E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic spontaneous urticaria |
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E.1.1.1 | Medical condition in easily understood language |
spontaneous occurrence of daily, or almost daily, hives and itching for at least 6 weeks without an obvious 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 | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072757 |
E.1.2 | Term | Chronic spontaneous 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 |
Evaluate the proportion of patients achieving disease control (urticaria control test [UCT] score of greater than or equal to 12) at Week 12 in adult patients with CSU with inadequate response to H1 antihistamine treatment and treated by omalizumab 300 mg S.C. every 4 weeks |
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E.2.2 | Secondary objectives of the trial |
• To assess the extent to which omalizumab 300 mg S.C. controls CSU after 12 weeks of treatment using the UCT score, with or without the presence of angioedema.
• To assess the effect of omalizumab 300 mg S.C. on QoL after 12 weeks of treatment using the chronic urticaria quality of life (CU-QoL) questionnaire; the angioedema quality of life (AE-QoL) questionnaire and the dermatology life quality index (DLQI).
• To assess the effect of omalizumab 300 mg S.C. on CSU disease activity after 12 weeks of treatment using the urticaria activity score (UAS7).
• To assess the effect of omalizumab 300 mg S.C. on angioedema activity after 12 weeks of treatment using the angioedema activity score (AAS). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients aged between 18 and 75 years.
2.Diagnosis of CSU for ≥ 6 months and an inadequate response to nsH1 antihistamines at the time of the request, as defined by the following:
•The presence of itch and hives for > 6 consecutive weeks at any time prior to enrollment, despite current use of H1 antihistamine therapy during this time period.
•Weekly UAS7 score (range 0 to 42) 16 and UCT score (range 0 to 16) < 8 prior to enrollment (Day 1).
3.Patients must document current use of an H1 antihistamine for CSU on the day of the initial visit and Day 1.
4.Willing and able to complete a daily symptom diary (paper) for the duration of the study.
5.Willing to give written informed consent, adhere to the visit schedules and meet clinical requirements. |
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E.4 | Principal exclusion criteria |
1.Treatment with an investigational agent within 30 days before enrollment.
2.Body weight less than 40 kg.
3.Clearly defined underlying etiology for chronic urticaria other than CSU (main manifestation being physical urticaria). This includes the following urticaria types: acute, solar, cholinergic, heat, cold, aquagenic, delayed pressure or contact urticaria, or skin disease that includes urticarial plaques (other than CSU) such as bullous pemphigoid, dermatitis herpetiformis.
4.The following diseases which may have symptoms of urticaria or angioedema: urticarial vasculitis, urticaria pigmentosa, erythema multiform, mastocytosis, hereditary or acquired angioedema, lymphoma, leukemia, generalized cancer.
5.Evidence of parasitic infection defined as having the following three items:
•Risk factors for parasitic disease (living in an endemic area, chronic gastrointestinal 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 (ULN).
AND
•Evidence of parasitic colonization or infection in 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 ULN.
6.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.
7.Concomitant use of cyclosporine or any other immunosuppressive agent.
8.Hypersensitivity to omalizumab or any component of the formulation.
9.History of anaphylactic shock.
10.Presence of clinically significant cardiovascular, neurological, psychiatric, metabolic or other pathological conditions that could compromise the safety of the patients.
11.Medical examination or laboratory findings that suggest the possibility of decompensation of co-existing conditions. Any items that are cause for uncertainty must be reviewed with the attending physician.
12.Inability or unwillingness to comply with the visits and follow-up procedures.
13.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and for 16 weeks after stopping treatment.
14.Routine (daily or every other day during 5 or more consecutive days) doses of the following medications within 30 days prior to Day -7: systemic or cutaneous (topical) corticosteroids (prescription or over the counter), hydroxychloroquine, methotrexate, cyclosporine, or cyclophosphamide.
15.Intravenous (i.v.) immunoglobulin G or plasmapheresis within 30 days prior to Day -7
16.Regular (daily/every other day) doxepin (oral) use within 14 days prior to Day -7.
17.Any H2 antihistamine use within 7 days prior to Day -7.
18.Any leukotriene receptor antagonist (LTRA) (montelukast or zafirlukast) within 7 days prior to Day 7.
19.Evidence of current drug or alcohol abuse.
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the proportion of patients achieving disease control (urticaria control test [UCT] score of greater than or equal to 12) |
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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) |
• To evaluate the UCT score changes, with or without the presence of angioedema.
• To evaluate the change from baseline of chronic urticaria quality of life (CU-QoL) questionnaire; the angioedema quality of life (AE-QoL) questionnaire and the dermatology life quality index (DLQI).
• To evaluate the change from baseline of urticaria activity score (UAS7).
• To evaluate the change from baseline of the angioedema activity score (AAS). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 25 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
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LVLS
OR
The study can be terminated at any time for any reason by Novartis. Reasons for terminating the study may include, but are not limited to, the following:
•The incidence or severity of AEs in this or other studies indicates a potential health hazard to patients.
•Patient enrollment is unsatisfactory.
•Data recording is inaccurate or incomplete
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |