mild to moderate Alzheimer´s disease
Conditions
Interventions
Trade Name: Octagam 10%
Product Name: Octagam 10%
Pharmaceutical Form: Solution for infusion
Current Sponsor code: Octagam 10%
Other descriptive name: Human polyvalent immunoglobulin
Concentration uni
Sponsors
Octapharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: · Probable AD according to NINCDS-ADRDA criteria. · Written informed consent by patient or, for significantly cognitively impaired individuals, their legally authorized representative. · Age: >=50 and =16 and = 1 hour available. · Outpatient status (includes “Betreutes Wohnen” in Germany) or assisted living in US. · 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 (e.g. 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 ECG or clinically not significant, if outside normal limits. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: · Other causes of dementia (e.g. vascular dementia, Lewy Body dementia, fronto-temporal dementia, Creutzfeld-Jacob disease, Huntington’s disease, Parkinson’s disease). · History of or present significant other diseases of the central nervous system (e.g. brain tumor, normal pressure hydrocephalus, stroke, severe brain trauma, brain surgery, epilepsy, encephalitis). · Geriatric depression scale of > 7 (short form with scale from 0 to 15). · Present significant psychiatric disorder (e.g. 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, though on stable replacement therapy for >= 3 months is acceptable. · Unstable thyroid dysfunction, stable treated hypothyroidism for >= 3 months is acceptable, but not hyperthyroidism · Uncontrolled hypertension (diastolic BP> 90 mmHg or systolic BP> 160 mmHg; sitting). · Severe liver or kidney disease (ALAT > 3x upper limit of normal, creatinine > 120 µmol/L). · Major surgery within three months prior to screening (e.g. heart surgery, hip replacement). · Prohibited medications: antiepileptic drugs, antipsychotics, antiparkinson agents, anticholinergic drugs, selegiline, MAOI, tricyclics, immunosuppressive medications, anti-histamines (unless on a stable dose for at least 3 months), benzodiazepines, and Lithium · Antidepressants are not permitted, unless if on stable dose for at least 3 months and without significant anticholinergic side-effects · Potential reasons that patient may become non-evaluable during the study (e.g. 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 (e.g. 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 other drug trial currently or within the previous 3 months before screening. · Participation in immunological treatment studies of AD other than with IGIV within the previous 6 months before screening. · IGIV use in the previous six 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 |
|---|---|
| Main Objective: The primary objective is to evaluate the decrease of Ab in the CNS and the increase in blood plasma, thereby corroborating the assumed primary mechanism of action of IGIV in AD patients, namely the interference with the pathomechanism for AD ("amyloid cascade hypothesis").;Secondary Objective: 1. To characterize the decrease of Ab in the CSF and the increase in blood plasma by measuring an add. surrogate parameter (Ab1-42), by assessing the changes in the proteins Tau and phosphorylated Tau and of the anti-Ab during the treatment period. 2. To Assess the safety of treatment with octagam® 10% in patients with mild to moderate AD, and to explore the clinical effect of monthly doses of 0.2 g/kg, 0.5 g/kg or 0.8 g/kg octagam® 10% either after 6 infusions at 4-week intervals or after 12 infusions at 2-week intervals (0.1 g/kg, 0.25 g/kg, and 0.4 g/kg) compared to baseline by assessing the results from the following psychometric tests: ADAS cog, MMSE, ADCS-ADL, CDR 3. the change in whole brain and hippocampal volume on volumetric MRI at week 24 compared to screening will be determined. In most patients (not at center of Marburg), the change in cerebral glucose metabolism will be determined by FDG-PET. ;Primary end point(s): Comparing mean AUC values of the blood plasma changes in total Ab after last infusion with IGIV or placebo from the value prior to last infusion. I.e., the value obtained from the trough level blood sample taken immediately before the last infusion will function as baseline for the AUC calculation. AUC values will be determined by four or six measurements: days 1 (to 2), 4 (±1), 7 (±1), 14 (±2) after week 22 (patients on 2-week intervals) or days 1 (to 2), 4 (±1), 7 (±1), 14 (±2), 21 (±2) and 28 (±2) after week 20 (patients on 4-week intervals), respectively. The three different IGIV dosage arms in each of the two treatment interval groups will be compared to their corresponding placebo arm. arm. | — |
Countries
Germany
Outcome results
None listed