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 |
Moderate to severe atopic dermatitis |
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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 | 17.1 |
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 assess the efficacy of OC000459 50 mg given once a day orally in comparison to placebo on the severity and extent of atopic dermatitis using the Eczema Area and Severity Index (EASI) after a 16 week treatment period by subjects with active moderate to severe atopic dermatitis (AD) requiring treatment. |
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E.2.2 | Secondary objectives of the trial |
• To assess the effects of OC000459 in comparison with placebo on various aspects of atopic dermatitis flare – number of flares, time to first flare, time to resolution of flares, proportion of flare free days (days where topical corticosteroids are not used)
• To assess the effects of OC000459 in comparison with placebo on the use of rescue medication as an indication of control of atopic dermatitis
• To assess the effects of OC000459 in comparison to placebo on subject withdrawal from the study due to treatment failure
• To assess whether the presence or absence of Chemoattractant Receptor-Homologous molecule expressed on Th2 cells (CRTH2) related single-nucleotide polymorphism (SNP) affects the efficacy of OC000459 in the treatment of subjects with moderate to severe atopic dermatitis compared to placebo
For the full list of Study Secondary Objectives please refer to Study Protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Atopic dermatitis as defined by a score of at least 9 on the Nottingham Eczema Severity Score, stratified into moderate (score 9 to 11 inclusive) and severe (score 12 to 15 inclusive) disease.
2. Well documented history of AD over the past 2 years in the patient notes, including the use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) and any investigator severity scores (EASI/SCORAD). Subjects without a well-documented history will be excluded from the study.
3. Male and female subjects with moderate to severe atopic dermatitis treated with TCS and/or TCI ONLY (with or without emollients) at the time of screening and over the previous month.
4. Subjects must have had at least one flare in the previous 6 months.
5. Any racial group.
6. Females of childbearing potential (i.e. having had a menstrual period within two years prior to the date of screening) must practise two forms of contraception (i.e. two of the following – oral contraception, barrier contraception, spermicide, intrauterine device) during the study and for three months thereafter and must have a negative pregnancy test (blood or urine) at screening.
Men whose partners could be of child bearing potential should routinely use a condom during the study and for three months thereafter. The partner, if not pregnant, should also use a reliable form of contraception such as the oral contraceptive pill or an intrauterine device.
7. Aged 18 to 48 years inclusive, stratified into subjects aged 18 to 30 inclusive and over 30 to 48 inclusive. The aim will be to recruit 50% of subjects into each group.
8. Documented history of atopy– subjects without a fully documented history will be excluded from the study.
9. Eosinophils > 0.25 x 109/L blood at visit 1 (screening).
10. Total Serum IgE ≥ 1000kU/L at the screening visit.
11. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
12. Available to complete the study.
13. Subjects with health insurance coverage (France only). |
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E.4 | Principal exclusion criteria |
1. Clinically significant abnormality in clinical laboratory tests at screening (visit 1) as determined by the Principal Investigator or designee.
2. Subjects with chronic conditions requiring daily medication will be excluded from the study except those subjects with asthma and/or allergic rhinitis, depression, hypertension, migraine, epilepsy and thyroid conditions.
3. Subjects testing positive for hepatitis C antibody, hepatitis B surface antigen or HIV.
4. Receipt of any forbidden medication including over the counter preparations and herbal medicines within 14 days of the first dosing day with the exception of paracetamol up to a maximum of 2 g daily, anti-depressants, anti-hypertensives, anti-migraine, anti-epileptics, oral contraceptives, hormone replacement therapies and thyroid medications
5. Use of systemic corticosteroids 4 weeks prior to the screening visit, light therapy or immunosuppressants 4 weeks prior to the screening visit.
6. Chronic use of NSAIDs
7. Subjects with contact dermatitis will be excluded.
8. Subjects with acute skin infection or acute disease flares. Subjects with active flares during the screening to randomisation period (visits 1 to 2) may be managed according to normal clinical practice and be rescreened once their flares are no longer active.
9. Subjects with a known allergy to hydrocortisone, hydrocortisone butyrate 0.1% cream (Locoid® cream, Alfason® creme) or hydrocortisone acetate will be excluded.
10. Participation in a study of an unlicensed drug or blood donation in the 3 months prior to the study.
11. The subject regularly, or on average, drinks more than four units of alcohol per day and/or uses drugs of abuse.
12. Females of child bearing potential who are unwilling to use two forms of contraception during the study and for a week after the last exposure to study medication.
13. Females who are pregnant or breastfeeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in EASI score after 16 weeks of treatment with OC000459 compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weeks 0, 2, 4, 8, 12, 16, 18, 20. |
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E.5.2 | Secondary end point(s) |
• Number of flares, time to first flare, time to resolution of flares (when subject stops medicating) and proportion of flare free days (days where topical corticosteroids are not used) during 16 weeks of treatment with OC000459 compared to placebo according to the subjects’ daily diary completion.
• Change in the clinical manifestations (symptoms) of active Atopic Dermatitis, assessed by means of the IGA, SCORAD, itch question, PEST and PO-SCORAD during 16 weeks of treatment with OC000459 compared to placebo.
• Proportion of subjects withdrawing from the study due to treatment failure
• Levels of total serum IgE following 16 weeks treatment with OC000459 or placebo.
For other secondary end points please see the protocol. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 0, 2, 4, 8, 12, 16, 18, 20 |
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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 | No |
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 | Yes |
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) | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 | 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 | 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 | 6 |