Clinical Trials Register

Summary
EudraCT Number:	2011-003825-81
Sponsor's Protocol Code Number:	HGT-FIR-086
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-11-14
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-003825-81

A.3

Full title of the trial

A Multicenter, Open-Label, Non-Randomized Study to Assess the Pharmacokinetics, Tolerability, and Safety of a Single Subcutaneous Administration of Icatibant in Children and Adolescents with Hereditary Angioedema

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical study intended to measure in the bodies of children and adolescents how drug Icatibant is absorbed and removed after a single administration (dose). The children and adolescents in the study will all have the disease called Hereditary Angioedema (which causes abnormal swelling of the body), this is because the drug icatibant is intended to treat Hereditary Angiodema. The study will also look for side effects that may be due to the drug

A.4.1

Sponsor's protocol code number

HGT-FIR-086

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01386658

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/238/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Shire Orphan Therapies, Inc
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Shire Orphan Therapies, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Shire Orphan Therapies, Inc
B.5.2	Functional name of contact point	Lawrence Charnas
B.5.3	Address:
B.5.3.1	Street Address	300 Shire Way
B.5.3.2	Town/ city	Lexington
B.5.3.3	Post code	MA 02421
B.5.3.4	Country	United States
B.5.4	Telephone number	1617349 0200
B.5.5	Fax number	1781482 2956
B.5.6	E-mail	bbloom@shire.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Firazyr (icatibant) 30 mg solution for injection in pre filled syringe
D.2.1.1.2	Name of the Marketing Authorisation holder	Shire Orphan Therapies GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/03/133
D.3 Description of the IMP
D.3.1	Product name	Firazyr (icatibant) 30 mg solution for injection in pre filled syringe
D.3.2	Product code	JE049
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	icatibant
D.3.9.1	CAS number	138614-30-9
D.3.9.2	Current sponsor code	JE049
D.3.9.3	Other descriptive name	ICATIBANT ACETATE
D.3.9.4	EV Substance Code	SUB29718
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hereditary Angioedema

E.1.1.1

Medical condition in easily understood language

Hereditary angioedema (HAE) is a rare genetic condition, where the body has local swellings in various body parts including the hands, feet, face and airway, (throat).

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10019860
E.1.2	Term	Hereditary angioedema
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the PK, tolerability, and safety of a single SC dose of icatibant in children and adolescents with HAE during an acute HAE attack.

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of a single SC dose of icatibant in children and adolescents with HAE.
To evaluate levels of reproductive hormones after a single SC dose of icatibant in children
and adolescents with HAE.
To evaluate continued safety of icatibant in pubertal/postpubeertal children after repeat exposure.
To evaluate reproductive hormone levels in pubertal/postpubeertal children after repeat exposure.
To evaluate the efficacy of icatibant in pubertal/postpubeertal children after repeat exposure.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Two through 17 years of age, inclusive (ie, from the second birthday until the day prior to the eighteenth birthday) at the time of the subject’s first HAE attack treated with icatibant as part of this study.
2. Documented diagnosis of HAE Type I or II. Diagnosis must be C1-1NH deficiency (C1-1NH protein level below the lower limit of normal and/or functional level <50% of normal). Diagnosis may be on the basis of historic data or by diagnostic testing conducted at the time of screening. Inclusion will be permitted initially based on medical history only if a clear diagnosis has been made based on all of the following criteria
-Family history
-Characteristic attack manifestations/recurrent attacks
-Historical N1-1NH deficiency as demonstrated by immunologic or functional test results
-Exclusion of other forms of angioedema
-Subsequent confirmation of the diagnosis to be made on the basis of C1-1NH level of function (all subjects)
3. Informed consent (and subject assent as appropriate) signed by the subject’s parent(s) or legal guardian(s).

E.4

Principal exclusion criteria

1. Diagnosis of angioedema other than HAE.
2. Participation in another clinical trial that involves use of any investigational product (drug of device) within 30 days prior to study enrollment or at any time during the study.
3. Any known factor/disease that might interfere with the treatment compliance, study conduct or result interpretation.
4. Congenital or acquired cardiac anomalies that interfere significantly with cardiac function.
5. Treatment with ACE inhibitors within 7 days prior to treatment.
6. Use of hormonal contraception within the 90 days prior to treatment.
7. Androgen use (eg, stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) within the 90 days prior to treatment.
8. The subject is pregnant or breastfeeding.
9. A physical condition that interferes with pubertal status determination

E.5 End points

E.5.1

Primary end point(s)

The PK profile of icatibant after a single SC injection in pediatric subjects treated for acute attacks of HAE.
The tolerability and safety of SC icatibant as assessed by injection site reactions, AEs, vital signs, ECG recordings, physical examination, clinical laboratory parameters (serum chemistry [including liver function tests], hematology, urinalysis), reproductive hormone levels, and immunogenicity (presence of anti-icatibant antibodies).

E.5.1.1

Timepoint(s) of evaluation of this end point

Post-Treatment Day 1 through Day 8 (±1 days)
Follow-up Day 9 through Day 90 (±7 days)
Two additional icatibant-treated attacks for a total of 3 icatibant-treated attacks
(Pubertal/postpubertal subjects only)
Treatment Day 1
Post-Treatment Day 1 through Day 8 (±1 days)
Follow-up Day 9 through Day 90 (±7 days)

E.5.2

Secondary end point(s)

For all subjects (2 to 17 years of age): investigator assessment and scoring of cutaneous, abdominal, and laryngeal symptoms of acute HAE attacks by an investigator-rated symptom score.
- The time to onset of relief of symptoms, defined as the earliest time at which a 20% improvement is seen in the average post-treatment score with no worsening of any single component score.
- The time to minimal symptoms, defined as the earliest time post-treatment when all symptoms are either mild or absent based on the investigator-rated symptom score.
• For subjects ≥4 years of age only: subject self-assessment of HAE-related pain using the Faces Pain Scale-Revised (FPS-R). The time to onset of relief of symptoms, defined as the earliest time at which a 20% improvement is seen in the post-treatment score.
• For subjects <4 years of age only: investigator assessment of HAE-related pain using the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale. The time to onset of relief of symptoms, defined as the earliest time at which a 20% improvement is seen in the total post-treatment score.
• The incidence of rescue medication use.
• The proportion of subjects with worsened intensity of clinical HAE symptoms between 2 and 4 hours after treatment with SC icatibant using investigator-rated symptom scores.

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Germany

Hungary

Israel

Italy

Spain

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Once the sixteenth prepubertal subject and the twentieth pubertal/postpubertal subject has completed the 6 month follow-up after treatment for an initial attack, and the fifteenth pubertal/postpubertal subject has completed the 6 month follow-up after the third and final treatment, the study will be closed.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2011-11-14.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Paediatric subjects aged from 2 to 17 years

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The normal treatment will be used

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-01-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-05

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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