E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CHRONIC IDIOPATHIC URTICARIA (CIU) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Itch/Hives without known cause |
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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 |
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E.1.3 | Condition being studied is a rare disease | No |
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)
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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
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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. |
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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 |
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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 |
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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
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
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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 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial days | 7 |