Autoimmune Addison's disease (adrenocortical failure) MedDRA version: 9.1 Level: HLT Classification code 10001343 Term: Adrenal cortical hypofunctions
Conditions
Interventions
Trade Name: MabThera
Product Name: MabThera
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Solu-medrone
Product Name: Solu-medrone
Pharmaceutical Form: Powder for injection*
Sponsors
Newcastle upon Tyne Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Age 16 to 65 years -Clear evidence of adrenocortical failure (AAD) with subnormal cortisol response to IV synacthen plus either clinical or biochemical evidence to confirm elevated ACTH, or evidence of mineralcorticoid insufficiency - Patients are less than 4 weeks from first diagnosis of presumed AAD - Basal or ACTH stimulated cortisol >150nmol/l - Normal or atrophic adrenal glands on CT scan - Willingness to travel to the Wilson Horne Immunotherapy Centre, Newcastle or Harbourne Ward, Royal Devon and Exeter Hospital, for study - Willingness to attend education sessions about indications for parenteral glucocorticoid administration and technique of administration. -Female participants of child-bearing age willing to take acceptable contraception during study and for 12 months following last rituximab dose Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Active viral illness, including HIV, Hepatitis B or C, shingles/Zoster - Recent or partially treated TB; unexplained radiographic abnormality on chest X-ray - Previous use of immunosuppressive or cytotoxic drugs (excluding glucocorticoid) - Diabetes mellitus - Significant cardio-respiratory, chronic renal or non-autoimmune liver disease; malignancy - Pregnancy, breast feeding or plan for pregnancy within 24 months - Known non-autoimmune cause for adrenal failure - Other contraindications to rituximab therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary endpoint is recovery of steroidogenic capacity as judged by basal and dynamic endocrine testing;Secondary Objective: Improvement in basal ACTH or (recumbent) renin and aldosterone levels Change in 21-hydroxylase antibody titres Change in peripheral B-cell counts Serious adverse reactions; bacterial infections requiring antibiotics; other infective episode Patient-reported non-serious adverse events Patient-reported quality of life (EUROQOL-EQ5D questionnaire) ;Primary end point(s): - Restoration of normal glucocorticoid secretion (peak cortisol >550nmol/l after synacthen) | — |
Countries
United Kingdom
Outcome results
None listed