Can suppressing the immune system with azathioprine slow down the progression of Parkinson's disease?

Phase 1

Conditions: Parkinson's disease
MedDRA version: 20.0Level: PTClassification code 10061536Term: Parkinson's diseaseSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2018-003089-14-GB

Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust and University of Cambridge

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 60

Inclusion Criteria

• Be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Aged 50 years or over
• Be a fluent English speaker
• Have a diagnosis of PD according to UKPDS Brain Bank Criteria
• Have a disease duration of <3 years
• Have a probability of poor outcome (postural instability/dementia/death) at 5 years from diagnosis =50% [28]
• Have adequate organ and marrow function, as defined below (measured within 42 days of first dose of trial medication):
o Haemoglobin = 110 g/L
o Platelet count = 130 x 109/L
o Neutrophil count = 1.5 x 109/L
o Renal Function- Creatinine clearance =50mL/min
o Hepatic function- Alanine aminotransferase (ALT) =2 times the institutional upper limit of normal (ULN) and total bilirubin =2 times the ULN.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

The presence of any of the following will preclude participant inclusion:
• Any use of immunomodulatory drugs such as azathioprine, mycophenolate, methotrexate, ciclosporin, cyclophosphamide within the last 12 months
• Any previous use of rituximab or alemtuzumab
• Previous treatment with corticosteroids for greater than 2 weeks, or any steroid use in the last 3 months
• Regular use of non-steroidal anti-inflammatory drugs including aspirin>75mg, naproxen, ibuprofen, meloxicam on more than 2 days per week.
• Known inflammatory or autoimmune disease
• Chronic or latent infection
• Active infection requiring the use of parenteral antimicrobial agents within 2 months prior to the first dose of study treatment.
• Skin malignancy or solid organ malignancy within the last 5 years.
• Current or previous haematological malignancy
• Positive test for HIV or hepatitis
• The inability to take or swallow oral medication
• Dementia according to Movement Disorder Society dementia criteria
• Thiopurine methyltransferase (TPMT) deficiency <10 pmol/h/mg Hb
• Lack of immunity to VZV
• Negative EBV IgG
• Chronic liver disease
• Renal impairment - creatinine clearance <50mL/min
• Concomitant use of allopurinol (increases risk of myelotoxicity)
• Any concurrent medical or psychiatric condition or disease (e.g. active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
• Receipt of live, attenuated vaccine within the last 30 days. Note: enrolled patients should not receive live, attenuated vaccine while receiving azathioprine nor within 30 days of last dose of azathioprine
• •Women of childbearing potential. Female patients must be surgically sterile or be postmenopausal.
oPostmenopausal is defined as spontaneous cessation of regular menses for at least 12 consecutive months or follicle-stimulating hormone (FSH) blood levels in the testing laboratory’s respective postmenopausal range with no alternative pathological or physiological cause.
•Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy and for 6 months after completion of trial drug
• Known hypersensitivity to azathioprine or its excipients
• Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before treatment protocol registration or is currently enrolled in an interventional investigational study.