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 |
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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 evaluate the efficacy of 8 weeks treatment of 30 mg od ZPL-3893787 on pruritus in adult subjects with moderate to severe atopic dermatitis. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of 8 weeks treatment of 30 mg od ZPL-3893787 in adult subjects with moderate to severe atopic dermatitis.
To evaluate the efficacy of 8 weeks treatment of 30 mg od ZPL-3893787 on severity of AD skin lesions in adult subjects with moderate to severe atopic dermatitis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 12 months prior to screening. Chronic AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka (Eichenfield, 2004).
*Females should be either of non child-bearing potential or must agree to use highly effective methods of contraception. Males with partners who are WOCBP must also use contraception
* Eczema Area and Severity Index (EASI) of ≥12 and <48.
* An Investigator’s Global Assessment (IGA) score ≥ 3 at both Screening and Day 0.
* A mean pruritus score of ≥ 5 on a 0-10 scale over the 7 day Run In (Days -7 to -1)
* Atopic dermatitis affecting ≥10% BSA
* Patients must be willing to apply stable amounts of an additive-free, basic, bland emollient, twice daily for at least 7 days before the baseline visit.
* Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1 AD of such severity (EASI >48) that the subject could not comply with the demands of the study and/or the subject is not a suitable candidate for a placebo-controlled study
2 Have concurrent skin disease (e.g. acne) of such severity in the study area that it could interfere with the study evaluation or presence of skin comorbidities that may interfere with study assessments.
3 Have an active skin infection or any other clinically apparent infections.
4 Hypersensitivity to mometasone or to any other ingredients contained by the topical corticosteroid product used as rescue medication in the study.
5 Have received phototherapy (e.g. UVA, UVB), or systemic therapy (e.g. immunosuppressants, cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the Run In.
6 Have received systemic corticosteroids ([CS] e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the Run in. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate.
7 Were treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting Run In; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.
8Use of a tanning booth/parlour within 4 weeks before start of the Run In.
9 Have used antiseptic treatments (e.g. bleach baths, potassium permanganate etc.) within 4 weeks before the start of the Run In. (Patients who have recently used antiseptic treatment may be rescreened at a later date if they wish to participate in the study and agree to stop antiseptic treatment.)
10 Evidence of significant concomitant clinical disease that may need a change in management during the study or could interfere with the conduct or safety of this study (Stable well-controlled chronic conditions such as controlled hypertension (BP<140/90 mmHg) thyroid disease, well-controlled Type 1 or Type 2 diabetes (HbA1c< 8%), hypercholesterolemia, gastroesophageal reflux, or depression under control with medication (other than tricyclic antidepressants), are acceptable provided the symptoms and medications would not be predicted to compromise safety or interfere with the tests and interpretations of this study).
11 Clinically significant cardiac disease or ECG abnormalities, including:
Predominant heart rhythm other than normal sinus rhythm
AV block greater than first degree
Resting heart rate >100 or <50 bpm
Electrocardiographic evidence or a history of myocardial infarction
Electrocardiographic evidence of conduction system abnormality
Subjects with pre-randomization evidence of QTc prolongation (defined as >450 msec). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) over 24 hours |
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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) |
Secondary Endpoints: Efficacy
Change from baseline in the daytime NRS for Pruritus (Worst Itch)
Change from baseline in the night time NRS for Pruritus (Worst Itch)
Change from baseline in the NRS for Sleep Disturbance
Change from baseline in Duration of Itching
Change from baseline in Verbal Rating Score (VRS) for Pruritus
Change from baseline in the Eczema Area and Severity Index (EASI) score
Change from baseline in the SCORing Atopic Dermatitis (SCORAD) score
Investigators Global Assessment (IGA) Score
Amount of rescue medication use
Patient Global Impression of Change (PGIC)
Secondary Endpoints: Safety
Adverse events, vital signs, temperature, 12-lead ECG, laboratory safety tests (clinical chemistry, hematology, urinalysis). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |