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 |
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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 | 18.1 |
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 |
To establish the dose-response relationship of QGE031 with respect to achievement of complete hives response at Week 12 in patients with CSU when added to H1-AH alone or in
combination with H2-AH and/or a LTRA |
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E.2.2 | Secondary objectives of the trial |
Evaluate efficacy of QGE031 compared to omalizumab 300 mg with respect to achievement of complete hives response
at Week 12
evaluate the efficacy of individual QGE031 doses of 24 mg, 72 mg and 240 mg s.c. compared to omalizumab 300 mg with respect to achievement of complete hives response
at Week 20
Evaluate the efficacy of QGE031 doses of 24 mg, 72 mg and 240 mg s.c. versus placebo and omalizumab 300 mg:
Change from Baseline in Hives Severity Score (HSS7)
Change from Baseline in Itch Severity Score (ISS7)
Change from Baseline in Urticaria Activity Score (UAS7)
Evaluate the safety (including immunogenicity) and tolerability of QGE031 (doses of 24 mg, 72 mg and 240 mg s.c. every 4 weeks) versus placebo and omalizumab 300 mg |
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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 |
Biomarker substudy: Serum samples, plasma samples and urine samples will be collected for the analysis of soluble biomarkers related to the disease, pathway of QGE031 or
effect of treatment. Exploratory pharmacogenetic substudy: Planned as part of this study to examine whether individual genetic variation in genes relating to drug metabolism, CSU, and the drug target pathway confer differential responses to QGE031.
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E.3 | Principal inclusion criteria |
-Male and female adult patients aged ≥ 18 to ≤ 75 years.
-Diagnosis of CSU (with or without urticarial dermographism when testing for dermographism) refractory to H1-AH at approved or increased doses alone, or in combination with H2-AH and/or leukotriene receptor antagonist (LTRA) 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-AH (up to four times the approved dosage), or in combination with H2-AH and/or LTRA treatment during this time period
- UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1)
- 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-AH at approved or increased doses (up to fourfold) alone or in combination with H2-AH and/or a LTRA for treatment of CSU for at least the 3 consecutive days immediately prior to the Day -14 screening visit and must have documented current use on the day of the initial screening visit
- CSU diagnosis for ≥ 6 months
-Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules.
- Patients must not have had any missing eDiary entries in the 7 days prior to randomization. Re-screening may be considered. |
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E.4 | Principal exclusion criteria |
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lifes prior to Visit 1, whichever is longer.
History of hypersensitivity to any of the study drugs or its components, or to drugs of similar chemical classes.
Clearly defined underlying etiology for chronic urticarias other than CSU.
This includes the following:
Inducible urticaria: urticaria factitia, cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g.,due to C1 inhibitor deficiency)
Patients with a stool examination positive for ova or parasites (at screening); re-screening may be considered if a repeat stool examination is negative following treatment.
Any other skin disease associated with chronic itching that might confound the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus etc.)
Previous exposure to omalizumab or QGE031
History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to randomization
Inability to comply with study and follow-up procedures
Use of prohibited treatment detailed in protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Achieving complete hives response at Week 12. Complete hives response is defined as a HSS7 score of 0. Analogously, complete itch response and complete UAS7 response are defined as an ISS7 and UAS7 score of 0, respectively. |
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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) |
Evaluate the efficacy of QGE031 based on the selected dose response model compared to omalizumab 300 mg with respect to achievement of complete hives response.
Evaluate the efficacy of individual QGE031 doses of 24 mg, 72 mg and 240 mg s.c. compared to omalizumab 300 mg with respect to achievement of complete hives response
Evaluate the efficacy of QGE031 doses of 24 mg, 72 mg and 240 mg s.c. versus placebo and omalizumab 300 mg in patients with CSU, in terms of:
Change from Baseline in Hives Severity Score (HSS7)
Change from Baseline in Itch Severity Score (ISS7)
Change from Baseline in Urticaria Activity Score (UAS7)
evaluate the safety (including immunogenicity) and tolerability of
QGE031 versus placebo and omalizumab 300 mg in patients with CSU particularly in regards to
ECG
adverse events
vital signs
and clinical laboratory |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at Week 12 and Week 20 (as indicated in protocol) |
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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 | 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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 | No |
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 |
Canada |
Germany |
Greece |
Japan |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
United States |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |