Alzheimer's Disease
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGPlacebo
Commercially available 0.9% isotonic sodium chloride solution.
BIOLOGICALoctagam 10%
octagam 10% was supplied as ready-to-use solutions of human immunoglobulin.
Sponsors
Octapharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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 85. * Mini-mental State Examination (MMSE) score of 16 to 26. * Sufficient language skills for testing. * Sufficient vision and hearing for testing. * Modified Hachinski-Rosen Score \< 5. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | Baseline to Week 24 | Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively. |
| 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 | 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 Aβ1-42 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium). |
| 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 | 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 anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively. |
| 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 | Samples for determining Aβ1-40 and Aβ1-42 in cerebral spinal fluid were processed at a central laboratory using a commercially available kit from Meso Scale Discovery (MSD 96-Well Multi-Spot Human/Rodent (4G8) Abeta Triplex Ultra-Sensitive Assay; Rockville, MD, USA). |
| 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 | Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively. |
| 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 | Samples for determining tau and phosphorylated tau in cerebral spinal fluid were processed at a central laboratory using commercially available kits from Innogenetics NV (INNOTEST® hTau Ag, INNOTEST PHOSPHO-TAU (181P); Gent, Belgium). To measure phosphorylated tau, tau phosphorylated at threonine 181 (pTau181) was determined. |
| Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Baseline to Week 24 | Samples for determining Aβ1-40 and Aβ1-42 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium). |
| 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 | The ADAS cog consists of 11 items that assess cognitive areas that are often impaired in Alzheimer's disease, specifically learning (word list), naming (objects), following commands (1 to 5 elements), ideational praxis (mail a letter), constructional praxis (copy 4 figures), orientation (person, time and place), recognition memory (from a second word list), and remembering test instructions (from the recognition subtest). The test includes 3 additional subjective scales that assess spoken language ability, word finding difficulty, and comprehension. The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 to 70 with a higher score indicating greater cognitive impairment. A negative change score indicates improvement. |
| 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 | The ADAS-ADL consists of 23 questions that measure the ability of a person to perform basic activities of daily living, such as eating, walking, bathing, grooming, and dressing. The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 to 78 with a lower score indicating more impaired ability. A positive change score indicates improvement. |
| Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Baseline to Week 24 | A semi-structured interview was conducted by a physician, neuropsychologist, psychometrician, or certified study coordinator with the patient and a caregiver. Based on the results of the interview, the patient was rated on 6 domains of cognition and function: Memory, orientation, judgment/problem solving, community activities, home and hobbies, and personal care. Each domain is rated from 0 = no dementia; 0.5 = questionable dementia, mild cognitive impairment; 1 = mild dementia; 2 = moderate dementia; 3 = severe dementia. The total score ranges from 0 to 18 with a higher score indicating more dementia. A negative change score indicates improvement. |
| Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Screening to Week 24 | The volume of the whole brain and of the left and right hippocampus was measured using high-resolution structural coronal 3D heavily T1-weighted gradient-echo sequence magnetic resonance imaging. All evaluations were done centrally by Professor Frederik Barkhof at the Image Analysis Centre, VU Medical Center, Amsterdam, Netherlands. A negative change score indicates loss of brain volume. |
| Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Baseline to Week 24 | Cerebral glucose metabolism was measured in validated 3 dimensional statistic surface projection analysis (Cortex ID®, GE Healthcare), transversal/coronal/sagittal-slice analysis (HERMES BRASS), and voxel-wise whole brain analysis (SPM5) using \[18F\]fluorodeoxyglucose positron emission tomography. |
| Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Baseline to Week 24 | The MMSE test contains 30 questions that assess 8 cognitive domains (orientation to time, orientation to place, registration, attention and calculation, recall, language, repetition, and complex commands). The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 (severe impairment) to 30 (no impairment), with a higher score indicating a better mental status. A positive change score indicates improvement. |
Countries
United States
Participant flow
Recruitment details
The first patient was enrolled February 2, 2009. The last patient study visit was September 21, 2010. Patients were enrolled in this study from a variety of settings including private practice clinics and hospitals. There were 12 study sites, 5 in Germany and 7 in the United States.
Pre-assignment details
Qualified patients meeting all inclusion exclusion criteria and providing informed consent were enrolled into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Every 2 Weeks Participants received placebo intravenously every 2 weeks for 24 weeks (total of 12 infusions). | 7 |
| 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). | 6 |
| 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). | 7 |
| 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). | 7 |
| Placebo Every 4 Weeks Participants received placebo intravenously every 4 weeks for 20 weeks (total of 6 infusions). | 7 |
| 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). | 6 |
| 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). | 8 |
| 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). | 7 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 1 |
| Overall Study | Did Not Come to Study Visit | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Did Not Receive Study Medication | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal of Consent | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo Every 2 Weeks | 0.1 g/kg Octagam 10% Every 2 Weeks | 0.25 g/kg Octagam 10% Every 2 Weeks | 0.4 g/kg Octagam 10% Every 2 Weeks | Placebo Every 4 Weeks | 0.2 g/kg Octagam 10% Every 4 Weeks | 0.5 g/kg Octagam 10% Every 4 Weeks | 0.8 g/kg Octagam 10% Every 4 Weeks | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 72.6 Years STANDARD_DEVIATION 9.2 | 66.8 Years STANDARD_DEVIATION 5.5 | 68.3 Years STANDARD_DEVIATION 4.2 | 72.9 Years STANDARD_DEVIATION 5 | 71.4 Years STANDARD_DEVIATION 11.8 | 74.8 Years STANDARD_DEVIATION 5.5 | 65.9 Years STANDARD_DEVIATION 10.2 | 68.4 Years STANDARD_DEVIATION 8.6 | 70.0 Years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants | 24 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 4 Participants | 4 Participants | 2 Participants | 4 Participants | 5 Participants | 4 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 7 | 4 / 6 | 5 / 7 | 3 / 7 | 3 / 7 | 4 / 7 | 4 / 8 | 4 / 7 |
| serious Total, serious adverse events | 2 / 7 | 1 / 6 | 0 / 7 | 2 / 7 | 2 / 7 | 0 / 7 | 1 / 8 | 0 / 7 |
Outcome results
Primary
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
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).
Time frame: 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
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Every 2 Weeks | 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 | 161.20 (pg/mL)*days | Standard Deviation 93.9 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | 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 | -245.67 (pg/mL)*days | Standard Deviation 747.58 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | 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 | -122.50 (pg/mL)*days | Standard Deviation 478.31 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | 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 | -39.10 (pg/mL)*days | Standard Deviation 172.72 |
| Placebo Every 4 Weeks | 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 | 510.92 (pg/mL)*days | Standard Deviation 2395.8 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | 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 | -83.67 (pg/mL)*days | Standard Deviation 957.69 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | 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 | -755.38 (pg/mL)*days | Standard Deviation 2232.87 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | 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 | -262.92 (pg/mL)*days | Standard Deviation 671.37 |
Secondary
Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion
Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively.
Time frame: 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
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 0.38 RTU | Standard Deviation 3.72 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 0.22 RTU | Standard Deviation 1.83 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 1.86 RTU | Standard Deviation 1.93 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | -0.78 RTU | Standard Deviation 1.64 |
| Placebo Every 4 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 0.15 RTU | Standard Deviation 0.29 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 0.40 RTU | Standard Deviation 1.43 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 1.12 RTU | Standard Deviation 1.48 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Anti-Aβ Autoantibodies in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | 0.74 RTU | Standard Deviation 2.32 |
Secondary
Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion
Samples for determining Aβ1-40 and Aβ1-42 in cerebral spinal fluid were processed at a central laboratory using a commercially available kit from Meso Scale Discovery (MSD 96-Well Multi-Spot Human/Rodent (4G8) Abeta Triplex Ultra-Sensitive Assay; Rockville, MD, USA).
Time frame: 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
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 939.4 pg/mL | Standard Deviation 1670.8 |
| Placebo Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | 32.4 pg/mL | Standard Deviation 67 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 266.7 pg/mL | Standard Deviation 996 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | -8.7 pg/mL | Standard Deviation 38.2 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 10.6 pg/mL | Standard Deviation 1104 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | 9.7 pg/mL | Standard Deviation 54.7 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | -147.0 pg/mL | Standard Deviation 1067.9 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | 4.0 pg/mL | Standard Deviation 40.3 |
| Placebo Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 42.0 pg/mL | Standard Deviation 874 |
| Placebo Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | -5.2 pg/mL | Standard Deviation 36.3 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 561.7 pg/mL | Standard Deviation 1195.5 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | 18.8 pg/mL | Standard Deviation 40.3 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | 10.5 pg/mL | Standard Deviation 40.9 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 403.9 pg/mL | Standard Deviation 588.1 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-40 | 642.2 pg/mL | Standard Deviation 1171.3 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Aβ1-40 and Aβ1-42 in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Aβ1-42 | 24.7 pg/mL | Standard Deviation 43.2 |
Secondary
Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion
Samples for determining tau and phosphorylated tau in cerebral spinal fluid were processed at a central laboratory using commercially available kits from Innogenetics NV (INNOTEST® hTau Ag, INNOTEST PHOSPHO-TAU (181P); Gent, Belgium). To measure phosphorylated tau, tau phosphorylated at threonine 181 (pTau181) was determined.
Time frame: 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
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | 17.4 pg/mL | Standard Deviation 38.6 |
| Placebo Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | 0.60 pg/mL | Standard Deviation 7.5 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | 209.3 pg/mL | Standard Deviation 416 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | -3.17 pg/mL | Standard Deviation 14.66 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | -3.4 pg/mL | Standard Deviation 35.6 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | 0.43 pg/mL | Standard Deviation 3.6 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | -7.8 pg/mL | Standard Deviation 51.3 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | 2.60 pg/mL | Standard Deviation 4.98 |
| Placebo Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | -33.2 pg/mL | Standard Deviation 69.7 |
| Placebo Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | -1.33 pg/mL | Standard Deviation 10.05 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | -141.8 pg/mL | Standard Deviation 419.5 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | 3.33 pg/mL | Standard Deviation 21.23 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | -2.50 pg/mL | Standard Deviation 8.62 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | 1.3 pg/mL | Standard Deviation 86.7 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Tau | 131.3 pg/mL | Standard Deviation 301 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in Tau and Phosphorylated Tau in Cerebral Spinal Fluid 24-48 Hours After the Last Infusion | Phosphorylated tau | 10.17 pg/mL | Standard Deviation 19.28 |
Secondary
Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24
The ADAS cog consists of 11 items that assess cognitive areas that are often impaired in Alzheimer's disease, specifically learning (word list), naming (objects), following commands (1 to 5 elements), ideational praxis (mail a letter), constructional praxis (copy 4 figures), orientation (person, time and place), recognition memory (from a second word list), and remembering test instructions (from the recognition subtest). The test includes 3 additional subjective scales that assess spoken language ability, word finding difficulty, and comprehension. The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 to 70 with a higher score indicating greater cognitive impairment. A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 1.11 Units on a scale | Standard Deviation 4.1 |
| Placebo Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -0.62 Units on a scale | Standard Deviation 3.86 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.94 Units on a scale | Standard Deviation 7.27 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 2.06 Units on a scale | Standard Deviation 3.32 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.86 Units on a scale | Standard Deviation 4.75 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -2.14 Units on a scale | Standard Deviation 4.41 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.07 Units on a scale | Standard Deviation 4.43 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 3.67 Units on a scale | Standard Deviation 4.85 |
| Placebo Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 1.52 Units on a scale | Standard Deviation 5.67 |
| Placebo Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 0.93 Units on a scale | Standard Deviation 3.29 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 3.67 Units on a scale | Standard Deviation 3.85 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 4.17 Units on a scale | Standard Deviation 4.85 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 3.00 Units on a scale | Standard Deviation 9.37 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 1.54 Units on a scale | Standard Deviation 6.63 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 2.28 Units on a scale | Standard Deviation 5.06 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Assessment Scale, Cognitive Part (ADAS Cog) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 1.89 Units on a scale | Standard Deviation 8.71 |
Secondary
Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24
The ADAS-ADL consists of 23 questions that measure the ability of a person to perform basic activities of daily living, such as eating, walking, bathing, grooming, and dressing. The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 to 78 with a lower score indicating more impaired ability. A positive change score indicates improvement.
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 6.7 Units on a scale | Standard Deviation 4 |
| Placebo Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 1.9 Units on a scale | Standard Deviation 5 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.0 Units on a scale | Standard Deviation 5.4 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -1.5 Units on a scale | Standard Deviation 5.2 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 1.7 Units on a scale | Standard Deviation 2.8 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -4.1 Units on a scale | Standard Deviation 6.6 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -1.2 Units on a scale | Standard Deviation 3.5 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -6.5 Units on a scale | Standard Deviation 9.7 |
| Placebo Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.6 Units on a scale | Standard Deviation 8.5 |
| Placebo Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -1.8 Units on a scale | Standard Deviation 6 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -8.2 Units on a scale | Standard Deviation 11.8 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -4.3 Units on a scale | Standard Deviation 14.4 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 1.5 Units on a scale | Standard Deviation 8.2 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 1.8 Units on a scale | Standard Deviation 5 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -1.9 Units on a scale | Standard Deviation 3.5 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADAS-ADL) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -1.2 Units on a scale | Standard Deviation 3.3 |
Secondary
Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24
A semi-structured interview was conducted by a physician, neuropsychologist, psychometrician, or certified study coordinator with the patient and a caregiver. Based on the results of the interview, the patient was rated on 6 domains of cognition and function: Memory, orientation, judgment/problem solving, community activities, home and hobbies, and personal care. Each domain is rated from 0 = no dementia; 0.5 = questionable dementia, mild cognitive impairment; 1 = mild dementia; 2 = moderate dementia; 3 = severe dementia. The total score ranges from 0 to 18 with a higher score indicating more dementia. A negative change score indicates improvement.
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.67 Units on a scale | Standard Deviation 1.08 |
| Placebo Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -0.57 Units on a scale | Standard Deviation 1.57 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.25 Units on a scale | Standard Deviation 0.76 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 0.92 Units on a scale | Standard Deviation 2.15 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.21 Units on a scale | Standard Deviation 0.86 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 0.14 Units on a scale | Standard Deviation 1.28 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.60 Units on a scale | Standard Deviation 0.89 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 1.25 Units on a scale | Standard Deviation 1.97 |
| Placebo Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.36 Units on a scale | Standard Deviation 1.38 |
| Placebo Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | -1.50 Units on a scale | Standard Deviation 2.55 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.42 Units on a scale | Standard Deviation 1.36 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 0.83 Units on a scale | Standard Deviation 1.44 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 0.44 Units on a scale | Standard Deviation 1.92 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.50 Units on a scale | Standard Deviation 1.46 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 0.21 Units on a scale | Standard Deviation 1.52 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Clinical Dementia Ratio, Sum of Boxes (CDR-SOB) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,5,6,8,6) | 0.58 Units on a scale | Standard Deviation 1.66 |
Secondary
Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24
The MMSE test contains 30 questions that assess 8 cognitive domains (orientation to time, orientation to place, registration, attention and calculation, recall, language, repetition, and complex commands). The test is administered by a neuropsychologist, psychometrician, or certified study coordinator. The total score ranges from 0 (severe impairment) to 30 (no impairment), with a higher score indicating a better mental status. A positive change score indicates improvement.
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | 1.5 Units on a scale | Standard Deviation 2.1 |
| Placebo Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -0.7 Units on a scale | Standard Deviation 3 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -2.3 Units on a scale | Standard Deviation 3.5 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -2.2 Units on a scale | Standard Deviation 4.4 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.6 Units on a scale | Standard Deviation 3 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | 0.6 Units on a scale | Standard Deviation 2.5 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -2.0 Units on a scale | Standard Deviation 3.1 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -1.7 Units on a scale | Standard Deviation 2.3 |
| Placebo Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.7 Units on a scale | Standard Deviation 3 |
| Placebo Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -1.8 Units on a scale | Standard Deviation 5.5 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -1.2 Units on a scale | Standard Deviation 2.3 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -3.2 Units on a scale | Standard Deviation 3.3 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -1.8 Units on a scale | Standard Deviation 1.8 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.3 Units on a scale | Standard Deviation 2.8 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 12 (n=6,6,7,5,7,6,8,7) | -0.9 Units on a scale | Standard Deviation 2.4 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Baseline in the Mini Mental Status Examination (MMSE) Score at Week 12 and Week 24 | Week 24 (n=7,6,7,6,6,6,8,6) | -1.5 Units on a scale | Standard Deviation 3.1 |
Secondary
Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24
The volume of the whole brain and of the left and right hippocampus was measured using high-resolution structural coronal 3D heavily T1-weighted gradient-echo sequence magnetic resonance imaging. All evaluations were done centrally by Professor Frederik Barkhof at the Image Analysis Centre, VU Medical Center, Amsterdam, Netherlands. A negative change score indicates loss of brain volume.
Time frame: Screening to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -7.3 cm^3 | Standard Deviation 1.2 |
| Placebo Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -0.112 cm^3 | Standard Deviation 0.738 |
| Placebo Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -4.3 cm^3 | Standard Deviation 2.7 |
| Placebo Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -3.8 cm^3 | Standard Deviation 2.7 |
| Placebo Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -7.6 cm^3 | Standard Deviation 3.8 |
| Placebo Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.403 cm^3 | Standard Deviation 0.978 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -2.6 cm^3 | Standard Deviation 3.8 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -0.548 cm^3 | Standard Deviation 1.001 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.978 cm^3 | Standard Deviation 0.798 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -4.4 cm^3 | Standard Deviation 4.7 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -3.1 cm^3 | Standard Deviation 3.1 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.6 cm^3 | Standard Deviation 3 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.0 cm^3 | Standard Deviation 2.8 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -3.6 cm^3 | Standard Deviation 2.6 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -2.4 cm^3 | Standard Deviation 1.7 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.488 cm^3 | Standard Deviation 0.726 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.3 cm^3 | Standard Deviation 5.6 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -0.709 cm^3 | Standard Deviation 1.026 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -5.2 cm^3 | Standard Deviation 4.1 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -1.833 cm^3 | Standard Deviation 2.001 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -1.8 cm^3 | Standard Deviation 4.2 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -3.0 cm^3 | Standard Deviation 2.4 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.390 cm^3 | Standard Deviation 1.678 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -4.5 cm^3 | Standard Deviation 7.1 |
| Placebo Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.0 cm^3 | Standard Deviation 5 |
| Placebo Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -2.8 cm^3 | Standard Deviation 2.6 |
| Placebo Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -5.1 cm^3 | Standard Deviation 4.5 |
| Placebo Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | 0.533 cm^3 | Standard Deviation 0.481 |
| Placebo Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -0.875 cm^3 | Standard Deviation 0.78 |
| Placebo Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -4.8 cm^3 | Standard Deviation 4.2 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -1.8 cm^3 | Standard Deviation 1.6 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.363 cm^3 | Standard Deviation 1.752 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -2.8 cm^3 | Standard Deviation 3.9 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -7.4 cm^3 | Standard Deviation 4.3 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -0.528 cm^3 | Standard Deviation 1.873 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -5.3 cm^3 | Standard Deviation 2.4 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.096 cm^3 | Standard Deviation 1.004 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.9 cm^3 | Standard Deviation 7.7 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -0.177 cm^3 | Standard Deviation 1.219 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -1.5 cm^3 | Standard Deviation 3.6 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.5 cm^3 | Standard Deviation 4.6 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -4.8 cm^3 | Standard Deviation 5 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 24 (n=4,5,6,5,4,6,8,6) | -1.583 cm^3 | Standard Deviation 1.07 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -4.9 cm^3 | Standard Deviation 3.2 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Right hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -8.2 cm^3 | Standard Deviation 5 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 24 (n=4,6,6,5,5,6,8,6) | -6.2 cm^3 | Standard Deviation 3.7 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Whole brain - Week 12 (n=5,5,7,4,7,6,7,7) | -1.109 cm^3 | Standard Deviation 0.731 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change From Screening in Whole Brain and Hippocampal Volume at Week 12 and Week 24 | Left hippocampus - Week 12 (n=5,6,7,5,7,6,7,7) | -2.2 cm^3 | Standard Deviation 3.7 |
Secondary
Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24)
Samples for determining anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively.
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Every 2 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 109.7 RTU | Standard Deviation 284.8 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 74.3 RTU | Standard Deviation 35 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 163.9 RTU | Standard Deviation 136.6 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 310.2 RTU | Standard Deviation 193 |
| Placebo Every 4 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | -56.3 RTU | Standard Deviation 58.3 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 96.7 RTU | Standard Deviation 133.7 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 256.6 RTU | Standard Deviation 214.1 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Anti-Aβ Autoantibodies From Baseline to the End of the Study (Week 24) | 501.3 RTU | Standard Deviation 514.6 |
Secondary
Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24)
Samples for determining Aβ1-40 and Aβ1-42 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | 27.1 pg/mL | Standard Deviation 40.2 |
| Placebo Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | 4.1 pg/mL | Standard Deviation 3.8 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | 5.5 pg/mL | Standard Deviation 64.5 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -2.3 pg/mL | Standard Deviation 7.8 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | -0.3 pg/mL | Standard Deviation 22.1 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -4.5 pg/mL | Standard Deviation 6.3 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | -6.5 pg/mL | Standard Deviation 61.4 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -2.7 pg/mL | Standard Deviation 7.6 |
| Placebo Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | -6.0 pg/mL | Standard Deviation 23.8 |
| Placebo Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -2.0 pg/mL | Standard Deviation 4.8 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | -20.3 pg/mL | Standard Deviation 29.2 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -3.5 pg/mL | Standard Deviation 5.8 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -0.1 pg/mL | Standard Deviation 4.4 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | 15.7 pg/mL | Standard Deviation 29.7 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-40 | -30.5 pg/mL | Standard Deviation 42.3 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Change in Plasma Concentration of Aβ1-40 and Aβ1-42 From Baseline to the End of the Study (Week 24) | Aβ1-42 | -7.0 pg/mL | Standard Deviation 6.2 |
Secondary
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
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 anti-Aβ autoantibodies in blood plasma were processed at a central laboratory using a commercially available kit from DRG Instruments GmbH, (EIA-5099; Marburg, Germany) using methods established at the Department of Neurology, Philipps-University, Marburg, Germany (Professor Dr. med. Richard Dodel). The kit includes 6 standard concentrations of anti-Aβ antibody against which the results of the assay are compared. The standards contain 1, 5, 15, 30, 60, and 120 Relative Units (RTU) which contain 0.03, 0.17, 0.5, 1, 2, and 4 mg IgG/mL, respectively.
Time frame: 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
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Every 2 Weeks | 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 | 2829.0 RTU*days | Standard Deviation 3957.9 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | 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 | 358.3 RTU*days | Standard Deviation 435.8 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | 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 | 1862.5 RTU*days | Standard Deviation 1470.9 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | 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 | 2189.6 RTU*days | Standard Deviation 2289.3 |
| Placebo Every 4 Weeks | 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 | 196.6 RTU*days | Standard Deviation 1023 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | 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 | 849.4 RTU*days | Standard Deviation 2313.6 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | 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 | 6350.8 RTU*days | Standard Deviation 3464.9 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | 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 | 8494.9 RTU*days | Standard Deviation 2292.4 |
Secondary
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
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 Aβ1-42 in blood plasma were processed at a central laboratory using a commercially available kit from Innogenetics NV (INNO-BIA plasma Aβ forms; Gent, Belgium).
Time frame: 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
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Every 2 Weeks | 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 | 40.70 (pg/mL)*days | Standard Deviation 48.54 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | 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 | -8.92 (pg/mL)*days | Standard Deviation 61.71 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | 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 | -53.94 (pg/mL)*days | Standard Deviation 61.59 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | 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 | -17.00 (pg/mL)*days | Standard Deviation 23.67 |
| Placebo Every 4 Weeks | 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 | 50.13 (pg/mL)*days | Standard Deviation 233.87 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | 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 | -8.98 (pg/mL)*days | Standard Deviation 213.29 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | 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 | -191.58 (pg/mL)*days | Standard Deviation 456.83 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | 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 | -64.75 (pg/mL)*days | Standard Deviation 148.29 |
Secondary
Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24
Cerebral glucose metabolism was measured in validated 3 dimensional statistic surface projection analysis (Cortex ID®, GE Healthcare), transversal/coronal/sagittal-slice analysis (HERMES BRASS), and voxel-wise whole brain analysis (SPM5) using \[18F\]fluorodeoxyglucose positron emission tomography.
Time frame: Baseline to Week 24
Population: Full analysis set: All randomized participants who received at least 1 infusion of the study medication and had at least 1 post-baseline efficacy assessment. Only participants with available data were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.83 µCi/mL | Standard Deviation 0.06 |
| Placebo Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.84 µCi/mL | Standard Deviation 0.07 |
| Placebo Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.79 µCi/mL | Standard Deviation 0.05 |
| Placebo Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.80 µCi/mL | Standard Deviation 0.03 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.78 µCi/mL | Standard Deviation 0.05 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.83 µCi/mL | Standard Deviation 0.07 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.81 µCi/mL | Standard Deviation 0.06 |
| 0.1 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.77 µCi/mL | Standard Deviation 0.06 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.81 µCi/mL | Standard Deviation 0.06 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.84 µCi/mL | Standard Deviation 0.09 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.83 µCi/mL | Standard Deviation 0.06 |
| 0.25 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.80 µCi/mL | Standard Deviation 0.07 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.83 µCi/mL | Standard Deviation 0.06 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.81 µCi/mL | Standard Deviation 0.02 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.81 µCi/mL | Standard Deviation 0.05 |
| 0.4 g/kg Octagam 10% Every 2 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.80 µCi/mL | Standard Deviation 0.07 |
| Placebo Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.81 µCi/mL | Standard Deviation 0.08 |
| Placebo Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.81 µCi/mL | Standard Deviation 0.07 |
| Placebo Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.82 µCi/mL | Standard Deviation 0.07 |
| Placebo Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.81 µCi/mL | Standard Deviation 0.08 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.84 µCi/mL | Standard Deviation 0.05 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.84 µCi/mL | Standard Deviation 0.05 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.87 µCi/mL | Standard Deviation 0.04 |
| 0.2 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.88 µCi/mL | Standard Deviation 0.03 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.81 µCi/mL | Standard Deviation 0.05 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.82 µCi/mL | Standard Deviation 0.08 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.80 µCi/mL | Standard Deviation 0.06 |
| 0.5 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.84 µCi/mL | Standard Deviation 0.07 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.82 µCi/mL | Standard Deviation 0.03 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Baseline | 0.77 µCi/mL | Standard Deviation 0.04 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Left hippocampus - Week 24 (n=6,6,6,5,3,6,8,6) | 0.79 µCi/mL | Standard Deviation 0.05 |
| 0.8 g/kg Octagam 10% Every 4 Weeks | Left and Right Hippocampal Cerebral Glucose Metabolism at Baseline and at Week 24 | Right hippocampus - Baseline | 0.81 µCi/mL | Standard Deviation 0.04 |