E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cutaneous leukocytoclastic vasculitis is an inflammatory vascular disease and is manifested clinically by a spectrum of cutaneous lesions, although “papable purpura” is its clinical hallmark. The pathogenetic role of the deposition of immune complexes and complement in the vessel wall and the subsequent recruitment of polymorphonuclear leukocytes that mediate tissue injury have been shown. Dapsone (4,4´- diaminodiphenylsulfone, DDS) may inhibit this pathogenetic mechanism |
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MedDRA Classification |
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 |
Primary Objective To determine the efficacy of a one-month administered therapy with dapsone (1,5mg/kg) compared to placebo in subjects with cutaneous leucocytoclastic vasculitis
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E.2.2 | Secondary objectives of the trial |
·To determine the efficacy of a two-month administered maintenance therapy with dapsone (1,5mg/kg) compared to placebo in subjects with cutaneous leucocytoclastic vasculitis ·To assess the rate of complete response at weeks 4 and 12 ·To assess the durability of response after maintenance therapy at weeks 16, 24 and 36 ·To assess the rate of IgA-mediated vasculitis ·To determine the efficacy of dapsone in the different subtypes of chronic cutaneous leukocytoclastic vasculitis · To assess the safety of dapsone therapy · To assess the effects of dapsone on quality of life
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion Criteria
To be eligible for the study, subjects must meet all of the following criteria:
·Must be 18 years or older at time of enrolment; may be female or male ·Have had a diagnosis of cutaneous leukocytoclastic vasculitis (CLV) at least one month prior to screening ·Positive histologic and/or direct immunofluorescence findings ·Are candidates for systemic therapy of CLV (previous medication must be discontinued 2 weeks prior to baseline visit). ·Women of childbearing potential have to undergo a urine pregnancy test continously and must be using adequate birth control measures (eg. abstinence, oral contraceptives, intrauterine device) during dapsone therapy. ·Must be able to adhere to the study visit schedule and other protocol requirements ·Must be capable of giving informed consent and the consent must be obtained prior to any study related procedures ·Must have screening laboratory test results within the following parameters:
o Hemoglobin > 10 g/dl o Met-Hb < 5% prior to dapsone therapy o Leucocytes > 6 G/l o Serum Creatinine < 1,5 mg/dl o GOT < 50 U/l o GPT < 65 U/l o Total Bilirubin < 1.5 mg/dl o Thrombocytes > 144 G/l
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E.4 | Principal exclusion criteria |
Exclusion Criteria
·Subjects who meet any of following criteria may not be enrolled in the study: ·CLV with significant systemic manifestation and/or severe necrotizing and ulzerating cutaneous vasculitis. ·Patients with CLV of less than one month´s duration ·Have a history of any clinically significant hypersensitivity reaction/adverse reation to sulfonamides ·Patients with glucose-6-phosphate dehydrogenase, glutathione reductase or methemoglobin reductase deficieny ·Have current signs or symptoms of severe progressive, or uncontrolled renal (Creatinine Clearance<25ml/min, proteinuria, hematuria), hepatic, haematological, gastrointestinal, pulmonary, cardiac, neurologic, cerebral or psychiatric disease ·Thyroid dysfunction ( hypothyroidism ) ·Pregnancy and lactation period ·Are participating in another trial using an investigational agent or procedure during participation in this trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is the proportion of subjects who are marked responders to week 4. (Proportion of subjects achieving a >75% improvement in CLV from baseline at week 4, measured primarily by the number of cutaneous lesions per traget lesion; "target lesion" means an area of 9 cm2, being defined at screening period and showing most cutaneous involvment [number of purpura patches and papules will be ssessed]).
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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 | Information not present in EudraCT |
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) | No |
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 | No |
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.8.3 |
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 | 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 | Information not present in EudraCT |
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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After 4 weeks the data will be analysed by an independent statistican. The study will be terminated if the proportion of marked responder is below 25%.
If study treatment is discontinued due to lack of efficacy after 4 weeks, the subject should return for all scheduled evaluations. (see 4.3; study protocol)
Generally, the trial is finalised, if all included subjects (62) underwent the scheduled visits as described in the protocol. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |