Study Assessing Safety and Therapeutic Activity of AFFITOPE® PD01A and PD03A in Patients With Early MSA (AFF009)

• ClinicalTrials.gov Identifier: NCT02270489
• Recruitment Status: Completed
• First Posted: October 21, 2014
• Last Update Posted: June 5, 2017
• Sponsor: Affiris AG
• Collaborators: University Hospital, Bordeaux; Institut National de la Santé Et de la Recherche Médicale, France; Forschungszentrum Juelich; University Hospital, Toulouse
• Information provided by (Responsible Party): Affiris AG

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Multiple System Atrophy; Neurodegenerative Diseases	Biological: AFFITOPE® PD01A + Adjuvant; Biological: AFFITOPE® PD03A + Adjuvant; Biological: Adjuvant without active component	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 11, 2014
• Actual Primary Completion Date: April 18, 2017
• Actual Study Completion Date: April 18, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: AFFITOPE® PD01A + Adjuvant; 4 injections of 75µg AFFITOPE® PD01A/ adjuvanted, once every 4 weeks 1 boost immunization 36 weeks after first injection	Biological: AFFITOPE® PD01A + Adjuvant; s.c. injection
Experimental: AFFITOPE® PD03A + Adjuvant; 4 injections of 75µg AFFITOPE® PD03A/ adjuvanted, once every 4 weeks 1 boost immunization 36 weeks after first injection	Biological: AFFITOPE® PD03A + Adjuvant; s.c. injection
Placebo Comparator: Adjuvant without active component; 4 injections of Placebo once every 4 weeks 1 administration 36 weeks after first injection	Biological: Adjuvant without active component; s.c. injection

Outcome Measures

Primary Outcome Measures :

1. Number of patients who withdraw due to Adverse Events (AEs) [ Time Frame: 12 months ]
2. Occurrence of Adverse Events and Serious Adverse Events [ Time Frame: 12 months ]
   Evaluation of Adverse Events and Serious Adverse Events in regards to autoimmune reactions
3. Physical Examination [ Time Frame: 12 months ]
   New findings or change in pre-existing findings assessed in physical examinations over time (study period)
4. Vital signs [ Time Frame: 12 months ]
   Change in vital signs. The Evaluation includes the changes in blood pressure, heart rate, respiratory rate and Body temperature over time (measured at each visit).
5. Safety related evaluation of MRI results of patients' brain after visit 5 and visit 8 compared to baseline [ Time Frame: 12 months ]
   Safety measures will e.g. include the occurrence of inflammatory reactions (meningoencephalitis), new/changed hemorrhages and lacunar infarcts.
6. Clinical significance/ changes in laboratory parameters over time (study period) [ Time Frame: 12 months ]
   Laboratory assessment includes hematology, biochemistry, coagulation, serology and urinanalysis
7. Body mass [ Time Frame: 12 months ]
   Change of Body mass over time (study period)
8. Neurological Examination [ Time Frame: 12 months ]
   New findings or change in pre-existing findings assessed in neurological examinations over time (study period)

Secondary Outcome Measures :

1. Immunological activity of AFFITOPE® vaccines PD01A and PD03A. [ Time Frame: 12 months ]
   Titer of vaccination induced antibodies directed towards vaccine components, alpha- and beta synuclein
2. Change in motor symptoms at Visit 5 and Visit 8 compared to baseline [ Time Frame: 12 months ]
   Change in Motor symptoms: UMSARS II (Unified Multiple System Atrophy Rating Scale), CGI (Clinical Global Impression Improvement scale)
3. Change in non-motor symptoms at Visit 5 and Visit 8 compared to baseline [ Time Frame: 12 months ]
   Change in non-motor symptoms: UMSARS I and IV, GDS (Geriatric Depression Scale), COMPASS 31 (Composite Autonomic Symptom Score), MSA-QoL (MSA- Quality of life scale), MOCA (Montreal cognitive assessment), autonomic testing of cardiovascular function

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

France

University Hospital Bordeaux (Pellegrin Hospital)

Bordeaux Cedex, France, 33076

University Hospital Toulouse

Toulouse Cedex 9, France, 31059

Sponsors and Collaborators

Affiris AG

University Hospital, Bordeaux

Institut National de la Santé Et de la Recherche Médicale, France

Forschungszentrum Juelich

University Hospital, Toulouse

Investigators

• Principal Investigator: Wassilios Meissner, MD, PhD; University Hospital Bordeaux (Pellegrin Hospital), Bordeaux 33076, France

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Affiris AG
• ClinicalTrials.gov Identifier: NCT02270489
• Other Study ID Numbers: AFFiRiS 009; 2014-000567-40 ( EudraCT Number )
• First Posted: October 21, 2014
• Last Update Posted: June 5, 2017
• Last Verified: June 2017

Additional relevant MeSH terms:

Neurodegenerative Diseases; Multiple System Atrophy; Shy-Drager Syndrome; Atrophy; Pathological Conditions, Anatomical; Nervous System Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Hypotension; Vascular Diseases; Cardiovascular Diseases