Rituximab in Graves' disease (RIGD)

Phase 2

Completed

• Conditions: Specialty: Children, Primary sub-specialty: Diabetes and endocrinology; UKCRC code/ Disease: Metabolic and Endocrine/ Disorders of thyroid gland; Nutritional, Metabolic, Endocrine; Graves’ hyperthyroidism

• Registration Number: ISRCTN20381716
• Lead Sponsor: ewcastle Upon Tyne Hospitals NHS Foundation Trust

Brief Summary

2019 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/30670519 protocol (added 12/02/2020) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/34687316/ (added 03/03/2022)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-11-03
• Study Completion: 2021-02-28
• Last Update Posted: 14 March 2022

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

1. Excess thyroid hormone concentrations at diagnosis: elevated free tri-iodothyronine (FT3) and / or free thyroxine (based on local assay)
2. Suppressed (un-recordable) TSH (based on local assay)
3. Patients between the ages of 12-20 years inclusive who are less than 6 weeks from the initiation of anti-thyroid drug treatment (carbimazole or propylthiouracil) for the first time
4. Elevated thyroid binding inhibitory immunoglobulin or thyroid receptor antibodies (TRAb including TBII) based on local assay. Patients may or may not have a raised TPO antibody titre
5. All patients must be willing to use effective forms of contraception for 12 months post-treatment with Rituximab
6. If females are of childbearing potential, they must have a negative pregnancy test at screening. This will need to be repeated on the day of RTX administration if more than 7 days has elapsed since the screening visit or a negative pregnancy test.
7. Able and willing to adhere to a 2 year study period

Exclusion Criteria

1. Previous episodes of autoimmune thyroid disease
2. Patients with an active, severe infection (e.g. tuberculosis, sepsis and opportunistic infections) or severely immunocompromised patients
3. Patients with known allergy or contraindication to carbimazole and propylthiouracil
4. Participants with previous use of immunosuppressive or cytotoxic drugs (including Rituximab and methylprednisolone but excluding inhaled glucocorticoid and oral glucocorticoid for asthma or topical glucocorticoid for eczema)
5. Chromosomal disorders known to be associated with an increased risk of autoimmune thyroid disease including Downs’ syndrome and Turners’ syndrome
6. Pregnancy, planned pregnancy during the study period or current breast-feeding
7. Absence of informed consent from parent/legal guardian for participants age < 16 years
8. Participants with previous use of immunosuppressive or cytotoxic drugs (including Rituximab and methylprednisolone but excluding inhaled glucocorticoid and oral glucocorticoid for asthma or topical glucocorticoid for eczema)
9. Participants with significant chronic cardiac, respiratory or renal disorder or non-autoimmune liver disease. • Participants with known allergy or contraindication to Rituximab or methylprednisolone
10. 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) status
11. Participants in families who know they will be moving out of the catchment areas during the 2 years following RTX treatment
12. Participants currently involved in any other clinical trial of an IMP or who have taken an IMP within 30 days prior to trial entry

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Remission as assessed through measuring serum FT3 levels and serum thyroid stimulating hormone (TSH) concentrations in blood samples or the need for alternative treatment at 2 years.