E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic spontaneous urticaria |
chronische spontane urticaria |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
To relate the reduction of inflammatory characteristics in the skin and peripheral blood to clinical efficacy of Xolair (omalizumab) in patients with CSU. |
Het relateren van de reductie in inflammatoire kenmerken in huid en perifeer bloed, aan de klinische effectiviteit van omalizumab in patiënten met CSU. |
|
E.2.2 | Secondary objectives of the trial |
To determine the clinical efficacy of Xolair (omalizumab), measured by disease activity, disease control and quality of life |
Het bepalen van de klinische effectiviteit van omalizumab, gemeten met ziekteactiviteit, ziektecontrole en kwaliteit van leven. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age ≥ 18 years
Diagnosis of CSU according to recent international guidelines
Moderate or severe disease activity (UAS7 ≥ 16) despite current treatment with H1 antihistamines according to recent international guidelines
Sufficient washout of treatment with immunosuppressants (several washout periods are pre-defined). |
Minimale leeftijd van 18 jaar
Diagnose CSU volgens recente Europese richtlijn
Gemiddelde of ernstige ziekteactiviteit (UAS7 ≥ 16) ondanks behandeling met H1 antihistaminica volgens recente Europese richtlijn
Behandeling met immunosuppressieve medicatie is voldoende lang gestaakt voorafgaand aan het onderzoek (er zijn verschillende periodes hiervoor gedefinieerd) |
|
E.4 | Principal exclusion criteria |
Other urticarias than CSU, including but not limited to CINDU
Hypersensitivity to omalizumab or any component of the formulation |
Andere vormen van urticaria, waaronder CINDU
Overgevoeligheid voor omalizumab of een van de hulpstoffen. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the reduction of inflammatory characteristics in the skin in responders and non-responders of treatment with Xolair (omalizumab), thereby exploring the reduction in inflammatory parameters by analysis of complement deposition and infiltration of FcεRI-bearing leukocytes such as basophils.
Changes in inflammatory parameters in the skin will also be related to changes in levels of circulating complement components and the reduction of the in vitro activation state and numbers of basophils. |
Het primaire eindpunt is de vermindering van inflammatoire karakteristieken in de huid in patiënten met en zonder respons op omalizumab. Daartoe wordt de vermindering in complement depositie en infiltratie van FcεRI-houdende leukocyten zoals basofielen geanalyseerd.
Veranderingen in inflammatoire karakteristieken in de huid worden daarnaast gerelateerd aan veranderingen in het bloed, namelijk circulerende complement cascade componenten, en de activatiestaat en aantallen basofiele granulocyten. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Skin biopsies will be performed at baseline, after 24 hours and after 2 weeks.
Venipunctures will be performed at baseline, 1,2, 6 and 24 hours after the first dose of omalizumab, 1 and 2 weeks after the first dose of omalizumab, before and 2 hours after the second dose of omalizumab and subsequently every 4 weeks, before the next dose of omalizumab. Three months after the last (6th) dose, a last venipuncture will be performed. |
Huidbiopten worden afgenomen voor aanvang van de behandeling en 24 uur en 2 weken na de eerste gift.
Daarnaast zullen venapuncties plaatsvinden voor aanvang van de behandeling, 1,2, 6 en 24 uur en 1 en 2 weken na de eerste gift omalizumab, voor en 2 uur na de tweede gift omalizumab en voorafgaand aan iedere volgende gift omalizumab. Drie maanden na de laatste (6e) gift omalizumab wordt een laatste venapunctie verricht. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoint is the clinical efficacy of omalizumab. Disease severity (UAS7, AAS), Quality of life (CU-QoL, AE-QoL, DLQI), and disease control (UCT) will be measured for this purpose. |
Het secundaire eindpunt is de effectiviteit van omalizumab, gemeten met ziekteactiviteit (UAS, AAS), ziekte controle (UCT) en kwaliteit van leven (CU-QoL, AE-QoL, DLQI). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
UAS7 and when applicable AAS will be used throughout the study. At baseline, after three months of treatment and at the last follow up visit, CU-QoL, DLQI and if applicable AE-QoL will be used. UCT will be used every visit where patients receive a dose of omalizumab, and at the last follow-up visit. |
UAS7 en, wanneer van toepassing AAS, zullen gedurende de hele studie worden gemeten. Vragenlijsten aangaande kwaliteit van leven (CU-QoL, DLQI en indien van toepassing AE-QoL) worden ingevuld bij baseline, na 3 maanden behandeling en bij het laatste follow-up bezoek. De UCT wordt ingevuld bij iedere gift omalizumab en bij het laatste follow-up bezoek. |
|
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 |
Prospectieve cohort studie |
prospective cohort study |
|
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 | 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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | |