E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Atopic Dermatitis or Eczema |
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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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
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 |
The primary objective is to assess the clinical efficacy of repeated subcutaneous (SC) doses of REGN668 in adult patients with moderate-to-severe atopic dermatitis (AD). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include:
• To assess the safety and tolerability of repeated SC doses of REGN668 in this patient population
• To assess the pharmacodynamics (PD) of repeated SC doses of REGN668 in this patient population
• To assess the relationship of AD skin severity, dermatology quality of life (QOL), skin barrier measures, and itch questionnaires to exploratory biomarker analysis |
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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 |
Optional skin punch biopsy samples:
The skin punch biopsy samples will be used to study IL-4Rα, effect of IL-4Rα inhibition with a monoclonal antibody, immunology, inflammation, eosinophil-driven diseases, and atopic diseases in the skin. If necessary, the samples may also be used to identify markers associated with toxicity. The samples will be processed for RNA extraction, histology and immunohistochemistry. RNA samples may be used for exploratory microarray expression profiling or transcriptome sequencing.
Optional genomics sub-study:
The purpose of the genomic analyses is to identify genomic associations with clinical or biomarker response to IL4-Rα inhibition, immunology, inflammation, eosinophil driven diseases, and atopic diseases. This data may be used with data collected from other REGN668 studies to identify genomic markers that may predict response to REGN668 in eosinophilic or atopic diseases. |
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E.3 | Principal inclusion criteria |
1. Male or female, 18 years or older
2. Chronic Atopic dermatitis for at least 3 years
3. History of inadequate rsponse to a stable (> / = 1 month) regimen of topical corticosteroids or calcineurin inhibitors as treatment for Atopic dermatitis within 3 months before the screening visit |
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E.4 | Principal exclusion criteria |
1. Prior treatment with REGN668
2. Presence of certnain laboratory abnormalities at the screening visit
3. Treatment with an investigational drug within 8 weeks
4. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
5. Certain treatments and medical procedures, underaken within a particular timeframe prior to the baseline visit, preclude eligibility for participation in the study
6. Known history of human immunodeficiency virus (HIV) infection
7. History of malignancy within 5 years before the baseline visit, with certain exceptions
8. Planned surgical procedure dirung the length of the patient's participation in this study
9. History of clinical parasite infection
10. Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor’s medical monitor, would place the patient at risk, interfere with participation in the study, or interfere with the interpretation of study results
11. Pregnant or breast-feeding women
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the percent change in Eczema Area and Severity Index (EASI) score from baseline to week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the duration of the study |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include:
• Proportion of patients who achieve an Investigator’s Global Assessment (IGA) score of 0 or 1 at week 12
• Proportion of patients who achieve ≥50% overall improvement in EASI score from baseline to week 12 (achieving an EASI 50 [50% or greater improvement in EASI score]) is considered by dermatology investigators a clinically significant level of improvement to use as an endpoint.
• Change in EASI score from baseline to week 12
• Change (or percent change) in IGA score from baseline to week 12
• Change in % body surface area (BSA), SCORing Atopic Dermatitis (SCORAD) score, Pruritus numerical rating scale (NRS), 5-D Pruritus scale or Quality of Life Index for Atopic Dermatitis (QOLIAD) from baseline to week 12
• Incidence of treatment-emergent adverse events (TEAEs) from baseline through week 20 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the duration of the study |
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Quality of Life |
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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) | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |