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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Affiris AG
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Number of patients who withdraw due to Adverse Events (AEs)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 30 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
- •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)
结局指标
主要结局
Number of patients who withdraw due to Adverse Events (AEs)
时间窗: 12 months
Physical Examination
时间窗: 12 months
New findings or change in pre-existing findings assessed in physical examinations over time (study period)
Body mass
时间窗: 12 months
Change of Body mass over time (study period)
Occurrence of Adverse Events and Serious Adverse Events
时间窗: 12 months
Evaluation of Adverse Events and Serious Adverse Events in regards to autoimmune reactions
Vital signs
时间窗: 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).
Clinical significance/ changes in laboratory parameters over time (study period)
时间窗: 12 months
Laboratory assessment includes hematology, biochemistry, coagulation, serology and urinanalysis
Safety related evaluation of MRI results of patients' brain after visit 5 and visit 8 compared to baseline
时间窗: 12 months
Safety measures will e.g. include the occurrence of inflammatory reactions (meningoencephalitis), new/changed hemorrhages and lacunar infarcts.
Neurological Examination
时间窗: 12 months
New findings or change in pre-existing findings assessed in neurological examinations over time (study period)
次要结局
- 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)