E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
mild to moderate Alzheimer´s disease |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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"). |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 <=85. · MMSE: >=16 and <=26. · Only for Germany: The patient’s capacity to consent has to be confirmed by dated signature on the informed consent form by a second independent investigator who is otherwise not involved in study GAM10-04 prior to any study-related examinations. · Sufficient language skills for testing. · Sufficient vision and hearing for testing. · Modified Hachinski-Rosen Score < 5. · MRI of the head consistent with the diagnosis of AD · Caregiver with contact at least 4 days per week for >= 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the last visit of the last patient undergoing the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |