A randomised controlled trial of adjuvant rituximab in young people with Graves’ disease (RigD2)

Research summary

This randomised phase III trial will determine whether adjuvant RTX increases remission rate when compared to standard ATD treatment in young people with GD. The primary endpoint will be a comparison of the proportion of subjects in remission at 3 years (subjects not requiring ATD for 12 months) following a 2-year course of ATD +/- RTX in the two treatment arms. Secondary outcomes include an analysis of lymphocyte subsets,cytokines,chemokines and immunological and genetic markers of B lymphocyte activity compared to outcome as well as quality of life. A UK,multi-centre randomised,placebo controlled,single-blinded (to participants) trial will investigate the efficacy of adjuvant RTX compared to standard ATD treatment. Newly diagnosed GD patients (12 to 24 years) will be recruited and randomised 1:1 to ATD or ATD + RTX. Treatment allocation will be performed by stratification for sex,age at diagnosis and initial free T4 level. Assuming 90% power to detect a 24% difference in remission rate (24% remission with ATD alone to 48% from proof-of-concept study) 124 participants will be recruited to take into consideration a 10% drop out figure. We will use regional networks and work with the British Thyroid Foundation and British Society for Endocrinology and Diabetes to ensure that the 26 tertiary centres within the UK (13 paediatric and 13 adult sites) recruit to target. We will carry out a clinical trial throughout the UK,where 124 young people with GD,aged 12-24 years,will be randomly allocated to one of two different groups: 1) 2 year course of ATD 2) 1 dose of RTX soon after presentation and 2 years of ATD Participants will not know whether they receive RTX via a drip or a salt water infusion instead. They will have bloods taken to check thyroid function at 4 weeks and then every 8 weeks in the first year and 3- monthly thereafter. The visit frequency is similar to standard care. Travel costs will be reimbursed. The primary outcome will be a comparison of numbers in each group with normal thyroid function and who have had no further treatment 12 months after stopping ATD. If RTX improves remission rates,it could be introduced as a new component of standard treatment.

Principal Investigator

Dr Lia Anguelova

Contact us

Email: diabetes.research1@ouh.nhs.uk

IRAS number

1010765