E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunoglobulin A vasculitis |
vascularite à Immunoglobuline A
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E.1.1.1 | Medical condition in easily understood language |
Ig A vasculitis |
vascularite à IgA |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047121 |
E.1.2 | Term | Vasculitis Henoch-Schonlein like |
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 |
Evaluation of efficacy of colchicine versus placebo to prevent cutaneous relapses, 6 months after inclusion, in adult patients with cutaneous IgA vasculitis alone or associated with non-severe digestive or renal involvement. |
Evaluation de l'efficacité de la colchicine par rapport au placebo pour prévenir les rechutes cutanées, 6 mois (M6) après l'inclusion, chez des patients adultes présentant une vascularite à IgA cutanée isolée ou associée à une atteinte digestive ou rénale non sévère. |
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E.2.2 | Secondary objectives of the trial |
1/ To assess efficacy of colchicine vs. placebo at M6 in: - Preventing cutaneous relapses - Preventing extra-cutaneous (articular and/or digestive and/or kidney) new involvements or relapses 2/ To assess a remanent effect of colchicine vs. placebo at M12 in: - Preventing cutaneous relapses - Preventing extra-cutaneous (articular and/or digestive and/or kidney) new involvements or relapses 3/ To assess efficacy of colchicine vs. placebo in preventing relapses consequence 4/ To assess colchicine safety (adverse events) and compliance
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1/ Evaluer l’efficacité de la colchicine/placebo pour -Prévenir les rechutes cutanées -Prévenir l’apparition ou la rechute des atteintes extra-cutanées (articulaire, digestive, rénale). 2/ Evaluer l’effet rémanent de la colchicine/placebo en évaluant à 1 an (6 mois après l’arrêt du traitement) les rechutes cutanées et extra-cutanées. 3/ Evaluer l’efficacité de la colchicine/placebo pour prévenir les conséquences des rechutes cutanées en utilisant des scores de qualité de vie (SF-36 et HAQ ) et en comptabilisant les jours d’arrêt de travail en rapport avec la maladie. 4/ Evaluer la tolérance (effets secondaires) et la compliance au traitement (colchicine/placebo).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) Age ≥ 18 years and < 85 years b) IgA-V recently diagnosed (< 20 days since skin biopsy) and defined by : - Histologically proven small vessels vasculitis with IgA deposits IgA Vasculitis - Purpura and/or involvement of at least one organ among kidney, joint, or intestinal tract
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a) Age ≥18 ans et < 85 ans b) V-IgA de diagnostic récent (moins de 20 jours suivant la biopsie cutanée) et défini par : - V-IgA prouvé histologiquement (vascularite des petits vaisseaux avec dépôt d’IgA) - purpura et/ou atteinte d’au moins un organe parmi: rein, articulation, tube digestif.
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E.4 | Principal exclusion criteria |
a) Severe renal IgA vasculitis: - impaired renal function, defined as an eGFR < 60 ml per minute per 1.73 m2 (MDRD or CKD-EPI formula) - proteinuria/creatiniuria> 1g/l - Uncontrolled blood pressure (Systolic blood pressure > 170 mmHg, diastolic blood pressure > 100 mmHg) b) Severe digestive IgA vasculitis: - intussusception - massive gastrointestinal haemorrhage - intestinal ischemia - perforation - abdominal pain persisting more than one day (EVA > 5) and unresponsive to standard analgesics (level 1 or 2). c) Prior (< 3 months) immunosuppressive or corticosteroid therapy d) Additional cutaneous, and/or digestive and/or chronic renal diseases. e) HIV and B and C Chronic hepatitis f) Pregnancy or breast feeding or women without sufficient contraception among women of childbearing g) Known allergy or intolerance to study medication or any of its excipients (lactose, saccharose) h) Contraindication to colchicine such as: - severe hepatic insufficiency - combination with a macrolide (except spyramicin), - combination with pristinamycin i) Participation in another interventional trial j) Patient having not signed an informed consent k) Patient without Social Security System Insurance
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a) V-IgA avec atteinte rénale sévère : - Altération de la fonction rénale définie par un DFGe <60ml/min/1.73 m2 (MDRD ou CKD-EPI) - Ratio protéinurie/créatininurie> 1g/g l - Pression artérielle non contrôlée (PAs >170 mmHg, PAd > 100 mmHg) b) V-IgA avec atteinte digestive sévère : - Invagination - Hémorragie digestive massive - Ischémie digestive - Perforation - Douleurs abdominales persistantes plus d’une journée, évalué à plus de 5 sur échelle EVA et résistantes aux antalgiques usuels (classe 1 et 2). c) Traitement immunosuppresseur ou corticothérapie récente (<3 mois) d) Comorbidité dermatologique, digestive ou rénale e) HIV, infection chronique par hépatite B ou C. f) Grossesse, allaitement, absence de contraception chez les femmes en âge de procréer g) Allergie ou intolérance connue à la colchicine ou à ses excipients (lactose, saccharose) h) Contre-indications à la colchicine telles que : insuffisance hépatique sévère, association avec un macrolide (sauf spyramicine), association avec la pristinamycine i) Participation à une autre étude interventionnelle j) Patient n’ayant pas signé de consentement k) Patient sans sécurité sociale
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of patients who have presented at least one cutaneous relapse in the colchicine group versus the placebo group, 6 months after inclusion. Cutaneous relapse is defined by reappearance of palpable purpura with lower limb predominance and not related to thrombocytopenia. |
nombre de patients qui ont présenté au moins une rechutes cutanée à 6 mois. La rechute cutanée est définie par : Apparition de nouvelles lésions cutanées, à prédominance déclive, sans rapport avec une thrombopénie |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Number of patients who have presented at least one cutaneous relapse 6 months after inclusion |
nombre de patients qui ont présenté au moins une rechutes cutanée à 6 mois après l'inclusion. |
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E.5.2 | Secondary end point(s) |
- Time (in days) to first cutaneous relapse - Number of cutaneous relapses per patients at M6 and M12 - Rate of patients who have presented at least a severe cutaneous relapse at M0, M6 and M12 - 36-item Short-form Health Survey (SF-36) score at M6 and M12 - Rate of patients displaying at least one work stoppage related to IgAV between M0 and M12 and number of days of work stoppage per patient. - Rate of patient who consulted in emergency for IgA relapse or new organ involvement between M0 and M12. - Adverse events associated with Colchicine and compliance at M3 and M6 - Clinical, biological and histological candidate predictors at diagnosis.
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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 | Yes |
E.6.4 | Safety | No |
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 | 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 | 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 | 32 |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |