PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF THE SAFETY AND EFFECTIVENESS OF IMMUNE GLOBULIN INTRAVENOUS (HUMAN), 10% SOLUTION (IGIV,10%) FOR THE TREATMENT OF MILD TO MODERATE ALZHEIMER'S DISEASE (AD) (Protocol #161003)
This study is of an investigational FDA approved intravenous immune globulin (IGIV) that will be studied in three treatment arms. doses of IGIV, 10% (0.2 g/kg body weight [BW] or 0.4 g/kg BW) or placebo (human albumin 0.25%) every 2 weeks, in a double-blind fashion over a period
of 71 weeks. The duration of study participation for each subject is anticipated to be approximately 18 months.
The primary outcome for this study is to evaluate the change from baseline to18 months to see if it slows the rate or prevents the progression of decline of dementia symptoms in subjects with mild-to-moderate AD as compared to placebo, as measured by ADAS-Cog and Activities of Daily Living (ADL) inventory.
The efficacy outcomes are:
1. ADCS-Clinical Global Impression of Change (CGIC) at 18 months
2. Neuropsychiatric Inventory (NPI) at 18 months
3. Logsdon Quality of Life in Alzheimer[Right Quote]s Disease (QOL-AD)
4. Impact of Alzheimer[Right Quote]s Disease on Caregiver Questionnaire (IADCQ)
5. Rate of whole brain atrophy and ventricular enlargement using volumetric MRI at 18 months
The safety outcomes are:
1. Number (percentage) of subjects experiencing related adverse events (AEs) and/or serious adverse events (SAEs)
2. Number (percentage) of subjects experiencing any AEs and/or SAEs
3. Number (percentage) of infusions temporally associated (defined as during or within 72 hours of completion of an infusion) with AEs and/or SAEs
4. Number (percentage) of infusions associated with AEs and/or SAEs occurring during or within 7 days of completion of an infusion
5. Number (percentage) of infusions causally associated with AEs and/or SAEs
6. Number and proportion of infusions discontinued, slowed, or interrupted due to an AE.
1. Healthcare Resource Utilization Questionnaire (HRUQ)
2. Time to skilled nursing facility placement
3. EuroQuol 5-Dimension (EQ-5D) health-related quality of life questionnaire (proxy version)
4. Volumetric MRI (e.g. rate of hippocampal atrophy, entorhinal cortical thickness, regional cortical thinning)
5. Cerebral glucose metabolism using FDG-PET imaging (sub-study)
This is a multicenter trial. The study population will consist of approximately 402 randomized subjects from all multi-centers. This site plans to consent 35 subjects to allow for screen failures and early withdrawals to obtain 16 participating subjects.
1. Males or females of age 50 to 89 years inclusive at the time of screening;
2. Written informed consent obtained from either the subject or the subject’s legally authorized representative prior to any study-related procedures;
3. Written informed consent obtained from an able and competent caregiver who is willing to comply with the requirements of the protocol pertaining to him/her, including facilitating the subject’s participation in the study;
4. Diagnosis of Probable AD according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDSADRDA) 1984 criteria;
5. Dementia of mild to moderate severity (MMSE 16-26 inclusive at the time of screening);
6. Neuroimaging (computed tomography [CT] or MRI) performed after symptom onset consistent with AD diagnosis;
7. Willingness to comply with the requirements of the protocol and ability to comply with testing and infusion regimen, including adequate corrected visual acuity and hearing ability;
8. For at least 12 weeks prior to screening, on stable doses of AD medication(s) approved by local regulatory authorities Subjects must not be on two acetylcholinesterase inhibitors concurrently;
9. Venous access for repeated infusion and phlebotomy;
10. If receiving psychoactive medications (e.g., antidepressants other than monoamine oxidase inhibitors [MAOIs] and most tricyclics, antipsychotics, anxiolytics, anticonvulsants, mood stabilizers, etc.), must be on stable doses for at least 6 weeks prior to screening; and
11. For women of childbearing potential, the subject must have a negative pregnancy test at screening and must agree to employ adequate contraceptive measures (e.g. birth control pills/patches, intrauterine device, or diaphragm or condom [for male partner] with spermicidal jelly or foam) throughout the course of the study.