Tolerability and Safety of Subcutaneous Administration of Two Doses of AFFITOPE® PD01A in Early Parkinson's Disease

Study Overview
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Brief Summary
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This is a phase I study to assess the tolerability and safety of 4 injections of two different doses of AFFITOPE® PD01A formulated with an adjuvant to patients with early Parkinson's disease in male and female patients aged 45 to 65 years (or age between 40 and 45 years if there is no evidence for genetic forms of the disease and the diagnosis of idiopathic Parkinson's disease was confirmed, after approval by Sponsor). One study site in Vienna (Austria) will be involved. Each patient's participation will last 1 year. In addition, up to 8 patients will be offered participation within an untreated control group.

Official Title
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A Randomized, Controlled, Parallel Group, Patient-blinded, Single-center, Phase I Pilot Study to Assess Tolerability and Safety of Repeated Subcutaneous Administration of Two Doses of AFFITOPE® PD01A Formulated With Adjuvant to Patients With Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Biological: AFFITOPE® PD01A
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent capability Early PD (≤ 4 years), Hoehn&Yahr Stages I/II and fulfill the UK Parkinson's Disease Society Brain Bank Criteria Brain magnetic resonance imaging (MRI) scan and DAT-SPECT scan are consistent with the diagnosis of PD Age between 45 and 65 years or age between 40 and 45 years if there is no evidence for genetic forms of the disease and the diagnosis of idiopathic PD was confirmed, after approval by Sponsor Caregiver able to attend all visits with patient Stable doses of medications (levodopa (+/- benserazide, carbidopa), COMT inhibitors (entacapone, tolcapone), non-ergot dopamine agonists (pramipexol, ropinirol, rotigotine), the MAO-B inhibitor rasagiline and amantadine are allowed) Exclusion Criteria: Women of childbearing potential without birth control or pregnant women Participation in another clinical trial Autoimmune disease or allergy to components of the vaccine Contraindications for MRI, DAT-SPECT, colonoscopy including biopsy or lumbar puncture Dementia History of cancer (Exceptions: basal cell carcinoma, intraepithelial cervical neoplasia) Active infectious disease Immunodeficiency Significant systemic illness or psychiatric illness Parkinson-like disease secondary to drug therapy side effects Parkinson-plus syndromes Heredodegenerative disorders Alcoholism or substance abuse Prior treatment with experimental immunotherapeutics for PD including IVIG, with immunosuppressive drugs or treatment with deep brain stimulation Venous status rendering it impossible to place an i.v. access

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: AFFITOPE® PD01A + Adjuvant<br>4 injections of 15µg AFFITOPE® PD01A/ adjuvanted, once every 4 weeks | Biological: AFFITOPE® PD01A<br>* s.c. injection<br>|
| Experimental: B: AFFITOPE® PD01A + Adjuvant<br>4 injections of 75µg AFFITOPE® PD01A/ adjuvanted, once every 4 weeks | Biological: AFFITOPE® PD01A<br>* s.c. injection<br>|
| Other: Control<br>Untreated control group | Other: Control<br>* Untreated control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability/Safety | Occurrence of any AE (including a clinical grading scale of AEs according to NCI-CTCAE Version 4.02 (2009) for assessments of AEs + toxicity and including a grading of local injection site reactions according to the FDA Guidance for Industry: Toxicity Scale for Healthy Adult and Adolescents Patients Enrolled in Preventive Vaccine Clinical Trials (2007)) Occurrence of any SAE Withdrawal criteria (number of patients who withdraw due to AEs/ reason for withdrawal) | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological | - Titer of vaccination induced antibodies directed towards vaccine components, alpha- and beta synuclein | 12 month | 
| Clinical Activity | Change in motor symptoms (MDS-UPDRS III) Change in non-motor PD symptoms (e.g.; MDS-UPDRS Ia, II, PDQ39, cognition) Change in biological and radiological markers (e.g. CSF alpha synuclein levels) | 12 month |