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

NCT02758730 | Withdrawn Phase 1 DMC

• 2 other identifiers: AFF0102016-001462-28
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, placebo-controlled, parallel group, patient-blind, single-center phase I clinical trial of repeated once every 4 weeks administration by subcutaneous injection of AFFITOPE® PD01A, adsorbed to aluminium oxide in 30 patients with PD-GBA over a treatment period of 8 weeks. Patients will be randomized in a 2:1 ratio to two different treatment groups: A) 75 µg AFFITOPE® PD01A, adsorbed to aluminium oxide and B) placebo (= 1 mg aluminium oxide). Over a study duration of 52 weeks, each patient will receive 3 injections of AFFITOPE® PD01A or placebo during the participation in the clinical trial. Patients will either receive 75 µg AFFITOPE® PD01A adsorbed to 1 mg aluminium oxide or placebo (=1mg aluminium oxide). The treatment group consists of 20 PDGBA patients, the placebo group of 10 PDGBA patients. Male and female patients aged 40 to 80 years can participate in the trial. AFF010 is part of the project MULTISYN funded by the European Commission (FP7-HEALTH-2013-INNOVATION-1 project; N° HEALTH-F4-2013-602646).

Conditions

Parkinson's Disease

Keywords

GBA mutation

Outcome Measures

Primary Outcomes (6)

• Number of patients who withdraw due to Adverse Events (AEs) and reason for withdrawal

  52 weeks

• Occurrence of any Serious Adverse Event (SAE) possibly, probably or definitely related to the study vaccine at any time during the study

  52 weeks

• Occurrence of any Grade 3 or higher AEs possibly, probably or definitely related to the study vaccine within 4 weeks after the vaccinations

  12 weeks (week 0 to 12)

• Occurrence of solicited local AEs

  Injection site pain, erythema (redness), hyperthermia at injection site, itching, edema (swelling), induration \[hardening\], granuloma within 1 week (Day 1-7) after the vaccinations: Severity and duration

  up to 52 weeks

• Occurrence of solicited systemic AEs

  Headache, myalgia (muscle pain), fever, fatigue, nausea within 1 week (Day 1-7) after the vaccinations: Severity and duration.

  up to 52 weeks

• Occurrence of unsolicited non-serious AEs within four weeks after the vaccinations

  Severity, duration and relationship to vaccination

  12 weeks (week 0 to 12)

Secondary Outcomes (3)

• Immunological activity of AFFITOPE® vaccine PD01A over time (study period)

  52 weeks

• Imaging efficacy variables at visit 6 (or EDV) compared to baseline

  52 weeks

• Biomarker data at visit 6 (or EDV) compared to baseline

  52 weeks

Other Outcomes (5)

• Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) I, II, III and IV at visit 5 and visit 6 (or EDV) compared to baseline

  52 weeks

• Parkinson's Disease Quality of Life-39 (PDQ-39) at visit 5 and visit 6 (or EDV) compared to baseline

  52 weeks

• Investigator's global evaluation scale at visit 5 and visit 6 (or EDV)

  52 weeks

Study Arms (2)

AFFITOPE® PD01A + Adjuvant

EXPERIMENTAL

3 injections of 75µg AFFITOPE® PD01A/ adjuvanted, once every 4 weeks

Biological: AFFITOPE® PD01A + Adjuvant

Adjuvant without active component

PLACEBO COMPARATOR

3 injections of Placebo once every 4 weeks

Biological: Adjuvant without active component

Interventions

AFFITOPE® PD01A + Adjuvant BIOLOGICAL

s.c. injection

AFFITOPE® PD01A + Adjuvant

Adjuvant without active component BIOLOGICAL

s.c. injection

Adjuvant without active component

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Affiris AG: lead
• University Hospital Tuebingen: collaborator

Study Sites (1)

University Hospital Tübingen

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Thomas Gasser, Prof. Dr.

  University Hospital Tübingen, 72076 Tübingen, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: May 2, 2016
• Primary Completion: October 1, 2017
• Last Updated: August 5, 2016

Record last verified: 2016-08

Locations

DE (1)