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

Affiris

Status and phase: Completed; Phase 1

Conditions: Multiple System Atrophy; Neurodegenerative Diseases

Treatments: Biological: AFFITOPE® PD01A + Adjuvant; Biological: AFFITOPE® PD03A + Adjuvant; Biological: Adjuvant without active component

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02270489

2014-000567-40 (EudraCT Number)

AFFiRiS 009

Details and patient eligibility

About

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).

Enrollment: 30 patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 3 patient groups, including a placebo group

AFFITOPE® PD01A + Adjuvant

Experimental group

Description:

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

Treatment:

Biological: AFFITOPE® PD01A + Adjuvant

AFFITOPE® PD03A + Adjuvant

Experimental group

Description:

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

Treatment:

Biological: AFFITOPE® PD03A + Adjuvant

Adjuvant without active component

Placebo Comparator group

Description:

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

Treatment:

Biological: Adjuvant without active component