E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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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 compare the clinical efficacy of benralizumab with placebo in patients with AD despite treatment with topical medications |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of benralizumab with placebo on supportive measures of clinical efficacy in patients with AD despite treatment with topical medications. To compare benralizumab with placebo on patient-reported health-related quality of life measures in patients with AD despite treatment with topical medications. To estimate the PK and immunogenicity of benralizumab in in patients with AD despite treatment with topical medications. To compare long-term treatment of 2 benralizumab dosing regimens up to Week 52 in patients with AD despite treatment with topical medications. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female participants ≥ 12 years of age at the time of signing the ICF. 2. Participants weighing ≥ 35 kg at the time of signing the ICF. 3. Physician-confirmed diagnosis of AD (according to American Academy of Dermatology Consensus Criteria) that is not adequately controlled with topical medications. 4. EASI score of ≥ 12 at screening and ≥ 16 at randomization. 5. IGA score of ≥ 3 (on a scale of 0 to 4, in which 3 is moderate and 4 is severe) at screening and at randomization. 6. AD involvement of ≥ 8% body-surface area at screening and ≥ 10% body-surface area at randomization. 7. A pruritus numerical rating scale average score for maximum itch intensity of ≥ 4, based on the average of daily pruritus numerical rating scale scores for maximum itch intensity reported during the 7 days prior to randomization. 8. Documented recent history (within 6 months prior to screening) of inadequate response to treatment with topical medications, or patients for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks). 9. Participants that have applied a stable dose of topical emollient (moisturizer) twice daily for ≥ 7 consecutive days immediately before the randomization visit. (NOTE: See exclusion criterion 23 for limitations regarding emollients) 10. Participants must be willing and able to complete daily PRO assessments: (a) Complete at least 70% of daily PRO assessments between Visit 1 and Visit 2 and (b) Complete at least 5 of 7 daily PRO assessments in the 7 days prior to Visit 2. |
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E.4 | Principal exclusion criteria |
1. Participants with active dermatological conditions (eg, psoriasis, seborrheic dermatitis, cutaneous lymphoma) other than AD that, in the investigator’s opinion, may interfere with the study assessments. 2. Known active allergic or irritant contact dermatitis that, in the investigator’s opinion, may interfere with the study assessments. 3. Current malignancy, or history of malignancy, with the exception of: (a) Participants who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent/assent, was obtained. (b) Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent/assent, was obtained. 4. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the participant throughout the study. (b) Influence the findings of the studies or their interpretations. (c) Impede the participant’s ability to complete the entire duration of study. 5. History of anaphylaxis to any biologic therapy or vaccine. 6. History of Guillain-Barré syndrome. 7. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent/assent is obtained that has not been treated with, or has failed to respond to standard of care therapy. 8. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete entire duration of the study. 9. Current active liver disease: (a) Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen or hepatitis C antibody), or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis. (b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 3 times the upper limit of normal, confirmed by repeated testing during the run-in period. 10. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test. 11. Participants who have received treatment for AD with TCS, topical calcineurin inhibitors (TCI), or topical phosphodiesterase-4 (PDE4) inhibitors within the 7 days prior to the randomization visit. 12. Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (patients may continue using stable doses of such moisturizers if initiated before the screening visit). 13. Regular use (2 visits per week) of a tanning booth/parlor or phototherapy for AD within 4 weeks prior to the randomization visit. 14. Use of immunosuppressive medication (including but not limited to: Janus kinase inhibitors, methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent/assent is obtained. 15. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent/assent is obtained. 16. Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to the date informed consent/assent is obtained, whichever is longer. 17. Receipt of live attenuated vaccines 30 days prior to first dose of IP. 18. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent/assent is obtained, whichever is longer. 19. Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior to the date of informed consent/assent and anticipated changes in immunotherapy throughout the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
A binary response giving the proportion of patients with an IGA 0/1 and a decrease in IGA of ≥ 2 points at Week 16 relative to baseline. |
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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) |
Key secondary endpoints: - proportion of patients with skin clearance (EASI-75) at Week 16 - proportion of patients with an improvement of ≥ 4 or more points in peak pruritus weekly score at Week 16 - proportion of patients with skin clearance (EASI-90) at Week 16 For other secondary endpoints, please refer to the Protocol. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
various time points as defined in the 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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | 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 | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
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 | 32 |
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 |
Bulgaria |
Czech Republic |
France |
Korea, Republic of |
Poland |
Spain |
United States |
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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
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 2 |