Protocol change: • Baseline systemic steroids omitted. • Addition of treatment failure and alternative systemic therapies as secondary outcome measures as it was thought important to address whether treatment/placebo was associated with more failure of treatment • EASI eczema scoring added as this is increasingly used in studies • Samples to be stored for genetics studies (subject to consent). Also administrative changes to the protocol.

Changes to the secondary outcome measures and Secondary efficacy parameters. The age group between treatment group changed, Participants will be allocated to treatment group using minimisation. This is to ensure that there will be minimal imbalance of total IgE (≤1500, >1500) and age (<10 or ≥10 years) between treatment groups. In addition, there are various other administrative changes throughout the whole protocol and the labels

The inclusion of the Transepidermal Water Loss test (TEWL), an additional optional test at Baseline, Week 24, 36 and 48.The exclusion criteria has been amended with pre-existing hepatic or renal impairment being removed, and the definition of ‘Exacerbations of eczema’ in section 6.2 of the protocol has been clarified. Additionally, the timepoint for urine testing has been changed from baseline to screening and the protocol has been revised to clarify the Xolair dosing for IgE levels at the limits of the dosing table. In addition, skin swabs will now not be taken from family members or at the end of treatment for any infections. There have been various other administrative changes and clarifications throughout the protocol and section 8.3 has been updated to bring it in line with the statistical analysis plan.

Inclusion of a new secondary outcome measure as listed below and the statistics section has also been updated in line with the new version of the Statistical analysis plan. Below is a list of all changes made to the protocol: 1. Trial Flowchart TEWL timing updated from screening to baseline visit, in line with the rest of the protocol. 2. Clarification of primary outcome measures 3. Inclusion of a new secondary outcome measure - ‘Change in use of potent topical steroids and calcineurin inhibitors: the weight, extent and frequency of use will be recorded at each visit.’ 4. Clarification of inclusion criteria 5. Clarification on treatment of eczema exacerbations to include that treatment can follow that ‘as decided by the supervising physician’ as well as the regimen included in the protocol. 6. Statistics section updated in line with latest version of the Statistical Analysis Plan (SAP, version 2.0) 7. Addition of protocol version history 8. Staff update on the ADAPTrial study website and administrative corrections to the parent and child consent forms.