A Study of Icatibant in Patients With Acute Attacks of Hereditary Angioedema (FAST-3)

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Hereditary Angioedema
Interventions:	Drug: Icatibant; Drug: Placebo

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
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
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
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
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
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

Participant Flow for 2 periods

Period 1:   The Controlled Phase

	Randomized-Icatibant (Blinded Treatment)-Non-laryngeal	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Randomized-Icatibant (Blinded Treatment)-Laryngeal	Randomized-Placebo (Blinded Treatment)-Laryngeal	Open-Label Icatibant-Severe Laryngeal
STARTED	43	45	3	2	5
COMPLETED	43	43	3	2	4
NOT COMPLETED	0	2	0	0	1
Death	0	1	0	0	0
Medical Condition	0	1	0	0	0
Lost to Follow-up	0	0	0	0	1

Period 2:   The Open Label Extension (OLE) Phase

	Randomized-Icatibant (Blinded Treatment)-Non-laryngeal	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Randomized-Icatibant (Blinded Treatment)-Laryngeal	Randomized-Placebo (Blinded Treatment)-Laryngeal	Open-Label Icatibant-Severe Laryngeal
STARTED	38	35	3	2	4
COMPLETED	38	35	3	2	4
NOT COMPLETED	0	0	0	0	0

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
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
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
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
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
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
Total	Total of all reporting groups

Baseline Measures

	Randomized-Icatibant (Blinded Treatment)--Non-laryngeal	Randomized-Placebo (Blinded Treatment)-Non-laryngeal	Randomized-Icatibant (Blinded Treatment)--Laryngeal	Randomized-Placebo (Blinded Treatment)-Laryngeal	Open-Label Icatibant-Severe Laryngeal	Total
Overall Participants Analyzed; [Units: Participants]	43	45	3	2	5	98
Age; [Units: Years]; Mean (Standard Deviation)	36.1 (13.69)	36.6 (11.18)	40.3 (6.66)	50.0 (22.63)	41.6 (11.78)	37.0 (12.46)
Gender; [Units: Participants]
Female	27	29	2	1	2	61
Male	16	16	1	1	3	37
Race/Ethnicity, Customized; [Units: Participants]
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	0	0	0	0
Black or African American	3	0	0	0	0	3
Native Hawaiian or Other Pacific	0	0	0	0	0	0
White	38	40	3	2	4	87
Other	2	5	0	0	1	8
Region of Enrollment; [Units: Participants]
United States	26	32	2	2	3	65
Hungary	3	1	0	0	0	4
Canada	1	0	0	0	0	1
Ukraine	0	1	0	0	0	1
Romania	3	1	1	0	0	5
Australia	2	3	0	0	0	5
Russian Federation	2	1	0	0	0	3
South Africa	2	1	0	0	1	4
Israel	4	5	0	0	1	10
Weight (kg); [Units: Participants]
<= 50 kg	4	2	0	0	0	6
>50-75 kg	16	20	1	2	0	39
>75-100 kg	14	13	1	0	3	31
>100 kg	9	10	1	0	2	22

  Outcome Measures

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1. Primary:

Time to Onset of Symptom Relief for an Acute Attack, as Assessed by the Patient [ Time Frame: Up to 120 hours post-dose ]

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2. Secondary:

Time to Onset of Primary Symptom Relief [ Time Frame: Up to 120 hours post-dose ]

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3. Secondary:

Time to Almost Complete Symptom Relief [ Time Frame: Up to 120 Hours post treatment ]

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4. Secondary:

Time to Subject-Assessed Initial Symptom Improvement [ Time Frame: Up to 120 hours post-dose ]

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5. Secondary:

Time to Investigator-Assessed Initial Symptom Improvement [ Time Frame: Up to 120 hours post-dose ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

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Certain Agreements:  

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: Shire’s agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial’s multi-center publication.

Results Point of Contact:  

Name/Title: Alan Kimura, MD, PhD
Organization: Shire
phone: 1-617-482-0738
e-mail: akimura@shire.com

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

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.

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.

Baş M. Clinical efficacy of icatibant in the treatment of acute hereditary angioedema during the FAST-3 trial. Expert Rev Clin Immunol. 2012 Nov;8(8):707-17. doi: 10.1586/eci.12.67.

Lumry WR, Li HH, Levy RJ, Potter PC, Farkas H, Moldovan D, Riedl M, Li H, Craig T, Bloom BJ, Reshef A. Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011 Dec;107(6):529-37. doi: 10.1016/j.anai.2011.08.015. Epub 2011 Oct 5.

Responsible Party:	Shire
ClinicalTrials.gov Identifier:	NCT00912093 History of Changes
Other Study ID Numbers:	HGT-FIR-054; 2009-015606-19 ( EudraCT Number )
First Submitted:	June 2, 2009
First Posted:	June 3, 2009
Results First Submitted:	July 11, 2014
Results First Posted:	August 6, 2014
Last Update Posted:	September 22, 2014