Medical condition: Graves disease Medical condition in lay language: Graves Disease (autoimmune hyperthyroidism). Therapeutic areas: Diseases [C] - Immune System Diseases [C20] Other
Conditions
Interventions
Arm 1- Standard ATD therapy + Placebo: Participants will receive an intravenous (IV) infusion of saline (0.9% NaCl) over 3 hours together with antipyretic, antihistamine and steroid cover administered
Safety bloods (all visits)
Additional bloods (visits 1 and 10)
• Questionnaires administered (visits baseline, 2, 7, 10, 14, 18)
• AEs and SAEs checked recorded/reported
Visit 14 (end of year 2)
• Stop ATD therapy
Visits 15-
Research Bloods (visit 18 only)
• AEs and SAEs checked recorded/reported
• Questionnaires administ
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
12 Years to 24 Years
Inclusion criteria
Inclusion criteria: 1. Excess thyroid hormone concentrations at diagnosis: elevated FT3 and/or FT4 (based on local assay) 2. Suppressed (un-recordable) TSH (based on local assay) 3. Patients between the ages of 12-24 years inclusive who are less than 12 weeks from the initiation of ATD treatment (CBZ or PTU) for the first time 4. Elevated thyroid binding inhibitory immunoglobulin or thyroid receptor antibodies (TRAb including TSH-Binding Inhibitor Immunoglobulins (TBII)) based on local assay. Patients may or may not have a raised TPO antibody titre 5. Confirmation of no current pregnancy. Participant must be willing to undergo pregnancy testing, as stipulated in protocol section 3.2.4. 6. Willingness to use effective forms of contraception for 12 months post-treatment with RTX/placebo (for sexually active patients, see protocol section 3.2.5) 7. Able and willing to adhere to a 3-year trial period 8. Able to provide informed consent (parent/legal guardian can if <16 years of age or is an adult lacking capacity)
Exclusion criteria
Exclusion criteria: 1. Previous episodes of autoimmune thyroid disease 2. Patients with an active, severe infection (e.g. tuberculosis, sepsis and opportunistic infections) 3. Severely immunocompromised patients 4. Patients with known allergy or contraindication to carbimazole and propylthiouracil 5. Participants with previous use of immunosuppressive or cytotoxic drugs (including RTX and methylprednisolone but excluding inhaled glucocorticoid and oral glucocorticoid for asthma or topical glucocorticoid for eczema) 6. Chromosomal disorders known to be associated with an increased risk of autoimmune thyroid disease including Downs’ syndrome and Turners’ syndrome 7. Currently pregnant or planning to become pregnant during the trial period 8. Currently breast-feeding 9. Participants with significant chronic cardiac, respiratory or renal disorder or non-autoimmune liver disease 10. Participants with known allergy or contraindication to RTX or methylprednisolone 11. Participants with evidence of Hepatitis B/C infection, assessed by determining hepatitis ‘B’ surface antigen (HBsAg) status, hepatitis ‘B’ Core antibody (HB Core antibody) status and hepatitis ‘C’ virus antibody (HCV antibody) 12. Participants with evidence of Tuberculosis infection, assessed by Quantiferon test 13. Participants in families who know they will be moving out of the United Kingdom during the 2 years following RTX treatment and thus unable to commit to attending follow-up visits 14. Participants currently involved in any other clinical trial of an IMP or who have taken an IMP within 30 days prior to trial entry 15. Absence of informed consent from parent/legal guardian for participants age <16 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients in remission from GD measured using thyroid function tests (TSH, free T4 and free T3) and the remission rate at 2 years post-ATD treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The cumulative ATD dosage at the end of the treatment period, the time to stop ATD and the dosage of ATD measured using prescribed medication doses and patient reported compliance at the end of 24 months (V14) 2. The time to recovery (measured in days) of B cell numbers (CD 19+ cells) to 1% of total lymphocytes and concentrations of TRAb antibody levels at visits 1, 2, 7, 10, 14 and 18. Immunological markers will also be analysed by regimen, in relation to thyroid hormone status and as a predictor of relapse 3. The total number of serious adverse events measured using summative total from database from Day 0 (Baseline) to the participant's last visit (V18) 4. Quality of life (QoL) measured using the thyroid-specific QoL questionnaire (ThyPRO-39) and utility values measured using the EQ-5D-5L/EQ-5DY-5L questionnaires at visits 2, 7, 10, 14, and 18 5. Cumulative ATD dosage at the end of the treatment period, the time to stop ATD and the dosage of ATD using prescribed medication doses and patient reported compliance at the end of 24 months (V14) 6. Time to recovery (measured in days) of B cell numbers (CD 19+ cells) to 1% of total lymphocytes and concentrations of TRAb antibody levels at visits 2, 7, 10, 14, and 18 7. The total number of serious adverse events from Day 0 (Baseline) to the participant's last visit (V18) at 3 years. | — |
Countries
United Kingdom
Contacts
Public ContactClaire Wood
Outcome results
None listed