| 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 | 14.0 | | 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 | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | Primary Objective
?To evaluate the efficacy of omalizumab compared with placebo in patients with refractory chronic idiopathic urticaria (CIU) receiving concomitant H1 antihistamine therapy | |
| E.2.2 | Secondary objectives of the trial | Secondary Objectives
? To evaluate the safety of omalizumab therapy in patients with refractory CIU
? To evaluate onset of clinical effect of omalizumab therapy in CIU
? To evaluate the dose of omalizumab therapy in patients with refractory CIU
? To evaluate duration of response after withdrawal of omalizumab in patients with refractory CIU
? To evaluate the quality-of-life benefit of omalizumab therapy in patients with refractory CIU | |
| 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 Q4882g
Date : 24 September 2010
Version 1
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 at the time of randomization,
as defined by all of the following:
The presence of itch and hives for ? 8 consecutive weeks at any time prior
to enrollment despite current use of H1 antihistamine 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 an approved dose of an H1 antihistamine 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 willingto 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. Any H2 antihistamine use within 7 days prior to Day ?14.
11. Any LTRA (montelukast or zafirlukast) within 7 days prior to Day ?14.
12. Any H1 antihistamines at greater than approved doses within 3 days prior to
Day ?14.
13. 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.
14 .Hypersensitivity to omalizumab or any component of the formulation.
15. History of anaphylactic shock.
16. 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.
17. 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.
18. Inability to comply with study and follow-up procedures.
19. Evidence of current drug or alcohol abuse.
20. Nursing women or 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).
21. 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 efficacy endpoint is the change in weekly itch score from baseline to Week 12. The analysis of the primary endpoint will consist of treatment comparisons made using analysis of covariance (ANCOVA) controlling for baseline weekly itch score, and baseline weight (less than 80 kg vs. more than or equal to 80 kg). The ANCOVA model will be based on the mITT patients. Missing Week 12 itch scores will be imputed by carrying forward the patients? baseline scores (BOCF). The Week 12 itch scores for patients who received excluded therapy listed in Section 4.4.2 by Week 12 will also be imputed using their baseline scores. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | |
| E.5.2 | Secondary end point(s) | 1. Change from baseline in UAS7 at Week 12
2. Time to weekly itch score MID response by Week 12
3. Proportion of patients with UAS7 ?6 at Week 12
4. Change from baseline in weekly hive score at Week 12
5. Change from baseline in weekly largest hive score at Week 12
6. Proportion of weekly itch score MID responders at Week 12
7. Proportion of patients with UAS7 ?6 at Week 28
8. Change from baseline in health-related quality-of-life as measured by the 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 | |
| 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 | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| 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 | Yes |
| 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 | 4 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 24 |
| 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 | | Russian Federation | | Turkey | | 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
