be moderate to severe according to the investigator's Symptom Score.

Exclusion Criteria:

* Diagnosis of angioedema other than HAE, for example, acquired angioedema (AAE);
* 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 edema attack;
* Treatment with replacement therapy, including C1-INH products (e.g. human C1-INH preparations), less than 3 days from onset of the current edema attack;
* Treatment with ACE inhibitors (e.g. Lotensin, Prinivil, Accupril);
* Evidence of severe, symptomatic coronary artery disease based on medical history or screening examination;
* Serious concomitant illnesses that the physician considers to be a contraindication for participation in the trial;
* Pregnancy and/or breast-feeding.

Primary outcomes:
measure: Time to Onset of Symptom Relief (TOSR)
timeFrame: 5 days
Secondary outcomes:
measure: Time to Regression (Start of Improvement) According to Patient
timeFrame: 5 days
measure: Time to Almost Complete Symptom Relief
timeFrame: 5 days
Other outcomes:
Locations:
city: Washington
country: United States
facility: Georgetown University Hospital, Lombardi Cancer Center
state: District of Columbia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
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.