A Study of Icatibant in Patients With Acute Attacks of He... | NCT00912093

NCT00912093

ID	Type	Description	Link
2009-015606-19	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Single subcutaneous injection of matching placebo	Drug: Placebo
Icatibant	Experimental	Single subcutaneous injection of icatibant, 30 mg	Drug: Icatibant

Name	Type	Description	Arm Group Labels	Other Names
Icatibant	Drug	Single subcutaneous injection of icatibant, 30 mg	Icatibant

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient	Time to onset of symptom relief was calculated from study drug administration to onset of symptom relief, where onset of symptom relief was defined as the earliest of 3 consecutive measurements in which there was a 50% reduction from pretreatment in composite VAS score. Composite VAS score comprised 3 symptoms, including skin swelling, skin pain, and abdominal pain, for cutaneous and abdominal attacks and 5 symptoms, including skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change, for laryngeal attacks. Subjects who did not achieve symptom relief within the observation period were censored at the last observation time.	Up to 120 hours post-dose

Secondary Outcomes

Measure	Description	Time Frame
Time to Onset of Primary Symptom Relief	Time to primary symptom relief was calculated from the time of study drug administration to the onset of primary symptom relief, where onset of primary symptom relief was determined using the subject-assessed VAS score for a single primary symptom (determined by edema location) and defined as the earliest of 3 consecutive non-missing measurements in which a pre-specified reduction from the pretreatment value was met. Subjects who did not achieve primary symptom relief within the observation period were censored at the last observation time.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Each patient must meet the following criteria to be enrolled in this study.

The patient is ≥18 years old at the time of informed consent.
The patient has a documented diagnosis of HAE type I or II. The diagnosis will be confirmed either by documented decreased C4 levels and/or immunogenic or functional C1-INH deficiency results (<50% of normal levels) consistent with HAE types I and II or by medical history.
The current HAE attack must be in the cutaneous, abdominal and/or laryngeal (inclusive of laryngeal and pharyngeal) areas.
Cutaneous or abdominal HAE attacks must be moderate to very severe as determined by investigator global assessment at pre-treatment assessments
The patient must report at least 1 VAS score ≥ 30mm
The patient commences treatment within 6 hours of the attack becoming at least mild (laryngeal) or moderate (non-laryngeal) in severity, but not more than 12 hours after the onset of the attack.
Women of childbearing potential must have a negative urine pregnancy test and must use appropriate methods to prevent pregnancy during their participation in the study.

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study.

The patient has a diagnosis of angioedema other than HAE type I or II.
The patient has received previous treatment with icatibant.
The patient has participated in a clinical trial and has received treatment with another investigational medicinal product within the past 30 days.
The patient has received treatment with any pain medication since the onset of the current angioedema attack.
The patient has received replacement therapy (fresh frozen plasma [FFP], C1-INH products) less than 5 days (120 hours) from the onset of the current angioedema attack.
The patient is receiving treatment with angiotensin converting enzyme (ACE) inhibitors.
Evidence of coronary artery disease based on medical history or screening examination in particular unstable angina pectoris or severe coronary heart disease;
The patient has a serious concomitant illness or condition that, in the opinion of the Investigator, would be a contraindication for participation in the trial.
The patient is pregnant or breastfeeding.

Contacts/Locations Module

Name	Affiliation	Role
Study Director	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Primary Care Associates of Alabaster		Alabaster	Alabama	35007	United States
UAB Lung Health Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
26556097	Derived	Lumry WR, Farkas H, Moldovan D, Toubi E, Baptista J, Craig T, Riedl M. Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3. Int Arch Allergy Immunol. 2015;168(1):44-55. doi: 10.1159/000441060. Epub 2015 Nov 11.
25198193	Derived	Maurer M, Longhurst HJ, Fabien V, Li HH, Lumry WR. Treatment of hereditary angioedema with icatibant: efficacy in clinical trials versus effectiveness in the real-world setting. Allergy Asthma Proc. 2014 Sep-Oct;35(5):377-81. doi: 10.2500/aap.2014.35.3780. Epub 2014 Aug 6.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Randomized-Icatibant (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant, 30 mg in the controlled phase
FG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
BG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase
BG002	Randomized-Icatibant (Blinded Treatment)--Laryngeal	Subjects with mild to moderate laryngeal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
BG003	Randomized-Placebo (Blinded Treatment)-Laryngeal	Subjects with mild to moderate laryngeal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase
BG004	Open-Label Icatibant-Severe Laryngeal	Subjects with severe (post-amendment) or mild to severe (pre-amendment) laryngeal attacks of HAE treated with subcutaneous injection of icatibant 30 mg in the controlled phase
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00036.1± 13.69 BG00136.6± 11.18 BG00240.3± 6.66 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00027 BG00129 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

American Indian or Alaska Native

Title	Measurements
	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00026 BG00132 BG002

Weight (kg)

Count of Participants

Participants

Title

Denominators

Categories

<= 50 kg

Title	Measurements
	BG0004 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient

Time to onset of symptom relief was calculated from study drug administration to onset of symptom relief, where onset of symptom relief was defined as the earliest of 3 consecutive measurements in which there was a 50% reduction from pretreatment in composite VAS score. Composite VAS score comprised 3 symptoms, including skin swelling, skin pain, and abdominal pain, for cutaneous and abdominal attacks and 5 symptoms, including skin swelling, skin pain, abdominal pain, difficulty swallowing, and voice change, for laryngeal attacks. Subjects who did not achieve symptom relief within the observation period were censored at the last observation time.

Non-laryngeal Intent-to-Treat (nl-ITT) population included all subjects with non-laryngeal attacks of HAE randomized to treatment. Subjects were analyzed according to the randomized treatment regardless of the treatment actually received. This was the primary analysis population for efficacy.

Posted

Median

95% Confidence Interval

Hours

Up to 120 hours post-dose

ID	Title	Description
OG000	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
OG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase

Units	Counts
Participants	OG00043 OG00145

Title

Denominators

Categories

Title	Measurements
	OG0002.0(1.5 to 3.0) OG00119.8(6.1 to 26.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Peto-Peto Wilcoxon		<0.001														Superiority or Other (legacy)

Secondary

Time to Onset of Primary Symptom Relief

Time to primary symptom relief was calculated from the time of study drug administration to the onset of primary symptom relief, where onset of primary symptom relief was determined using the subject-assessed VAS score for a single primary symptom (determined by edema location) and defined as the earliest of 3 consecutive non-missing measurements in which a pre-specified reduction from the pretreatment value was met. Subjects who did not achieve primary symptom relief within the observation period were censored at the last observation time.

Posted

Median

95% Confidence Interval

Hours

Up to 120 hours post-dose

ID	Title	Description
OG000	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
OG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase

Secondary

Time to Almost Complete Symptom Relief

Time to almost complete symptom relief was calculated from the time of study drug administration to almost complete symptom relief, where almost complete symptom relief was defined as the earliest of 3 consecutive non-missing measurements in which all VAS scores <10 mm. Subjects who did not achieve almost complete symptom relief within the observation period were censored at the last observation time.

Posted

Median

95% Confidence Interval

Hours

Up to 120 Hours post treatment

ID	Title	Description
OG000	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
OG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase

Secondary

Time to Subject-Assessed Initial Symptom Improvement

Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the subject as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time.

Posted

Median

95% Confidence Interval

Hours

Up to 120 hours post-dose

ID	Title	Description
OG000	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
OG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase

Secondary

Time to Investigator-Assessed Initial Symptom Improvement

Time to initial symptom improvement was calculated from the time of study drug administration to initial symptom improvement as determined by the investigator as the time they felt symptoms were starting to improve. Subjects who did not achieve initial symptom improvement within the observation period were censored at the last observation time.

Posted

Median

95% Confidence Interval

Hours

Up to 120 hours post-dose

ID	Title	Description
OG000	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of icatibant 30 mg in the controlled phase
OG001	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Subjects with moderate to severe cutaneous or abdominal attacks of HAE randomized to receive a single subcutaneous injection of matching placebo in the controlled phase

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Controlled Phase - Icatibant (Randomized)	Subjects who were randomized to treatment and received a single subcutaneous injection of icatibant 30 mg in the controlled phase	0	46	8	46
EG001	Controlled Phase -Placebo (Randomized)	Subjects who were randomized to treatment and received a single subcutaneous injection of matching placebo in the controlled phase	5	46	12	46
EG002	Controlled Phase - Icatibant (Open Label)	Subjects who were not randomized and received a single subcutaneous injection of icatibant 30 mg in the controlled phase	0	6	0	6
EG003	Open Label Extension - Icatibant (Open Label)	Subjects who treated with icatibant 30 mg in the open label extension phase	7	82	23	82

Serious Adverse Events

Term	Organ System	Statistical Information
Myocardial infarction	Cardiac disorders	EG0000 events0 affected46 at risk EG0011 events1 affected46 at risk EG0020 events0 affected6 at risk EG0030 events0 affected82 at risk
Hereditary angioedema	Congenital, familial and genetic disorders	EG0000 events0 affected46 at risk EG0012 events2 affected46 at risk EG0020 events0 affected6 at risk EG003
Gastroenteritis	Infections and infestations	EG0000 events0 affected46 at risk EG0011 events1 affected46 at risk EG0020 events0 affected6 at risk EG003
Tracheostomy	Surgical and medical procedures	EG0000 events0 affected46 at risk EG0011 events1 affected46 at risk EG0020 events0 affected6 at risk EG003
Arrhythmia	Cardiac disorders	EG0000 events0 affected46 at risk EG0010 events0 affected46 at risk EG0020 events0 affected6 at risk EG003
Non-Cardiac Chest Pain	General disorders	EG0000 events0 affected46 at risk EG0010 events0 affected46 at risk EG0020 events0 affected6 at risk EG003
Pneumonia	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected46 at risk EG0010 events0 affected46 at risk EG0020 events0 affected6 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	EG0000 events0 affected46 at risk EG0010 events0 affected46 at risk EG0020 events0 affected6 at risk EG003
Cholecystitis	Hepatobiliary disorders	EG0000 events0 affected46 at risk EG0010 events0 affected46 at risk EG0020 events0 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Statistical Information
Hereditary angioedema	Congenital, familial and genetic disorders	EG0005 events5 affected46 at risk EG0019 events9 affected46 at risk EG0020 events0 affected6 at risk EG00317 events11 affected82 at risk
Headache	Nervous system disorders	EG0004 events3 affected46 at risk EG0013 events3 affected46 at risk EG0020 events0 affected6 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	EG0000 events0 affected46 at risk EG0010 events0 affected46 at risk EG0020 events0 affected6 at risk EG003

ID	Term
D054179	Angioedemas, Hereditary

Ancestor Terms

ID	Term
D000799	Angioedema
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D000081208	Hereditary Complement Deficiency Diseases
D000081207	Primary Immunodeficiency Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D014581	Urticaria
D017445	Skin Diseases, Vascular
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases
D007153	Immunologic Deficiency Syndromes

ID	Term
C065679	icatibant

Units	Counts
Participants	OG00043 OG00145