E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Discoid lupus erythematosus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013072 |
E.1.2 | Term | Discoid lupus erythematosus |
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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 purpose of the study is to determine predictors of response to hydroxychloroquine sulphate therapy for discoid lupus erythematosus (DLE).
The main objective is to determine whether polymorphisms in the cytochrome P450 (CYP) genes (CYP2C8, CYP2D6) and Ah receptor gene, which encode or interact with the enzymes thought to be responsible for hydroxychloroquine sulphate metabolism in vitro, are related to drug efficacy and/or toxicity in vivo. |
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E.2.2 | Secondary objectives of the trial |
To determine, in the context of discoid lupus erythematosus:
(a)whether epidermal levels of the cutaneous drug-metabolising enzyme CYP1A1 are correlated with response to hydroxychloroquine sulphate.
(b) whether whole blood and epidermal hydroxychloroquine sulphate (and metabolite) levels correlate with response to therapy.
(c) whether hydroxychloroquine sulphate efficacy is related to cigarette smoking and cutaneous CYP1A1 levels.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The study is describe in full in the attached protocol.
We will perform a retrospective study and a prospective study which is described in detail in the attached protocol.
For the retrospective study:
Patients will be included in the retrospective study if they have clinical and histopathological criteria of discoid lupus erythematosus and have previously taken hydroxychloroquine sulphate (for 3 months or more) as part of their standard management by their responsible dermatologist at their specialist clinic. They need not be on treatment currently.
For the prospective study:
Patients will be included in the prospective study if they have clinical and histopathological criteria of discoid lupus erythematosus and are about to be started on hydroxychloroquine sulphate as part of their standard management by their responsible dermatologist at their specialist clinic.
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E.4 | Principal exclusion criteria |
We will not be including minors.
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E.5 End points |
E.5.1 | Primary end point(s) |
For the retrospective study:
Efficacy of hydroxychloroquine sulphate therapy will be determined by reviewing the case notes of participants and assessing response from the medical entries recorded 12 weeks after starting treatment. Response will be categorised as (i) complete clearance; (ii) partial clearance; (iii) no change; (iv) worse. In accordance with the classification used in previous studies, responders will be defined as the total number in groups (i) and (ii) and non-responders as total number in groups (iii) and (iv).
We will determine the proportion of responders and non-responders to hydroxychloroquine with polymorphisms in CYP450 and Ah receptor genes. We will also determine whether levels of epidermal CYP1A1 and smoking status is associated with the documented previous response to the drug.
For the prospective study:
Response to hydroxychloroquine sulphate in discoid lupus erythematosus after 6 months of treatment at standard dose (400mg/day) will be assessed using global assessments of disease and treatment control. Disease activity and damage scores will also complement these assessments. Response will be categorised as (i) complete clearance of lesions; (ii) partial clearance of lesions; (iii) no change; (iv) worse. In accordance with the classification used in previous studies, responders will be defined as the total number in groups (i) and (ii) and non-responders as total number in groups (iii) and (iv).
We will determine the proportion of responders and non-responders to hydroxychloroquine with polymorphisms in CYP450 and Ah receptor genes and also determine whether levels of epidermal CYP1A1 and smoking status is associated with response. We will also determine whether levels of the drug and its metabolites in whole blood and in the skin are correlated with degree of response.
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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 | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 9 |
E.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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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This will be the last visit of the last patient in the prospective study. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |