| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Spontaneous Urticaria |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic Spontaneous Urticaria |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| 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 |
|
| 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 evaluate the effect of tezepelumab on improvement in the Urticaria Activity Score over 7 days (UAS7)
|
|
| E.2.2 | Secondary objectives of the trial |
•To evaluate the effect of tezepelumab on :
•compared with placebo in CSU subjects using the UAS7
• improvement in itch using the Itch Severity Scoreover 7 days (ISS7)
•improvement in hives using the Hives Severity Score over 7 days (HSS7)
•subjects achieving minimal residual disease using the UAS7
•subjects achieving the minimal important difference (MID) on change from baseline in the UAS7
• on complete resolution of itch using the ISS7
•on subjects achieving the MID on change from baseline in the ISS7
•on the complete resolution of hives using the HSS7
•on subjects achieving the MID on change from baseline in the HSS7
• sleep interference and quality (falling asleep, nighttime awakenings, restfulness upon awakening)
• improvement in urticaria disease control using the Urticaria Control Test (UCT)
• angioedema using the Angioedema Activity Score over 7 days (AAS7)
• the cumulative time period that treated subjects are angioedema occurrence-free using the AAS7
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Subject has been informed about study procedures and medications
and has provided informed consent prior to initiation of any studyspecific
activities/procedures
•Subject is able to communicate with the investigator, and understands
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and complies with the requirements of the study
•Age ≥ 18 to ≤ 80 years of age at screening
•Chronic spontaneous urticaria diagnosis for ≥ 6 months at the time of
screening visit 1
•CSU inadequately controlled by sgAH at enrollment, as defined by all of
the following:
-The presence of itch and hives for ≥ 6 consecutive weeks at any time
prior to screening visit 2
-Failure to respond to an sgAH (up to 4 times the approved dose)
-Urticaria Activity Score over 7 days (UAS7) (range 0-42) ≥ 16 and Hives
Severity Score over 7 days (HSS7) (range 0-21) ≥ 8 during the 7 days
prior to enrolment
•Subject must have been on a sgAH at approved or increased doses (up
to 4x the approved dose) for treatment of CSU for at least 3 consecutive
days immediately prior to the day -14 screening visit (screening visit2)
and must have documented current use on the day of screening visit 1
•This is only applicable for anti-IgE experienced subjects. Subject with
CSU who discontinued, is intolerant to, or was an inadequate responder
to anti-IgE therapies despite being treated with omalizumab 300 mg
Q4W for 6 months or higher doses of omalizumab > 2 months (or per
local country treatment standards) or another anti-IgE therapy. |
|
| E.4 | Principal exclusion criteria |
Disease Related:
•Urticaria is solely due to inducible urticaria
•Active dermatologic diseases (or conditions) other than chronic
urticaria, with urticaria wheals or angioedema symptoms such as
urticarial vasculitis, erythema multiforme, cutaneous mastocytosis
(urticaria pigmentosa) and hereditary or acquired angioedema (eg, due
to C1 inhibitor deficiency)
•Any other active skin disease associated with chronic itching that might
influence,in the investigator's opinion, the study evaluations and results
(eg, atopic dermatitis, dermatitis herpetiformis, senile pruritus, etc.)
•History of a clinically significant infection within 28 days prior to day 1
that, in the opinion of the investigator or medical monitor, might
compromise the safety of the sub. in the study, interfere with
evaluation of the investigational product, or reduce the subject's ability
to participate in the study. Clinically significant infections are defined as
either of the following:
1)a systemic infection; or
2)a serious skin infection requiring parenteral antibiotic, antiviral, or
antifungal medication
•Diagnosis of a helminth parasitic infection within 6 months prior to
screening visit 1 that had not been treated with or had failed to respond
to standard of care therapy
•Documented medical history of chronic alcohol or drug abuse within 12
months prior to screening visit 1
•Evidence of active liver disease at screening, including jaundice or
aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
alkaline phosphatase greater than twice the upper limit of normal (ULN)
•Sub. who, in the opinion of the investigator, have evidence of
active tuberculosis (TB), either treated or untreated, or a positive
purified protein derivative (PPD) or QuantiFERON-tuberculosis Gold Plus
(QFT-Plus) test for TB during screening. Sub. with an indeterminate
QFT-Plus may be enrolled if they have ALL of the following:
-No symptoms of TB: productive, prolonged cough (> 3 weeks);
coughing up blood; fever; night sweats; unexplained appetite loss;
unintentional weight loss
-No evidence of active TB on chest radiograph within 3 months prior to
the first dose of investigational product. Note: Chest radiograph is not
part of screening procedure and will be the responsibility of the
Investigator as this is outside the scope of this protocol
Note: If required, QFT-plus test can be repeated, Sub. with the
repeated indeterminate QFT-plus should be excluded from the study.
•History of malignancy, except for basal cell carcinoma or in situ
carcinoma of the cervix treated with apparent success with curative
therapy≥12 months prior to screening or other malignancies treated
with apparent success with curative therapy ≥ 5 years prior to screening
visit 1
•Sub. is unable to complete an electronic patient diary or complete
questionnaires, or does not meet the required level of compliance with
the eDiary during 14 days sgAH stabilization period
-Completion of UAS (daily) for <11 of 14 days prior to randomization
-Completion of AAS (daily) for <11 of 14 days prior to randomization
Other Medical Conditions
•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 and
approved by the Medical Monitor
•History or evidence of severe depression, schizophrenia, previous
suicide attempts, or suicidal ideation
Prior/Concomitant Therapy
•Treatment with any biologic products (eg, omalizumab, ligelizumab)
within 4 months or 5 half-lives (whichever is longer) prior to screening
visit 1
•Routine (daily or every other day for 5 or more consecutive days) use of
systemic corticosteroids within 30 days prior to screening visit 1
•Routine (daily or every other day for 5 or more consecutive days) use of
systemic hydroxychloroquine within 30 days prior to screening visit 1
•Routine (daily or every other day for 5 or more consecutive days) use of
methotrexate, cyclosporine A, cyclophosphamide, tacrolimus,
azathioprine,and mycophenolate mofetil within 30 days prior to
screening visit 1
•Undergone plasmapheresis within 30 days prior to screening visit 1
•Major surgery within 8 weeks prior to screening visit 1 or planned
inpatient surgery or hospitalization during the study period
•Receipt of Ig or blood products within 30 days prior to screening visit 1
•Regular (daily or every other day) treatment with oral doxepin within
14 days prior to screening visit 1
•Vacc. with a live or attenuated vaccine within 30 days prior to
screening visit 1. Receipt of COVID-19 vaccines and inactive/killed
vacc. (eg, inactive influenza) are allowed, provided the
vacc. are not adminis. within 7 days before or after any
study, dosing visit
•Known hypersensitivity, including severe hypersensitivity reactions
and/or history of anaphylactic shock, to omalizumab or any ingredient of
Xolair |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline in UAS7 at week 16 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Change from baseline in ISS7 at week 16
• Change from baseline in HSS7 score at week 16
• UAS7 ≤ 6 at week 16
• Change from baseline in UAS7 ≤ 10 at week 16
• Complete response in UAS7
defined as UAS7 = 0 at week 16
• ISS7 = 0 at week 16
• Change from baseline in ISS7 ≤ 5 at week 16
• HSS7 = 0 at week 16
• Change from baseline in HSS7 ≤ 5.5 at week 16
• Change from baseline in sleep interference score at week 16
• Change from baseline in the sleep interference and quality diary items
at week 16
• Change from baseline UCT score at week 16
• Change from baseline in AAS7 at week 16
• Cumulative weeks that subjects achieve AAS7 = 0 responses between
baseline and week 16
• Change from baseline in the CU-Q2oL at week 16
• Change from baseline in DLQI at week 16
• Change from baseline in the AE-QoL at week 16
• Change from baseline in the AECT score at week 16
• Complete control in AECT (AECT = 16) at week 16
• Change from baseline in WPAI-CU score at week 16
• Cumulative frequency of H1-antihistamine rescue medication
utilization from baseline to week 16
• Serum concentrations of tezepelumab at scheduled visits
• Subject incidence of adverse events (including serious adverse
events) |
|
| 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 | 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) | 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 | 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) | Yes |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| 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 |
| Canada |
| Japan |
| United States |
| France |
| Germany |
| Greece |
| Italy |
| Poland |
| Spain |
| Korea, Republic of |
|
| 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
|
|
| 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 | 10 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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