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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the achievement of partial remission by apremilast combined with doxycycline at week sixteen (t=16).
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Evaluatie van het bereiken van gedeeltelijke remissie door apremilast gecombineerd met doxycycline in week zestien (t = 16). |
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E.2.2 | Secondary objectives of the trial |
• Complete remission at week sixteen;
• Disease control at week six (t=6);
• Drug survival;
• Clinical efficacy;
• Mean decrease in periphery blood eosinophil count;
• Mean decrease in BP180 Nc16a titers by ELISA;
• Change in cytokine levels in blood and skin measured at baseline and week sixteen (t=0 and t=16);
• Change in genexpression by RNA sequencing measured at t=0 and t=16. |
• Volledige remissie in week 16;
• Disease control in week zes (t = 6);
• Verdraagzaamheid van het geneesmiddel;
• Klinische werkzaamheid;
• Gemiddelde afname van het aantal eosinofielen in het perifere bloed;
• Gemiddelde afname van BP180 Nc16a-titers met ELISA;
• Verandering in cytokineniveaus in bloed en huid gemeten bij baseline en week zestien (t = 0 en t = 16);
• Verandering in genexpressie door RNA-sequencing gemeten op t = 0 en t = 16. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult (≥ 18 years of age) male or female patients with recently diagnosed mild to moderate localized or generalized cutaneous pemphigoid, or patients that were in complete remission without treatment that have a mild to moderate flare-up of the disease. |
Volwassen (≥ 18 jaar) mannelijke of vrouwelijke patiënten met recent gediagnosticeerde mild tot matig lokaal of gegeneraliseerd cutaan pemfigoïd, of patiënten die in volledige remissie waren zonder behandeling met een milde tot matige opflakkering van de ziekte. |
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E.4 | Principal exclusion criteria |
Women of childbearing potential without contraception; women who are pregnant or planning to become pregnant or who are lactating; patients that use systemic immunosuppressive medication; any condition which would make the patient unsuitable for treatment, or requires steroid use.
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Vrouwen in de vruchtbare leeftijd zonder anticonceptie; vrouwen die zwanger zijn of van plan zijn zwanger te worden of die borstvoeding geven; patiënten die systemische immunosuppressieve medicatie gebruiken; elke aandoening die de patiënt ongeschikt zou maken voor behandeling, of steroïde gebruik vereist. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Partial remission will be analysed in week sixteen (t=16). Partial remission is defined as presence of transient new lesions that heal within one week. At week six (t= 6), patients that showed no disease control on apremilast combined with doxycycline will be excluded from the pilot study. Disease control is defined as ‘the time that new lesions cease to form and established lesions begin to heal OR pruritic symptoms start to abate (minimal 3-point decrease of VAS)”. |
Gedeeltelijke remissie zal in week zestien (t = 16) worden geanalyseerd. Gedeeltelijke remissie wordt gedefinieerd als de aanwezigheid van voorbijgaande nieuwe laesies die binnen een week genezen. In week zes (t = 6) worden patiënten die geen disease vertonen op apremilast in combinatie met doxycycline ge-excludeerd van de pilotstudie. Disease control wordt gedefinieerd als 'de tijd dat nieuwe laesies ophouden te bestaan en vastgestelde laesies beginnen te genezen OF jeuk begint te verminderen (minimale daling van VAS met 3 punten)'. |
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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) |
• Achievement of complete remission at week sixteen. Complete remission is defined as absence of new or established lesions or pruritus.30
• Proportion of patient with drug survival at t=16.
• Proportion of patients with disease control at t=6.
• Mean decrease in periphery blood eosinophil count.
• Mean decrease in BP180 Nc16a titers by ELISA.
• Change in cytokine levels in blood and skin measured at baseline and week sixteen (t=0 and t=16).
• Change in genexpression by RNA sequencing measured at t=0 and t=16.
The following outcomes will be used for measuring clinical efficacy:
• mean reduction in Visual Analogue Scale (VAS)
• mean decrease in Dermatology Quality of Life index (DLQI) and autoimmune blistering disease quality of life (AIBDQOL);
• mean reduction of Bullous Pemphigoid Disease Area Index (BPDAI). |
• Bereiken van volledige remissie in week 16. Volledige remissie wordt gedefinieerd als de afwezigheid van nieuwe of vastgestelde laesies of pruritus.
• Percentage van patiënt met disease control op t =16.
• Percentage patiënten met disease control op t=6.
• Gemiddelde afname van het aantal eosinofielen in het perifere bloed.
• Gemiddelde afname van BP180 Nc16a-titers door ELISA.
• Verandering in cytokineniveaus in bloed en huid gemeten bij baseline en week zestien (t = 0 en t = 16).
• Verandering in genexpressie door RNA-sequencing gemeten op t = 0 en t = 16.
De volgende uitkomsten zullen worden gebruikt voor het meten van de klinische werkzaamheid:
• gemiddelde reductie in Visual Analogue Scale (VAS)
• gemiddelde afname in Dermatology Quality of Life index (DLQI) en autoimmune blistering disease quality of life (AIBDQOL);
• gemiddelde afname van de Bullous Pemphigoid Disease Area Index (BPDAI). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 3, 6, 9 en 16 |
Week 3, 6, 9 en 16 |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
een arm open studie |
single arm open series |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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 | No |
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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LVLS
The criteria for terminating the study prematurely:
• Safety concerns based on reported data.
• Inaccurate or incomplete data collection.
• Falsification of records.
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LVLS
De criteria om het onderzoek voortijdig te beëindigen:
• Veiligheidszorgen op basis van gerapporteerde gegevens.
• Onnauwkeurige of onvolledige gegevensverzameling.
• Vervalsing van records. |
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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 | |
E.8.9.1 | In the Member State concerned days | |