Autoimmune Addison's disease: autoimmune primary adrenal insufficiency MedDRA version: 16.1 Level: PT Classification code 10052381 Term: Primary adrenal insufficiency System Organ Class: 10014698 - Endocrine disorders MedDRA version: 16.1 Level: LLT Classification code 10001335 Term: Adrenal cortex insufficiency System Organ Class: 100
Conditions
Interventions
Trade Name: Mabthera infusion
Product Name: Mabthera Infusion
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Clear evidence of adrenocortical failure with subnormal cortisol response to 250?g IV synacthen (peak cortisol 50nmol/l - Patients are less than 8 weeks from first diagnosis of AAD - Positive serum 21-hydroxylase autoantibodies (>1.0 IU/l on RSR assay) - Normal or atrophic adrenal glands on CT scan - Willingness to travel to the relevant site for study - Willingness to attend education sessions about indications for parenteral glucocorticoid administration and technique of administration. Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 26 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - Active viral illness, including HIV, Hepatitis B or C, shingles/Zoster - Recent or partially treated TB or unexplained radiographic abnormality on chest X-ray - Previous use of immunosuppressive or cytotoxic drugs (excluding glucocorticoid) - Significant cardio-respiratory (inc. asthma), chronic renal or non-autoimmune liver disease - Pregnant or breastfeeding and with no plan for pregnancy/ breastfeeding within 24 months - Allergy to synacthen, synacthen depot, rituximab or methylprednisolone
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to restore adrenal function in patients with recent onset autoimmune Addison's disease. This study will answer the following questions: In people with new-onset autoimmune Addison’s disease will the therapeutic regimen of rituximab and ACTH allow improvement or recovery of adrenal function? ; Secondary Objective: •Will this therapeutic regimen result in amelioration of the humoral immune response by reducing autoantibody titres? •What are the adverse effects of this therapeutic regimen? •Will the regimen be acceptable and well-tolerated by patients? •What is the early natural history of conventionally treated AAD? ;Primary end point(s): Peak serum cortisol in response to IM synacthen testing at 48 weeks.;Timepoint(s) of evaluation of this end point: 48 weeks post first treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Restoration of normal glucocorticoid secretion (peak cortisol >550nmol/l after repeat synacthen testing at 6, 12, 24, and 72 weeks) - Improvement of basal and peak cortisol response (>100nmol/l over baseline) to synacthen testing - Normalisation of ACTH, DHEAS, 17a OH-progesterone and recumbent renin and aldosterone levels ;Timepoint(s) of evaluation of this end point: at 6,12,24, 48 and 72 weeks | — |
Countries
United Kingdom
Contacts
Public ContactProf. Simon Pearce
Newcastle University
Outcome results
None listed