E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Part 2: Atopic Dermatitis (AD)
Part 3: Netherton Syndrome (NS) |
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E.1.1.1 | Medical condition in easily understood language |
AD:Skin disease with severe itching, redness, scaling & sometimes oozing and crusting.
NS:Hereditary condition with hair shaft abnormality, scaling skin disorder & signs of hypersensitivity syndrome. |
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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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062909 |
E.1.2 | Term | Netherton's syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Demonstrate tolerability (systemic and local) of repeated daily topical applications of BPR277 ointment in adult HV subjects and patients with AD and NS (all parts).
• In Part 2, evaluate whether BPR277 1% ointment b.i.d. maintains a treatment effect, induced by topical corticosteroids, by assessing that TLSS increase is at most half of that of its vehicle in AD patients.
• In Part 3A, assess the potential of BPR277 1% ointment b.i.d. to improve the clinical severity of lesional skin (TLSS-NS) in the majority of NS patients at end of treatment versus baseline of ≥ 2 points.
• In Part 3 (cohorts AA & AB), assess the potential of BPR277 (1% ointment, applied either b.i.d. or q.d.) to improve the clinical severity of lesional skin (TLSS-NS) in NS patients. |
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E.2.2 | Secondary objectives of the trial |
• Evaluate systemic steady state pharmacokinetics in human after topical administration of BPR277 ointment.
• Determine BPR277 concentrations in the skin and the urinary excretion of BPR277 after repeated topical administration of BPR277 ointment in adult HV subjects and patients with AD and NS (for NS only in Part 3A).
• Assess the ability of repeated topical applications of BPR277 to restore the skin barrier function in AD and NS patients as demonstrated by the change in Transepidermal Water Loss (TEWL) and skin capacitance (Part 2/3A). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible for inclusion in this study have to fulfill all of the following criteria:
Part 1 (healthy volunteers)
• Healthy male and female subjects of non childbearing potential, 18 to 65 years of age inclusive and in good health
Part 2 (patients with atopic dermatitis):
• Male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
• Presence of atopic dermatitis confirmed by Itchy skin condition in the past 12 months (must have) Plus three or more of the following:
a. History of involvement of the skin creases
b. Personal history of asthma or hay fever
c. History of generally dry skin in the past year
d. Onset before age of 2 years
e. Visible flexural dermatitis
• Diagnosis of at least moderate atopic dermatitis by the IGA and a minimum target area (right or left) situated on the forearm including the antecubital fossa with a corresponding baseline total lesional sign score (TLSS)
Part 3 Cohort A, AA and AB (patients with Netherton Syndrome):
• Patients with Netherton syndrome, male and female subjects, 18 to 65 years of age inclusive and having passed screening examinations
• Confirmed diagnosis of Netherton syndrome (SPINK5 mutation or LEKTI deficiency in the skin).
• Minimum total lesional sign score NS (TLSS-NS) of 5-9 for two selected target areas at baseline. The TLSS-NS values need to be similar between the two areas at baseline.
Other protocol-defined inclusion/exclusion criteria may apply. Refer to protocol for details. |
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E.4 | Principal exclusion criteria |
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. Other protocol-defined exclusion criteria apply in addition to those listed hereafter:
Part 1 (healthy volunteers):
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
• Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.
Part 2 (patients with atopic dermatitis):
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
• History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
• Use of topical prescription treatment for eczema within 1 week prior to initial dosing of topical corticosteroids (TCS).
• Recent previous treatment with systemic treatment including phototherapy. A washout period will be required for such patients to be eligible to participate in the trial.
Part 3 Cohorts A, AA & AB (patients with Netherton Syndrome):
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or history of serious allergic reaction.
• History of abnormal skin reactivity to UV light. Unusual exposure to UV light in the previous 3 weeks to study start (screening), including tanning and sun beds.
• Pregnant or nursing (lactating) women.
• Women of child-bearing potential must use highly effective contraception (as further defined in study protocol)
• Use of topical prescription treatment within 2 week prior to initial dosing of study drug.
• Recent previous treatment with systemic treatment. A washout period will be required for such patients to be eligible to participate in the trial.
Other protocol-defined inclusion/exclusion criteria may apply. Refer to protocol for details. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Maximum skin tolerability score
Part 2, Total Lesional Signs Score
Part 3, Clinical response using NS (TLSS-NS) score
Part 3 Cohort AA & AB, assess the potential of BPR277 (1% ointment, applied either b.i.d. or q.d.) to improve the clinical severity of lesional skin (TLSS-NS) in NS patients.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Maximum skin tolerability score:
Part 1: Day(D)1, D2-D14, and D22
Part 2: D-7, D-4, D-2, D1, D8, D15, D22, D29 & D43
Part 3: D-7, D1, D8, D15, D22, D29 & D43
Part 2, Total Lesional Signs Score: D-7, D-4, D-2, D1, D8, D15, D22, D29 and D43
Part 3, Clinical response using NS (TLSS-NS) score:
Part 3 Cohort A, D-7, D1, D8, D15, D22, D29 and D43
Part 3 Cohort AA & AB, D-7, D1, D8, D15, D29, D43 |
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E.5.2 | Secondary end point(s) |
Efficacy/Pharmacodynamics:
Part 2
Scores for each of the six clinical signs comprising the total lesional sign score; Lesional itch VAS; Investigator Global Assessment and Patient’s Global Severity Assessment
Part 3
Total lesional sign score for NS; Scores for each of the four clinical signs comprising the total lesional sign score for NS; Lesional itch VAS; Investigator Global Assessment and Patient’s Global Severity Assessment
Safety (All parts):
Vital signs, AEs, concomitant medications/significant non-drug therapies; ECG evaluations and standard clinical laboratory evaluations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy/Pharmacodynamics:
Part 2 - completed
Part 3 Cohort A - Completed
Part 3 Cohort AA & AB
Total Lesional Sign Score for NS; D-7, D1, D8, D15, D29, D43.
Lesional itch VAS & Investigator Global Assessment; D-7, D1, D8, D15, D29, D43.
Patient's global severity assessment; D-7, D1, D8, D15, D29, D43.
Vital signs (VS); D-7, D1, D15, D29, D43.
AEs,Concomitant medications/significant non-drug therapies; D-7 [except concomitant medications], D1, D8, D15, D29, D43.
ECGs; D-7, D1, D29, D43.
Standard laboratory evaluations: D-7, D1, D15, D29, D43.
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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 | No |
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Part 1 and Part 3 is intra-individual and Part 2 is parallel group comparison. |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
France |
Germany |
Netherlands |
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
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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 | 11 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 15 |