Study Assessing Tolerability and Safety and Exploring the Immunogenicity and Therapeutic Activity of AFFITOPE® PD01A in PD-GBA Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 15 August 2016
• Main ID: NCT02758730
• Date of registration: 26/04/2016
• Prospective Registration: No
• Primary sponsor: Affiris AG
• Public title: Study Assessing Tolerability and Safety and Exploring the Immunogenicity and Therapeutic Activity of AFFITOPE® PD01A in PD-GBA Patients
• Scientific title: A Randomized, Placebo-controlled, Parallel Group, Patient-blind, Single-center Phase I Pilot Study Assessing Tolerability and Safety and Exploring the Immunogenicity and Therapeutic Activity of AFFITOPE® PD01A, a New Vaccine Against Alpha-synuclein, in Patients With PD-GBA
• Date of first enrolment: November 2015
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT02758730
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Germany

Contacts

• Name: Thomas Gasser, Prof. Dr.
• Affiliation: University Hospital Tübingen, 72076 Tübingen, Germany

Key inclusion & exclusion criteria

Inclusion Criteria:

- Confirmed diagnosis of Parkinson's disease and confirmed carrier status for a
heterozygous GBA mutation (PDGBA)

- Individuals who present in Hoehn&Yahr Stages I/II/III and fulfill the United Kingdom
Parkinson's Disease Society Brain Bank Criteria

- Confirmed carrier status for a heterozygous GBA mutation (PDGBA)-The result of the
MRI scan of the patient's brain has to be consistent with the diagnosis of PD

- Written informed consent signed and dated by the patient and, preferentially, the
caregiver (caregiver is not mandatory)

- Age between 40 and 80

- In the investigator's opinion, does not have visual or auditory impairments that
would reduce the patients' ability to complete study questionnaires or be unable to
receive instructions for these

- Female patients of childbearing potential are eligible if they use a medically
accepted contraceptive method

- A potential participant treated with conventional PD therapies must be on stable
doses for at least 3 months prior to Visit 1 and during the entire trial period

- Accepted PD medications include the following: levodopa (alone or in combination with
benserazide, carbidopa), catechol-O-methyltransferase (COMT) inhibitors (entacapone,
tolcapone), amantadine, non-ergot dopamine agonists (pramipexol, ropinirol,
rotigotine), monoamine oxidase-B (MAO-B) inhibitors (rasagiline, selegiline) and
anticholinergic medication

- A potential participant should be on stable doses of all medications he/she is taking
because of consisting illnesses according to medical history (except PD therapies,
these will be recorded separately) for at least 30 days prior to Visit 1 if
considered relevant by the investigator

- Able to communicate well with the investigator, to understand and comply with the
requirements of the study

Exclusion Criteria:

- Pregnant women

- Sexually active women of childbearing potential who are not using a medically
accepted birth control method

- Participation in another clinical trial within 3 months before Visit 1

- History of questionable compliance to visit schedule; patients not expected to
complete the clinical trial

- Presence or history of allergy to components of the vaccine if considered relevant by
the investigator

- Contraindication for MRI imaging such as metallic implants (e.g. endoprosthesis,
stents, cardiac pacemakers) which are not MR compatible at 3.0 Tesla with the given
MR protocol, other foreign metal bodies (e.g. bullets, metal splinters, e.g.) or
claustrophobia

- Missing agreement to be informed about incident findings and consultation of a
neuroradiologist

- Contraindication for PET, that is, pregnancy and breast feeding.

- Ongoing participation in other interventional studies or clinical trials using
radiotracers

- Dementia according to Diagnostic and Statistical Manual (DSM) IV criteria

- History and/or presence of autoimmune disease, if considered relevant by the
investigator

- Recent (=3 years since last specific treatment) history of cancer (Exceptions:
non-melanoma skin cancer, intraepithelial cervical neoplasia)

- Active infectious disease (e.g., Hepatitis B, C)

- Presence and/or history of Immunodeficiency (e.g., HIV)

- Significant systemic illness (e.g., chronic renal failure, chronic liver disease,
poorly controlled diabetes, poorly controlled congestive heart failure, other
deficiencies), if considered relevant by the investigator

- History of significant psychiatric illness such as schizophrenia, bipolar affective
disorder or psychotic depression

- Parkinson-like disease secondary to drug therapy side effects (e.g., due to exposure
to medications that deplete dopamine [reserpine, tetrabenazine] or block dopamine
receptors [neuroleptics, antiemetics])

- Parkinson-plus syndromes (e.g., multiple system atrophy (MSA), progressive
supranuclear palsy (PSP)), Dementia with Lewy Bodies (DLB)

- Heredodegenerative disorders other than PDGBA, evidence for other genetic forms of PD
(e.g. LRRK2, Parkin gene mutations)

- Alcoholism or substance abuse within the past year (alcohol or drug intoxication)

- Prior and/or current treatment with experimental immunotherapeutics including
Intravenous Immunoglobulin (IVIG)

- Prior and/or current treatment with immune modulating drugs:

1. Interleukins, Interferons, Tumor Necrosis Factor (TNF) and analogues, colony
stimulating factor compounds

2. Ciclosporin, Tacrolimus, Sirolimus and analogues

3. Cytostatic drugs and certain DMARD for rheumatoid arthritis (and similar
autoimmune disorders) (e.g. Cyclophosphamid, Azathioprin, methotrexate,
sulfasalazine, leflunomide, sodium aurothiomalate (Gold), cyclosporin) and
analogues

4. Systemic (gluco)corticoid therapy

5. All antibody therapies (e.g., anti cluster of differentiation 3 (CD3), anti
cluster of differentiation 25 (CD25) or also anti-lymphocyte globulins) that
might modulate, enhance or weaken an immune response

- Change in dose of standard treatments for PD within 3 months prior to Visit 1

- Change in dose of previous and current medications which the patient is taking
because of consisting illnesses according medical history (except PD therapies, these
will be recorded separately) within the last 30 days prior to Visit 1, if clinically
relevant

- Treatment with deep brain stimulation

- Venous status rendering it impossible to place an i.v. access



Age minimum: 40 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Parkinson's Disease

Intervention(s)

Biological: AFFITOPE® PD01A + Adjuvant

Biological: Adjuvant without active component

Primary Outcome(s)

Occurrence of unsolicited non-serious AEs within four weeks after the vaccinations [Time Frame: 12 weeks (week 0 to 12)]

Occurrence of any Grade 3 or higher AEs possibly, probably or definitely related to the study vaccine within 4 weeks after the vaccinations [Time Frame: 12 weeks (week 0 to 12)]

Occurrence of any Serious Adverse Event (SAE) possibly, probably or definitely related to the study vaccine at any time during the study [Time Frame: 52 weeks]

Number of patients who withdraw due to Adverse Events (AEs) and reason for withdrawal [Time Frame: 52 weeks]

Occurrence of solicited local AEs [Time Frame: up to 52 weeks]

Occurrence of solicited systemic AEs [Time Frame: up to 52 weeks]

Secondary Outcome(s)

Imaging efficacy variables at visit 6 (or EDV) compared to baseline [Time Frame: 52 weeks]

Immunological activity of AFFITOPE® vaccine PD01A over time (study period) [Time Frame: 52 weeks]

Biomarker data at visit 6 (or EDV) compared to baseline [Time Frame: 52 weeks]

Secondary ID(s)

2016-001462-28

AFF010

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University Hospital Tuebingen