Prospective 24-week, Double-blind, Randomised, Placebo-controlled, Multicenter Study Evaluating Safety and Change in Efficacy-related Surrogate Parameters in Patients With Dementia of the Alzheimer's Type Under Treatment With Increasing Dosages of Intravenous Immunoglobulin (Octagam 10%)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Octapharma
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Change in the Area Under the Curve of Plasma Aβ1-40 in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion
研究概览
简要总结
This study evaluated the effect of 6 or 12 infusions of different doses of octagam (intravenous immunoglobulin [IVIG]) 10% on the reduction of amyloid beta peptide (Aβ) in cerebral spinal fluid (CSF) and on the increase of Aβ in blood plasma in patients with mild to moderate Alzheimer's disease.
详细描述
Participants received 12 infusions of 0.1 g/kg, 0.25 g/kg, or 0.4 g/kg body weight octagam 10% at 2-week intervals (±3 days) or 6 infusions of 0.2 g/kg, 0.5 g/kg, or 0.8 g/kg body weight octagam 10% at 4-week intervals (±5 days). The effect of the infusions on the reduction of Aβ peptide in CSF and the increase of Aβ peptide in blood plasma was evaluated.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Probable Alzheimer's Disease (AD) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
- •Age of 50 to
- •Mini-mental State Examination (MMSE) score of 16 to
- •Sufficient language skills for testing.
- •Sufficient vision and hearing for testing.
- •Modified Hachinski-Rosen Score <
- •Magnetic resonance imaging (MRI) of the head consistent with the diagnosis of AD.
- •Caregiver available with contact at least 4 days per week for greater than 1 hour.
- •Outpatient status or assisted living.
- •Post-menopause (women) as evidenced by lack of menstruation for at least 12 consecutive months or by having bilateral oophorectomy.
- •Stable doses of approved AD medication(s) for at least 3 months prior to screening (eg, acetylcholine esterase (AChE) inhibitors, memantine).
- •Normal vital signs or clinically insignificant, if outside normal limits.
- •Laboratory findings within normal limits or clinically insignificant, if outside normal limits.
- •Normal electrocardiogram (ECG) or clinically not significant, if outside normal limits.
排除标准
- •Other causes of dementia (eg, vascular dementia, Lewy-body dementia, fronto-temporal dementia, Creutzfeldt-Jacob disease, Huntington's disease, Parkinson's disease).
- •History of or present significant other diseases of the central nervous system (eg, brain tumor, normal pressure hydrocephalus, Parkinson's Disease, stroke, severe brain trauma, brain surgery, epilepsy, encephalitis).
- •Geriatric depression scale score > 7 (short form with scale from 0 to 15).
- •Present significant psychiatric disorder (eg, major depression).
- •History of psychosis or hallucinations.
- •Mental retardation.
- •Unstable medical disease in the opinion of the investigator.
- •Insulin dependent diabetes mellitus.
- •Acute infectious disease.
- •Vitamin B12 deficiency unless on stable replacement therapy for at least 3 months is acceptable.
- •Unstable thyroid dysfunction.
- •Uncontrolled hypertension.
- •Severe liver or kidney disease.
- •Major surgery within 3 months prior to screening.
- •Prohibited medications: Antiepileptic drugs, antipsychotics (but allowed for treatment of acute episodes), antiparkinson agents, anticholinergic drugs, selegiline, monoamine oxidase inhibitors (MAOI), tricyclics, immunosuppressive medications, anti-histamines (unless on a stable dose for at least 3 months or used for treatment of acute episodes), benzodiazepines (but allowed for treatment of acute episodes), and lithium.
- •Antidepressants are permitted, if on a stable dose for at least 3 months and without significant anticholinergic side-effects.
- •Peripheral venous conditions which impair establishing regular venous access for infusions.
- •Potential reasons that patient may become non-evaluable during the study (eg, planned moving into a nursing home, but assisted living is acceptable).
- •Peripheral venous conditions, which impair establishing regular venous access for infusions.
- •Known IgA deficiency with antibodies to IgA.
- •History of hypersensitivity to blood or plasma derived products, or any component of octagam 10%, such as maltose.
- •Medical conditions which interfere with protein catabolism (eg, nephrotic syndrome).
- •Known blood hyperviscosity or other hypercoagulable states.
- •Deep vein thrombosis within preceding 4 years.
- •Symptomatic stroke.
- •Transient ischemic attack (TIA) within preceding 2 years.
- •Participation in another drug trial within the previous 3 months before screening.
- •Participation in immunological treatment studies of AD other than with intravenous immunoglobulin (IGIV) within the previous 6 months before screening.
- •IGIV use in the previous 6 months.
- •Live viral vaccination within the last month before study entry.
- •Not eligible for lumbar puncture (anticoagulant therapy, coagulation disorders, severe spinal alterations).
- •Patients with a past or present history of drug abuse or alcohol abuse within the preceding 5 years.
- •Patients with any condition that would make the patient, in the opinion of the Investigator, unsuitable for the study.
研究组 & 干预措施
Placebo every 2 weeks
Participants received placebo intravenously every 2 weeks for 24 weeks (total of 12 infusions).
干预措施: Placebo (Drug)
0.1 g/kg octagam 10% every 2 weeks
Participants received 0.1 g/kg octagam 10% intravenously every 2 weeks for 24 weeks (total of 12 infusions).
干预措施: octagam 10% (Biological)
0.25 g/kg octagam 10% every 2 weeks
Participants received 0.25 g/kg octagam 10% every 2 weeks for 24 weeks (total of 12 infusions).
干预措施: octagam 10% (Biological)
0.4 g/kg octagam 10% every 2 weeks
Participants received of 0.4 g/kg octagam 10% every 2 weeks for 24 weeks (total of 12 infusions).
干预措施: octagam 10% (Biological)
Placebo every 4 weeks
Participants received placebo intravenously every 4 weeks for 20 weeks (total of 6 infusions).
干预措施: Placebo (Drug)
0.2 g/kg octagam 10% every 4 weeks
Participants received 0.2 g/kg octagam 10% intravenously every 4 weeks for 20 weeks (total of 6 infusions).
干预措施: octagam 10% (Biological)
0.5 g/kg octagam 10% every 4 weeks
Participants received 0.5 g/kg octagam 10% every 4 weeks for 20 weeks (total of 6 infusions).
干预措施: octagam 10% (Biological)
0.8 g/kg octagam 10% every 4 weeks
Participants received of 0.8 g/kg octagam 10% every 4 weeks for 20 weeks (total of 6 infusions).
干预措施: octagam 10% (Biological)
结局指标
主要结局
Change in the Area Under the Curve of Plasma Aβ1-40 in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion
时间窗: Week 22 to Week 24 for participants who received infusions every 2 weeks and Week 20 to Week 24 participants who received infusions every 4 weeks
For participants who received infusions every 2 weeks, plasma samples were collected at the trough level at Week 22 and on Days 1, 4, 7, and 14 after Week 22. For participants who received infusions every 4 weeks, plasma samples were collected at the trough level at Week 20 and on Days 1, 4, 7, 14, 21, and 28 after Week 20. Samples for determining Aβ1-40 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).
次要结局
- Change in the Area Under the Curve of Plasma Anti-Aβ Autoantibodies in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion(Week 22 to Week 24 for participants who received infusions every 2 weeks and Week 20 to Week 24 participants who received infusions every 4 weeks)
- Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion(Baseline to Week 23 Day 2 for participants who received infusions every 2 weeks and Baseline to Week 21 Day 2 for participants who received infusions every 4 weeks)
- Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion(Baseline to Week 23 Day 2 for participants who received infusions every 2 weeks and Baseline to Week 21 Day 2 for participants who received infusions every 4 weeks)
- Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion(Baseline to Week 23 Day 2 for participants who received infusions every 2 weeks and Baseline to Week 21 Day 2 for participants who received infusions every 4 weeks)
- Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24(Baseline to Week 24)
- Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24(Baseline to Week 24)
- Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24)(Baseline to Week 24)
- Change in the Area Under the Curve of Plasma Aβ1-42 in the 2 or 4 Weeks After the Last Treatment Infusion From the Trough Level Prior to the Last Treatment Infusion(Week 22 to Week 24 for participants who received infusions every 2 weeks and Week 20 to Week 24 participants who received infusions every 4 weeks)
- Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24)(Baseline to Week 24)
- Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24(Baseline to Week 24)
- Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24(Baseline to Week 24)
- Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24(Screening to Week 24)
- Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24(Baseline to Week 24)