Clinical Trials Register

Summary
EudraCT Number:	2010-022784-35
Sponsor's Protocol Code Number:	Q4883g
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-03-03
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2010-022784-35

A.3

Full title of the trial

A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED SAFETY STUDY OF XOLAIR (OMALIZUMAB) IN PATIENTS WITH CHRONIC IDIOPATHIC URTICARIA (CIU) WHO REMAIN SYMPTOMATIC DESPITE TREATMENT WITH H1 ANTIHISTAMINES, H2 BLOCKERS, AND/OR LEUKOTRIENE RECEPTOR ANTAGONISTS

A.3.2

Name or abbreviated title of the trial where available

GLACIAL

A.4.1

Sponsor's protocol code number

Q4883g

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01264939

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/133/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Genentech, 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	Genentech Inc
B.4.2	Country	United States
B.4.1	Name of organisation providing support	Novartis
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Genentech Inc
B.5.2	Functional name of contact point	Kristi Miller/Global Regulatory
B.5.3	Address:
B.5.3.1	Street Address	1 DNA Way
B.5.3.2	Town/ city	South San Francisco
B.5.3.3	Post code	CA 94080-4990
B.5.4	Telephone number	001650225 1000
B.5.5	Fax number	001650467 3198

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	XOLAIR
D.2.1.1.2	Name of the Marketing Authorisation holder	Genentech Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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	OMALIZUMAB
D.3.9.1	CAS number	242138-07-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Information not present in EudraCT
D.3.11.11	Herbal medicinal product	Information not present in EudraCT
D.3.11.12	Homeopathic medicinal product	Information not present in EudraCT
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Powder for solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

CHRONIC IDIOPATHIC URTICARIA (CIU)

E.1.1.1

Medical condition in easily understood language

Chronic Itch/Hives without known cause

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10021247
E.1.2	Term	Idiopathic urticaria
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary Objective
•To evaluate the safety of omalizumab compared with placebo in patients with refractory chronic idiopathic urticaria (CIU) receiving concomitant therapy including H1 antihistamines at increased doses (up to four times the approved dose), H2 blockers, and/or leukotriene receptor antagonist (LTRAs)

E.2.2

Secondary objectives of the trial

Secondary Objectives
•To evaluate the efficacy of omalizumab compared with placebo in patients with refractory CIU receiving concomitant therapy including H1 antihistamines at increased doses (up to four times the approved dose), H2 blockers, and/or LTRAs
•To evaluate onset of clinical effect of omalizumab therapy in CIU receiving concomitant therapy including H1 antihistamines at increased doses (up to four times the approved dose), H2 blockers, and/or LTRAs
•To evaluate the quality-of-life benefit of omalizumab therapy in patients with refractory CIU receiving concomitant therapy including H1 antihistamines at increased doses (up to four times the approved dose), H2 blockers, and/or LTRAs

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH XOLAIR (OMALIZUMAB) STUDY Q4883g
Version 1
DATE FINAL: 24 September 2010
The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk. If such genetic hypotheses are identified, they may be tested in future clinical studies within this therapeutic area.

E.3

Principal inclusion criteria

Patients must meet the following criteria for study entry:
1. Aged 12−75 years (age limits may vary dependent upon regional restrictions)
2. Diagnosis of CIU refractory to H1 antihistamines, H2 blockers, and/or LTRAs
at the time of randomization, as defined by all of the following:
The presence of itch and hives for > 6 consecutive weeks at any time prior
to enrollment despite current use of H1 antihistamine (up to four times the
approved dosage), H2 blocker, and/or LTRA treatment during this time period
UAS7 score (range 0−42) ≥ 16 and itch component of UAS7 (range 0−21)
≥ 8 during 7 days prior to randomization (Week 0)
In-clinic UAS ≥ 4 on at least one of the screening visit days (Day −14,
Day −7, or Day 1)
Patients must have been on H1 antihistamine (up to four times the approved
dosage), H2 blocker, and/or LTRA for CIU for at least the 3 consecutive
days immediately prior to the Day −14 screening visit and must document
current use on the day of the initial screening visit.
CIU diagnosis for ≥ 6 months
3. Willing to give written informed consent, adhere to the visit schedules and
meet study requirements
For those patients below the legal age of consent, the child must be willing
to give written informed assent and the parent(s)/guardian(s) must be
willing to give written informed consent.
For patients below the legal age of consent, both child and parent must be
able to adhere to dose and visit schedules and meet study requirements.
4. Willing and able to complete a daily symptom eDiary for the duration of the study
5. Patients must not have any missing eDiary entries in the 7 days prior
to randomization

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will be excluded from study entry:
1. Treatment with an investigational agent within 30 days of Day −14
2. Weight less than 20 kg (44 lbs)
3. Clearly defined underlying etiology for chronic urticarias other than CIU
(main manifestation being physical urticaria). This includes the following urticarias:
Acute, solar, cholinergic, heat, cold, aquagenic, delayed pressure or contact
As well as the following diseases as these diseases may have
symptoms of urticaria or angioedema
Urticarial vasculitis, urticaria pigmentosa, erythema multiforme,
mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia,
or generalized cancer
4. Evidence of parasitic infection defined as having the following three items:
Risk factors for parasitic disease (living in an endemic area,
chronic GI symptoms, travel within the last 6 months to an endemic area
and/or chronic immunosuppression)
AND
An absolute eosinophil count more than twice the upper limit of normal
AND
Evidence of parasitic colonization or infection on stool evaluation for ova
and parasites. Note that stool ova and parasite evaluation will only be
conducted in patients with both risk factors and an eosinophil count more
than twice the upper limit of normal
5. Atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile
pruritus or other skin disease associated with itch
6. Previous treatment with omalizumab within a year prior to Day −14
7. Routine (daily or every other day during 5 or more consecutive days) doses of
the following medications within 30 days prior to Day −14: systemic or
cutaneous (topical) corticosteroids (prescription or over the counter),
hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide
8. IV immunoglobulin G (IVIG), or plasmapheresis within 30 days prior to Day –14
9. Regular (daily/every other day) doxepin (oral) use within 14 days prior to Day −14
10. Patients with current malignancy, history of malignancy, or currently under
work-up for suspected malignancy except non-melanoma skin cancer that
has been treated or excised and is considered resolved
11. Hypersensitivity to omalizumab or any component of the formulation
12. History of anaphylactic shock
13. Presence of clinically significant cardiovascular, neurological, psychiatric,
metabolic or other pathological conditions that could interfere with the
interpretation of the study results and or compromise the safety of the patients
14. Medical examination or laboratory findings that suggest the possibility of
decompensation of co-existing conditions for the duration of the study. Any items
that are cause for uncertainty must be reviewed with the Medical Monitor.
15. Inability to comply with study and follow-up procedures
16. Evidence of current drug or alcohol abuse
17. Nursing women and women of childbearing potential, defined as all women physiologically
capable of becoming pregnant, including women whose career, lifestyle,
or sexual orientation precludes intercourse with a male partner and women
whose partners have been sterilized by vasectomy or other means,
UNLESS they meet the following definition of post-menopausal: 12 months
of natural (spontaneous) amenorrhea or 6 months of spontaneous
amenorrhea with serum FSH levels > 40 mIU/mL or 6 weeks post-surgical
bilateral oophorectomy (with or without hysterectomy) or hysterectomy
OR are using one or more of the following acceptable methods of
contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy),
hormonal contraception (implantable, patch, oral), and double-barrier methods
(any double combination of: IUD, male or female condom with spermicidal gel,
diaphragm, sponge, or cervical cap)
18. Contraindications to diphenhydramine: Overreactivity against the agent
diphenhydramine, other antihistaminic agents, or other components of
this agent; acute bronchial asthma; acute angle-closure glaucoma;
pheochromocytoma; hyperplasia of the prostate gland with formation of
residual urine; epilepsy; hypokalemia; hypomagnesemia; bradycardia;
a congenital long QT syndrome or other clinically significant cardial disorders
(especially coronary heart disease, disturbances in conduction, arrhythmias);
the simultaneous application of drugs which prolong the QT interval
(e.g., antiarrhythmic drugs class IA or III, antibiotics, cisapride, malaria drugs,
antihistaminic drugs, neuroleptic drugs) or lead to hypokalemia
(e.g., certain diuretic drugs); the simultaneous application of MAO inhibitors;
the simultaneous uptake of alcohol

E.5 End points

E.5.1

Primary end point(s)

The primary objective of this study is to evaluate the safety of omalizumab compared with placebo in patients with refractory CIU receiving concomitant therapy including H1 antihistamines at increased doses (up to four times the approved dose), H2 blockers, and/or LTRAs. The safety of omalizumab will be assessed using the following safety outcome measures:
• Incidence and severity of adverse events and serious adverse events
• Changes in vital signs
• Clinical laboratory evaluations
• ATA evaluation at the end of the follow-up period

E.5.1.1

Timepoint(s) of evaluation of this end point

weeks 12, 24 and 40

E.5.2

Secondary end point(s)

1. Change from baseline in weekly itch score (a component of the UAS7) at Week 12

2. Change from baseline in UAS7 at Week 12

3. Change from baseline in weekly hives score at Week 12

4. Time to weekly itch score minimally important difference (MID) response by Week 12

5. Proportion of patients with UAS7 ≤6 at Week 12

6. Change from baseline in weekly largest hive score at Week 12

7. Proportion of weekly itch score MID Responders at Week 12

8. Change from baseline in health-related quality of life as measured by the Dermatology Life Quality Index (DLQI) at Week 12

9. Proportion of angioedema-free days from Week 4 to Week 12 of therapy

E.5.2.1

Timepoint(s) of evaluation of this end point

week 12

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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

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

Information not present in EudraCT

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

Australia

New Zealand

Singapore

Switzerland

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

The end of the study is defined as the last enrolled patient's last visit

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 days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	Yes
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	Yes
F.1.1.6.1	Number of subjects for this age range:	3
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	62
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	15
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	80
F.4.2	For a multinational trial
F.4.2.1	In the EEA	132
F.4.2.2	In the whole clinical trial	321

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

2011-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-05-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-11-22

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials