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 |
Chronic spontaneous urticaria (CSU) is a distressing skin condition that causes red, swollen, itchy and sometimes painful hives or “wheals” on the skin. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
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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 test the hypothesis that treatment with LY3454738 is superior to placebo as measured
by patient-assessed itch severity and hive count for the treatment of adult participants with CSU |
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E.2.2 | Secondary objectives of the trial |
- To compare the efficacy of LY3454738 to placebo as measured by improvement in signs and symptoms of CSU
- To characterize the pharmacokinetics (PK) of LY3454738 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
--Are male or female participants from 18 to 65 years of age, inclusive, at the time of
signing the informed consent document.
--Have a diagnosis of CSU for at least 6 months before the screening visit.
--Are taking an approved 24-hour oral dose of a second-generation H1-antihistamine for CSU for at least 10 consecutive days before the baseline visit, and agree to continue taking this medication at the same dose every day throughout the study.
--Have an urticaria activity score during a 7-day period (UAS7 score) of 16 or more during the 7 consecutive days prior to the baseline visit.
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E.4 | Principal exclusion criteria |
--Have a clearly defined underlying cause for chronic urticaria other than
CSU. Such causes can include, but are not limited to, the following:
symptomatic dermatographism (urticaria factitia); cold-, heat-, solar-,
pressure-, delayed pressure-, aquagenic-, cholinergic-, or contacturticaria.
--Have diseases, other than chronic urticaria, with urticarial or
angioedema symptoms. These diseases include, but are not limited to,
urticarial vasculitis, urticaria pigmentosa, erythema multiforme,
mastocytosis, hereditary, or acquired angioedema (for example, due to
C1 inhibitor deficiency), lymphoma, leukemia, or generalized
malignancy.
--Have any other skin disease associated with chronic itching that, in the
investigator's opinion, might influence the study evaluations and results
(including, but not limited to, prurigo nodularis, atopic dermatitis,
bullous pemphigoid, dermatitis herpetiformis, and senile pruritus).--
Have a current or recent acute, active infection.
--Have had, within 6 months of screening, any of the following types of
infection:
Serious infections (requiring hospitalisation, and/or IV or equivalent
intravenous antibiotic treatment),
Opportunistic infections
Chronic infections (duration of symptoms, signs, and/or treatment of 6
weeks or longer),
Recurring infection (including, but not limited to, herpes simplex, herpes
zoster, recurring cellulitis, chronic osteomyelitis).
--Have human immunodeficiency virus (HIV) infection.
--Have a current or past infection with hepatitis B virus (HBV) (that is,
positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core
antibody)
--Have a current infection with hepatitis C virus (HCV) (that is, positive
for HCV ribonucleic acid [RNA]) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change in UAS7 score from baseline to Week 12 in Period 2, defined as the Week 12 UAS7 score minus the baseline UAS7 score. |
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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) |
--Change from baseline in ISS7 at Week 12 is the Week 12 ISS7 score minus the baseline ISS7 score.
--Change from baseline in HSS7 at Week 12 is the Week 12 HSS7 score minus the baseline HSS7 score.
--The proportions of participants who achieve a UAS7 score ≤6 at Week 12 will be presented for each treatment group. Participants will be classified as nonresponders at Week 12 (that is, did not achieve UAS7 ≤6 at Week 12) if they have a missing UAS7 score at Week 12. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Germany |
Poland |
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
|
A participant is considered to have completed the study if he or she has completed all required phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Activities. The end of the study is defined as the date of the last visit or last scheduled procedure shown in the Schedule of Activities for the last participant in the trial globally. |
|
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 | 6 |
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 | 9 |