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

NCT02270489 | Completed Phase 1 DMC

• 2 other identifiers: AFFiRiS 0092014-000567-40
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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).

Conditions

Multiple System Atrophy; Neurodegenerative Diseases

Outcome Measures

Primary Outcomes (8)

• Number of patients who withdraw due to Adverse Events (AEs)

  12 months

• Occurrence of Adverse Events and Serious Adverse Events

  Evaluation of Adverse Events and Serious Adverse Events in regards to autoimmune reactions

  12 months

• Physical Examination

  New findings or change in pre-existing findings assessed in physical examinations over time (study period)

  12 months

• Vital signs

  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).

  12 months

• Safety related evaluation of MRI results of patients' brain after visit 5 and visit 8 compared to baseline

  Safety measures will e.g. include the occurrence of inflammatory reactions (meningoencephalitis), new/changed hemorrhages and lacunar infarcts.

  12 months

• Clinical significance/ changes in laboratory parameters over time (study period)

  Laboratory assessment includes hematology, biochemistry, coagulation, serology and urinanalysis

  12 months

• Body mass

  Change of Body mass over time (study period)

  12 months

• Neurological Examination

  New findings or change in pre-existing findings assessed in neurological examinations over time (study period)

  12 months

Secondary Outcomes (3)

• Immunological activity of AFFITOPE® vaccines PD01A and PD03A.

  12 months

• Change in motor symptoms at Visit 5 and Visit 8 compared to baseline

  12 months

• Change in non-motor symptoms at Visit 5 and Visit 8 compared to baseline

  12 months

Study Arms (3)

AFFITOPE® PD01A + Adjuvant

EXPERIMENTAL

4 injections of 75µg AFFITOPE® PD01A/ adjuvanted, once every 4 weeks 1 boost immunization 36 weeks after first injection

Biological: AFFITOPE® PD01A + Adjuvant

AFFITOPE® PD03A + Adjuvant

EXPERIMENTAL

4 injections of 75µg AFFITOPE® PD03A/ adjuvanted, once every 4 weeks 1 boost immunization 36 weeks after first injection

Biological: AFFITOPE® PD03A + Adjuvant

Adjuvant without active component

PLACEBO COMPARATOR

4 injections of Placebo once every 4 weeks 1 administration 36 weeks after first injection

Biological: Adjuvant without active component

Interventions

AFFITOPE® PD01A + Adjuvant BIOLOGICAL

s.c. injection

AFFITOPE® PD01A + Adjuvant

AFFITOPE® PD03A + Adjuvant BIOLOGICAL

s.c. injection

AFFITOPE® PD03A + Adjuvant

Adjuvant without active component BIOLOGICAL

s.c. injection

Adjuvant without active component

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Affiris AG: lead
• University Hospital, Bordeaux: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Forschungszentrum Juelich: collaborator
• University Hospital, Toulouse: collaborator

Study Sites (2)

University Hospital Bordeaux (Pellegrin Hospital)

Bordeaux, 33076, France

Location

University Hospital Toulouse

Toulouse, 31059, France

Location

Related Publications (1)

• 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.

  PMID: 32882100 DERIVED

MeSH Terms

Conditions

Multiple System Atrophy; Neurodegenerative Diseases

Interventions

Adjuvants, Pharmaceutic

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies

Intervention Hierarchy (Ancestors)

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

Study Officials

• Wassilios Meissner, MD, PhD

  University Hospital Bordeaux (Pellegrin Hospital), Bordeaux 33076, France

  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: September 4, 2014
• First Posted: October 21, 2014
• Study Start: December 11, 2014
• Primary Completion: April 18, 2017
• Study Completion: April 18, 2017
• Last Updated: June 5, 2017

Record last verified: 2017-06

Locations

FR (2)