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

Tracking Information

• First Submitted Date: September 4, 2014
• First Posted Date: October 21, 2014
• Last Update Posted Date: June 5, 2017
• Actual Study Start Date: December 11, 2014
• Actual Primary Completion Date: April 18, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 20, 2014)

• Number of patients who withdraw due to Adverse Events (AEs) [ Time Frame: 12 months ]
• 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
• Physical Examination [ Time Frame: 12 months ]
  New findings or change in pre-existing findings assessed in physical examinations over time (study period)
• 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).
• 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.
• Clinical significance/ changes in laboratory parameters over time (study period) [ Time Frame: 12 months ]
  Laboratory assessment includes hematology, biochemistry, coagulation, serology and urinanalysis
• Body mass [ Time Frame: 12 months ]
  Change of Body mass over time (study period)
• Neurological Examination [ Time Frame: 12 months ]
  New findings or change in pre-existing findings assessed in neurological examinations over time (study period)

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02270489 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 20, 2014)

• 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
• 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)
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment

Condition

• Multiple System Atrophy
• Neurodegenerative Diseases

Intervention

• Biological: AFFITOPE® PD01A + Adjuvant
  s.c. injection
• Biological: AFFITOPE® PD03A + Adjuvant
  s.c. injection
• Biological: Adjuvant without active component
  s.c. injection

Study Arms

• Experimental: AFFITOPE® PD01A + Adjuvant

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

  1 boost immunization 36 weeks after first injection

  Intervention: Biological: AFFITOPE® PD01A + Adjuvant
• Experimental: AFFITOPE® PD03A + Adjuvant

  4 injections of 75µg AFFITOPE® PD03A/ adjuvanted, once every 4 weeks

  1 boost immunization 36 weeks after first injection

  Intervention: Biological: AFFITOPE® PD03A + Adjuvant
• Placebo Comparator: Adjuvant without active component

  4 injections of Placebo once every 4 weeks

  1 administration 36 weeks after first injection

  Intervention: Biological: Adjuvant without active component

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 20, 2014): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 18, 2017
• Actual Primary Completion Date: April 18, 2017 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02270489
• Other Study ID Numbers: AFFiRiS 009; 2014-000567-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Affiris AG
• Study Sponsor: Affiris AG

Collaborators

• 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

• PRS Account: Affiris AG
• Verification Date: June 2017