study assessing safety and therapeutic activity of affitope® pd01a and pd03a in patients with early msa

Conditions: Multiple System Atrophy; Neurodegenerative Diseases

Summary: this is a randomized controlled parallel group phase i study to investigate the safety and immunological/ therapeutic activity of two new vaccines, affitope® pd01a and affitope® pd03a, given to patients with early multiple system atrophy (msa). in total 30 patients are planned to be enrolled in the study: 12 patients in each treatment arm who will receive either 75µg affitope® pd01a (with adjuvant) or 75µg affitope® pd03a (with adjuvant) and 6 patients in the control group who will receive the reference substance (placebo). over a study duration of 52 weeks, the study participants will receive 4 injections as basic immunization in a 4-weekly interval and 1 boost immunization 36 weeks after the first injection. male and female patients aged 30 to 75 years can participate in the trial. 2 study sites in france (bordeaux and toulouse) will be involved. aff009 is part of the project sympath funded by the european commission (fp7-health-2013-innovation-1 project; n° health-f4-2013-602999).


Eligibility criteria:
inclusion criteria: * possible or probably msa diagnosis (msa-p or msa-c) according to gilman 2008 consensus criteria * onset of msa symptoms less than 4 years * participants with an anticipated survival of at least 3 years in the opinion of the pi * written informed consent obtained prior to study entry * msa patient \> 30 and \< 75 years of age at time of study entry * female patients of childbearing potential using a medically accepted contraceptive method * stable medication for msa symptoms (levodopa, dopamine agonists, midodrine, fludrocortisone, monoamine oxidase-b and catechol-o-methyltransferase inhibitors; antidepressants, laxatives, nsaids or paracetamol as basic medication for pain in the musculoskeletal system) exclusion criteria: * pregnant or lactating women * sexually active women of childbearing potential not using a medically accepted birth control method * patients with dementia (moca at screening \< 21) * speech impairment as assessed by a score of ≥ 3 on umsars question 1 * swallowing impairment as assessed by a score of ≥ 3 on umsars question 2 * impairment in ambulation as assessed by a score of ≥ 3 on umsars question 7 * history or evidence of any other central nervous system disorder like stroke, angioma and other relevant neurological diseases * history of malignancy other than skin cancer during the last 5 years (if considered to be cured, patient might be included) * active or passive vaccination 4 weeks before the first vaccination on day 0 and during the main study period ending on day 280. emergency vaccinations are acceptable * use of any other investigational or non-registered drug or vaccine in addition to the study vaccine during the entire study period * subjects participating or have participated in another interventional clinical trial within 60 days prior to baseline * blood donation within 4 weeks prior to first vaccination. * history of autoimmune diseases, severe hypersensitivity reactions and anaphylaxis, allergic bronchial asthma and severe allergic rhinoconjunctivitis * known hypersensitivity or allergic reaction to one of the components of the vaccine * a family history of congenital or hereditary immunodeficiency * administration of chronic (defined as more than 14 days) immunosuppressant or other immune-modifying drugs within six months before first vaccination and during the entire study period. for corticosteroids like prednisone or equivalent ≥ 0.05 mg/kg/day. topical and inhaled steroids are allowed * intake of non steroidal anti-inflammatory drugs (nsaids) or paracetamol more than the basic medication for pain in the musculoskeletal system within three days prior to a vaccination with affitope® pd01a or affitope® pd03a or placebo * if a patient shows an acute febrile infection (≥ 37.8° celsius) on the day of vaccination, administration of investigational medicinal product (imp) should be postponed until resolution of the infection * infection with the human immunodeficiency virus (hiv, a negative test result within 30 days before screening is acceptable), hepatitis b (hbsag) or hepatitis c * significant systemic illness (e.g. chronic renal failure, chronic liver disease, poorly controlled diabetes, poorly controlled congestive heart failure and/or other deficiencies), if considered relevant by the investigator * venous status rendering it impossible to place an i.v. access * contraindications for mri and lumbar puncture * not able to understand and comply with protocol requirements, instructions, protocol-stated restrictions * unwilling to provide informed consent. exceptions for patients who are physically not able to provide written informed consent (e.g. legal representative, consent via voce with witness)