Clinical trial NCT02270489: Study Assessing Safety and Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early MSA
Official title: A Randomized, Placebo-controlled, Parallel Group, Patient-blind, Phase I Study Assessing the Safety and Exploring the Immunogenicity/Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early Multiple System Atrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple System Atrophy
Neurodegenerative Diseases
Lead sponsor: Affiris AG
Sponsor class: INDUSTRY
Collaborators: name: University Hospital, Bordeaux
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Forschungszentrum Juelich
name: University Hospital, Toulouse
First posted: 2014-10-21
Enrollment: 30
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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)

Primary outcomes:
measure: Number of patients who withdraw due to Adverse Events (AEs)
timeFrame: 12 months
measure: Occurrence of Adverse Events and Serious Adverse Events
timeFrame: 12 months
measure: Physical Examination
timeFrame: 12 months
measure: Vital signs
timeFrame: 12 months
measure: Safety related evaluation of MRI results of patients' brain after visit 5 and visit 8 compared to baseline
timeFrame: 12 months
measure: Clinical significance/ changes in laboratory parameters over time (study period)
timeFrame: 12 months
measure: Body mass
timeFrame: 12 months
measure: Neurological Examination
timeFrame: 12 months
Secondary outcomes:
measure: Immunological activity of AFFITOPE® vaccines PD01A and PD03A.
timeFrame: 12 months
measure: Change in motor symptoms at Visit 5 and Visit 8 compared to baseline
timeFrame: 12 months
measure: Change in non-motor symptoms at Visit 5 and Visit 8 compared to baseline
timeFrame: 12 months
Other outcomes:
Locations:
city: Bordeaux Cedex
country: France
facility: University Hospital Bordeaux (Pellegrin Hospital)
city: Toulouse Cedex 9
country: France
facility: University Hospital Toulouse
Study officials:
affiliation: University Hospital Bordeaux (Pellegrin Hospital), Bordeaux 33076, France
name: Wassilios Meissner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meissner WG, Traon AP, Foubert-Samier A, Galabova G, Galitzky M, Kutzelnigg A, Laurens B, Luhrs P, Medori R, Peran P, Sabatini U, Vergnet S, Volc D, Poewe W, Schneeberger A, Staffler G, Rascol O; AFF009 Study Investigators. A Phase 1 Randomized Trial of Specific Active alpha-Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy. Mov Disord. 2020 Nov;35(11):1957-1965. doi: 10.1002/mds.28218. Epub 2020 Sep 3.