E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Part B: Moderate to Severe Atopic Dermatitis |
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E.1.1.1 | Medical condition in easily understood language |
Atopic Dermatitis / 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 | 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 |
Part A of the study is to characterize the safety and pharmacokinetics (PK) of dupilumab administered as a single dose in pediatric patients, 6 months to less than 6 years of age with severe atopic dermatitis (AD).
Part B of the study is to demonstrate the efficacy of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with topical corticosteroids (TCS) in pediatric patients, 6 months to less than 6 years of age, with moderate-to severe AD. |
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E.2.2 | Secondary objectives of the trial |
Part A of the study is to evaluate the efficacy and immunogenicity of a single dose of dupilumab in patients 6 months to less than 6 years of age with severe AD.
Part B is to assess the safety and immunogenicity of multiple doses of dupilumab over 16 weeks of treatment when administered concomitantly with TCS in patients 6 months to less than 6 years of age with moderate-to-severe AD.
Other Objectives (Part B)
- To assess the concentrations of dupilumab in serum following repeated subcutaneous (SC) dosing.
- To assess the effects of dupilumab on blood and skin biomarkers of inflammation in comparison with placebo.
- To study dupilumab’s mechanism of action (related to efficacy and/or safety), why some patients respond better than others (safety and/or efficacy), type 2 inflammation, as well as AD and related diseases. |
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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 |
1. Pharmacogenomic sub-study
2. Vaccine sub-study (for Part B only)
3. Tape stripping sub-study (for Part B only) |
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E.3 | Principal inclusion criteria |
1. Diagnosis of atopic dermatitis (AD) according to the American Academy of Dermatology consensus criteria at the screening visit
2. Patients with documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s)
3. IGA score at screening and baseline visits
a. part A: IGA = 4
b. part B: IGA ≥3
4. EASI score at screening and baseline visits
a. part A: EASI ≥21
b. part B: EASI ≥16
5. Body Surface Area (BSA) involvement at screening and baseline visits
a. part A: ≥15%
b. part B: ≥10%
6. At least 11 (of a total of 14) applications of a topical emollient (moisturizer) during the 7 consecutive days immediately before the baseline visit (not including the day of randomization) (for part B of the study only)
7. Baseline worst scratch/itch score weekly average score for maximum scratch/itch intensity ≥4 (for part B of the study only)
8. At least 11 (of a total of 14) daily applications of low potency TCS during the 2-week TCS standardization period (beginning on day -14) leading up to the baseline visit (for part B of the study only). |
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E.4 | Principal exclusion criteria |
1.Prior treatment with dupilumab.
2. History of important side effects of low potency topical corticosteroids (only applicable for part B of the study)
3. Having used immunosuppressive/immunomodulating drugs within 4 weeks before the baseline visit
4. Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit
5. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit.
6. Known or suspected immunodeficiency, known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit, established diagnosis of HBV infection or HBV seropositivity at screening, established diagnosis of HCV infection or HCV seropositivity at screening
7. History of malignancy at any time before the baseline visit.
8. Diagnosed active endoparasitic infections or at high risk of these infections
9. Severe concomitant illness(es) that, in the investigator's judgment, would adversely affect the patient's participation in the study.
10. Body weight <5 kg or ≥30 kg at baseline (only applicable part B of the study). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A:
1. Concentration of total dupilumab in serum over time and pharmacokinetic (PK) parameters
2. The incidence and severity of treatment-emergent adverse events (TEAEs) through the end of part A.
Part B:
1. The proportion of patients with an Investigator Global Assessment (IGA) score of 0 to 1
2. For European Medicines Agency - EMA only: Proportion of patients with Eczema Area and Severity Index (EASI) -75 (≥75% improvement from baseline)
3. For EMA only: Proportion of patients with an IGA score of either 0 or 1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A:
Ad 1: To week 4
Ad 2: To week 4
Part B:
Ad 1: Week 16
Ad 2: Week 16
Ad 3: Week 16 |
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E.5.2 | Secondary end point(s) |
Part A:
1. The incidence of serious adverse events (SAEs)
2. The incidence of severe TEAEs
3. Percent change in EASI score from baseline to week 4
4. Percent change in SCORing Atopic Dermatitis (SCORAD)
5. Proportion of patients with an IGA score of either 0 or 1
6. Determine immunogenicity titer
Part B:
1. Not applicable for EMA: Proportion of patients with EASI-75 (≥75% improvement from baseline)
2. Percent change in EASI score
3.Percent change from baseline to week 16 in weekly average of daily worst scratch/itch NRS score
4. Proportion of patients with EASI-50
5. Proportion of patients with EASI-90
6. Change in percent Body Surface Area (BSA) affected by AD
7. Percent change in SCORAD
8. Change from baseline to week 16 in weekly average of daily worst scratch/itch NRS score
9. Proportion of patients with improvement (reduction) of weekly average of daily worst scratch/itch NRS score ≥4 from baseline at week 16
10. Proportion of patients with improvement (reduction) of weekly average of daily worst scratch/itch NRS score ≥3 from baseline at week 16
11. Change from baseline to week 16 in skin pain NRS
12. Change from baseline to week 16 in sleep quality NRS
13. Change from baseline to week 16 in health-related quality of life, as measured by CDLQI (patients ≥4 years of age) and IDQOL (patients <4 years of age)
14. Change in Dermatitis Family Index (DFI)
15. Change in Patient Oriented Eczema Measure (POEM)
16. Topical treatment for AD – proportion of TCS medication-free days
17. Mean weekly dose of low potency Topical corticosteroids
18. Mean of caregiver missed workdays
19. Incidence of skin infection TEAEs
20. Incidence of SAEs through week 16 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Part A:
Ad 1: Baseline to week 4
Ad 2: Baseline to week 4
Ad 3: Baseline to week 4
Ad 4: Baseline to week 4
Ad 5: At week 4
Ad 6: To week 4
Part B:
Ad 1: At week 16
Ad 2: From baseline to week 16
Ad 3: At week 16
Ad 4: At week 16
Ad 5: At week 16
Ad 6: From baseline to week 16
Ad 7: From baseline to week 16
Ad 8: From baseline to week 16
Ad 9: From baseline to week 16
Ad 10: From baseline to week 16
Ad 11: From baseline to week 16
Ad 12: From baseline to week 16
Ad 13: From baseline to week 16
Ad 14: From baseline to week 16
Ad 15: From baseline to week 16
Ad 16: From baseline to week 16
Ad 17: To week 16
Ad 18: From baseline to week 16
Ad 19: To week 16
Ad 20: To week 16 |
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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 | Yes |
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 |
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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) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Single ascending-dose, Sequential cohort study staggered by age |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 Kingdom |
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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Last visit of last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |