Rescue of Addison’s disease 2

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2012-001682-33-GB
• Date of registration: 15/06/2012
• Prospective Registration: Yes
• Primary sponsor: Newcastle upon Tyne Hospitals NHS Foundation Trust
• Public title: Rescue of Addison’s disease 2
• Scientific title: Combined Immunotherapy and Trophic Adrenocortical Stimulation in New Onset Autoimmune Addison’s Disease - Rescue of Addison’s disease 2 (RADS2)
• Date of first enrolment: 06/09/2012
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001682-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

United Kingdom

Contacts

• Name: Prof. Simon Pearce
• Affiliation: Newcastle University

• Name: Prof. Simon Pearce
• Affiliation: Newcastle University

Key inclusion & exclusion criteria

Inclusion criteria:
- Clear evidence of adrenocortical failure with subnormal cortisol response to 250?g IV synacthen (peak cortisol <300nmol/l) plus either clinical or biochemical evidence to confirm elevated ACTH, or evidence of mineralcorticoid insufficiency
- Basal or ACTH stimulated serum 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:
- 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

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: 10014698 - Endocrine disorders
MedDRA version: 16.1 Level: LLT Classification code 10001342 Term: Adrenal cortical hypofunction System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Trade Name: Mabthera infusion
Product Name: Mabthera Infusion
Product Code: Rituximab
Pharmaceutical Form: Concentrate for solution for infusion

Trade Name: Solu-Medrone
Product Name: Solu-Medrone
Product Code: Methylprednisolone
Pharmaceutical Form: Powder for injection

Trade Name: Synacthen Depot
Product Name: Synacthen Depot
Product Code: Tetracosactide acetate
Pharmaceutical Form: Suspension for injection

Primary Outcome(s)

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?

Timepoint(s) of evaluation of this end point: 48 weeks post first treatment

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?

Primary end point(s): Peak serum cortisol in response to IM synacthen testing at 48 weeks.

Secondary Outcome(s)

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

Secondary ID(s)

6176/RADS2

ISRCTN20220821

Source(s) of Monetary Support

Medical Research Council

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 29/03/2019
• Date Completed: 16/05/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-001682-33/results