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
- 2
- 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)
研究组 & 干预措施
AFFITOPE® PD01A + Adjuvant
4 injections of 75µg AFFITOPE® PD01A/ adjuvanted, once every 4 weeks
1 boost immunization 36 weeks after first injection
干预措施: AFFITOPE® PD01A + Adjuvant (Biological)
AFFITOPE® PD03A + Adjuvant
4 injections of 75µg AFFITOPE® PD03A/ adjuvanted, once every 4 weeks
1 boost immunization 36 weeks after first injection
干预措施: AFFITOPE® PD03A + Adjuvant (Biological)
Adjuvant without active component
4 injections of Placebo once every 4 weeks
1 administration 36 weeks after first injection
干预措施: Adjuvant without active component (Biological)
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)