A trial to see if anti-IgE (an antibody) will improve severe eczema that has not been cured by other types of medicine

Conditions

Severe eczema in children MedDRA version: 19.0 Level: LLT Classification code 10003641 Term: Atopic eczema System Organ Class: 100000004858 MedDRA version: 19.0 Level: LLT Classification code 10014189 Term: Eczema allergic atopic System Organ Class: 100000004858

Susan Chan, Suzie Cro, Victoria Cornelius, Rahi Jahan, Suzana Radulović et al. (6 authors)

Efficacy and Mechanism Evaluation2022-05-016 citations

10.3310/wcxn5739

Interventions

Trade Name: Xolair Product Name: Omalizumab (Xolair) Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: Omalizumab

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: The inclusion criteria for run-in are: 1. Children between the ages of 4-19 years at the time of enrolment 2. Severe eczema with i.an objective SCORAD (a validated eczema severity score) of over 40 ii.in a patient unresponsive to optimal topical therapy (potent topical steroids and topical calcineurin inhibitors) or systemic therapy. iii.in whom there is no impression of lack of compliance iv.with a (C)DLQI score of =10 v.and in whom active skin infection has been ruled out and/or adequately treated 3. Raised SpIgE (>0.35 IU/ml)or SPT (>3mm)to at least 1 food allergen or 1 aeroallergen AND/OR 4. Clinical impression that allergic exposures cause worsening eczema. 5. Total IgE level >300 kU/l. 6. Clinically proven IgE-mediated allergic disease including at least 1 of the following: i) immediate hypersensitivity to a food as proven by raised specific IgE (SpIgE) or skin prick test (SPT) greater than the 95% positive predictive value or =8mm, or a positive double blind placebo controlled food challenge, ii) allergic rhinoconjunctivitis as defined by sensitisation to a respiratory allergen and clinical history of rhinoconjunctivitis symptoms when exposed to the relevant allergen iii) allergic asthma: a history of cough, wheeze, or shortness of breath that (1) was responsive to therapy with bronchodilators on two or more occasions in the previous 24 months, (2) required one visit to a physician in the previous 24 months, and (3) occurred during the night, during early morning, or upon exercising in the intervals between exacerbations at any time in the previous 12 months and (4) where allergic exacerbations can be clinically related to an allergen exposure WITH a corresponding positive SPT or SpIgE to allergen. 7. Written informed consent to participate. Are the trial subjects under 18? yes Number of subjects for this age range: 62 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Children and/or families who are unable to comply with the regime of 2-4 weekly injections and clinic visits 2. Evidence of underlying immune compromise, autioimmune disease, immune complex mediated conditions. 3. Malignancy or a history of malignancy. 4. Known cardiovascular or ischaemic cerebrovascular abnormality. 5 Other serious or uncontrolled systemic disease. 6. Pregnancy or lactation. 7. Known history of hypersensitivity or anaphylaxis to anti-IgE injections or its constituents. 8. Insufficient understanding of the trial assessments. 9. Participation in a CTIMP in the previous 60 days or (if known) 4 halflives of the relevant medication, whichever is the greater. In this case, entry may be delayed until the appropriate time. 10. Investigator feels that there is a good clinical reason why the child would be unsuitable to participate in the study.

Design outcomes

Primary

Measure	Time frame
Main Objective: Our hypothesis is that anti-IgE is associated with an improvement in eczema severity, compared to placebo.;Primary end point(s): SCORAD (objective eczema severity score) at the end of 24 weeks of treatment with anti-IgE or placebo. ;Timepoint(s) of evaluation of this end point: 24 weeks; Secondary Objective: Primary outcome measure 1.Eczema severity:assessed by validated eczema score,objective SCORAD after 24 weeks treatment. Secondary outcome 1.Treatment failure: patients who after 12 weeks treatment have persistent severe eczema despite 2 courses of rescue therapy 2.Alternative systemic therapy: patients in whom a)alternative systemic therapy has started as a result of treatment failure(defined above) OR b)alternative systemic therapy is started after 12 weeks and by 30 weeks. 3.Eczema quality of life by questionnaire 4.Eczema severity: objective & subjective SCORAD & EASI assessments, measurements of TEWL & medical photography 5.Effect on co-existing allergic disease by questionnaire(PADQLQ) 6.Adverse events 7.Number of eczema exacerbations 8.Infective episodes of eczema 9 a)Change in free total IgE and allergen specific IgE b)the change in reactivity to food and aeroallergens 10. Change in use of potent topical steriods &calcineurin inhibitors 11.Mechanism action of anti-IgE	—

Measure

Time frame

Main Objective: Our hypothesis is that anti-IgE is associated with an improvement in eczema severity, compared to placebo.;Primary end point(s): SCORAD (objective eczema severity score) at the end of 24 weeks of treatment with anti-IgE or placebo. ;Timepoint(s) of evaluation of this end point: 24 weeks; Secondary Objective: Primary outcome measure 1.Eczema severity:assessed by validated eczema score,objective SCORAD after 24 weeks treatment. Secondary outcome 1.Treatment failure: patients who after 12 weeks treatment have persistent severe eczema despite 2 courses of rescue therapy 2.Alternative systemic therapy: patients in whom a)alternative systemic therapy has started as a result of treatment failure(defined above) OR b)alternative systemic therapy is started after 12 weeks and by 30 weeks. 3.Eczema quality of life by questionnaire 4.Eczema severity: objective & subjective SCORAD & EASI assessments, measurements of TEWL & medical photography 5.Effect on co-existing allergic disease by questionnaire(PADQLQ) 6.Adverse events 7.Number of eczema exacerbations 8.Infective episodes of eczema 9 a)Change in free total IgE and allergen specific IgE b)the change in reactivity to food and aeroallergens 10. Change in use of potent topical steriods &calcineurin inhibitors 11.Mechanism action of anti-IgE

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Secondary

Measure	Time frame
Secondary end point(s): 1. Treatment failure: patients who, after the 1st 12 weeks of treatment, have persistent severe eczema despite 2 courses of rescue therapy (0.5 to 1mg/kg/day of oral prednisolone for a week at a maximum dose of 40mg/day, followed by a week at 50% of this dose) 2. Alternative systemic therapy: in patients whom: a) alternative systemic therapy has been started as a result of treatment failure as defined above, or b) where alternative systemic therapy is started after 12 weeks and by 30 weeks. 3. Eczema quality of life: by questionnaire: POEM, (C)DLQI 4. Eczema severity by objective and subjective SCORAD and EASI (Eczema Area and Severity Index) assessments, measurements of transepidermal water loss (TEWL) and medical photography. 5. Effect on co-existing allergic disease by questionnaire (PADQLQ) 6. Adverse events: by history and investigations 7. Number of eczema exacerbations 8. Infective episodes of eczema 9 a) Change in free total IgE and allergen specific IgE b) the change in reactivity to food and aeroallergens: by skin prick tests. 10. Change in use of potent topical steroids and calcineurin inhibitors: the weight, extent and frequency of use will be recorded at each visit. 11. Mechanism of action of anti-IgE (this study will enable us to store the samples required to study the immunohistochemical changes and the immunomodulatory effects on allergenspecific T cells and FAP. There will also be an option to store blood for genetic studies.) ; Timepoint(s) of evaluation of this end point: 1. All visits 2. All visits 3. 0, 4, 8, 12, 16, 20, 24, 28, 36 and 48 weeks 4. SCORAD and EA	—

Measure

Time frame

Secondary end point(s): 1. Treatment failure: patients who, after the 1st 12 weeks of treatment, have persistent severe eczema despite 2 courses of rescue therapy (0.5 to 1mg/kg/day of oral prednisolone for a week at a maximum dose of 40mg/day, followed by a week at 50% of this dose) 2. Alternative systemic therapy: in patients whom: a) alternative systemic therapy has been started as a result of treatment failure as defined above, or b) where alternative systemic therapy is started after 12 weeks and by 30 weeks. 3. Eczema quality of life: by questionnaire: POEM, (C)DLQI 4. Eczema severity by objective and subjective SCORAD and EASI (Eczema Area and Severity Index) assessments, measurements of transepidermal water loss (TEWL) and medical photography. 5. Effect on co-existing allergic disease by questionnaire (PADQLQ) 6. Adverse events: by history and investigations 7. Number of eczema exacerbations 8. Infective episodes of eczema 9 a) Change in free total IgE and allergen specific IgE b) the change in reactivity to food and aeroallergens: by skin prick tests. 10. Change in use of potent topical steroids and calcineurin inhibitors: the weight, extent and frequency of use will be recorded at each visit. 11. Mechanism of action of anti-IgE (this study will enable us to store the samples required to study the immunohistochemical changes and the immunomodulatory effects on allergenspecific T cells and FAP. There will also be an option to store blood for genetic studies.) ; Timepoint(s) of evaluation of this end point: 1. All visits 2. All visits 3. 0, 4, 8, 12, 16, 20, 24, 28, 36 and 48 weeks 4. SCORAD and EA

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Countries

United Kingdom

Contacts

Public ContactSusan Chan

Guy`s & St Thomas` NHS Foundation Trust

susan.chan@kcl.ac.uk+4402071889730

Outcome results

None listed