Mild to moderate Alzheimer’s disease (AD) MedDRA version: 14.1 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 100000004852
Conditions
Interventions
Trade Name: KIOVIG 100 mg/ml solution for infusion
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Human normal immunoglobulin
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN
Conce
Sponsors
Baxter Innovations GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 (NINCDS-ADRDA) 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. 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. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 302
Exclusion criteria
Exclusion criteria: 1.Possible AD by NINCDS-ADRDA criteria or non-Alzheimer dementia (e.g. vascular dementia, dementia with Lewy bodies, frontotemporal dementia, or dementia arising from other diseases or conditions such as Parkinson’s disease, vit. B12 deficiency, thyroid abnormalities). 2.Current residence in a skilled nursing facility. 3.Contraindication to undergoing MRI (e.g. pacemaker [with the exception of an MRI-compatible pacemaker], severe claustrophobia, ferromagnetic implants such as a metal plate). 4.Clinically signif. congestive heart failure (e.g. New York Heart Association [NYHA] Class III/IV symptoms or untreated Class II). 5.History of unstable angina (angina at rest) or myocardial infarction within the 12 months prior to screening. 6.Uncontr. hypertension defined as syst. blood pressure >160mmHg and/or diast. >100mmHg confirmed upon repeated measures. 7.History of thrombosis and/or thromboembolic disease (central or peripheral) within the 12 months prior to screening. 8.Known history of procoagulant abnormalities (e.g. factor V Leiden, antiphospholipid syndr., protein S/protein C deficiency, AT III deficiency). 9.History of intracerebral hemorrhage within the 5 yrs prior to screening. 10.Evidence of >4 microhemorrhages (regardless of their anatom. location or diag. characterization as “possible” or “definite”), a single area of superficial siderosis, a macrohemorrhage, major stroke, or multiple lacunae by a recent (within 3 months prior to screening) and/or the baseline MRI, as confirmed by an indep. qualified central reviewer. 11.Head trauma with loss of consciousness, contusion, or open head injury within the 12 months prior to screening. 12.Uncontr. seizure disorder as defined by =2 breakthrough seizures/year despite adequate antiepileptic drug (AED) treatment. 13.Modified Hachinski score >4 at time of screening. 14.Subjects with active malignancy or history of malignancy within 5 yrs prior to screening with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix & stable prostate cancer not requiring treatment. 15.Active autoimmune/neuro-immunologic disorder. 16.Uncontr. major depression, psychosis, or other major psych. disorder(s). 17.Poorly contr. diabetes, defined as glycosylated (or glycated) hemoglobin (HbA1c) =6.5% at screening. 18.Creatinine clearance 2.5 x upper limit of normal (ULN) b.Clinically signif. anemia that precludes repeated blood sampling or hemoglobin (Hgb) 9 g/dL 21.Known history of/positive serology at screening for one/more of the following: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) type 1/2 antibody. 22.Immunoglobulin A (IgA) deficiency (<8 mg/dL). 23.Known history of hypersensitivity following infusions of human blood/blood components (e.g. human Ig or human albumin). 24.Currently receivi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of IGIV, 10% treatment on change in cognitive performance and functional activities in subjects with mild to moderate AD, as compared to placebo.;Secondary Objective: 1.To evaluate the effects of IGIV, 10% treatment on additional outcomes, including global clinical status, neuropsychiatric behaviors, and changes in volumetric magnetic resonance imaging (MRI) parameters. 2.To examine the effects of IGIV, 10% treatment on quality of life of subjects with mild to moderate AD and of their caregivers. 3.To assess the safety of IGIV, 10% treatment in subjects with mild to moderate AD. ;Primary end point(s): 1.The cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-Cog) 2.Alzheimer’s Disease Cooperative Study (ADCS)-Activities of Daily Living (ADL) inventory;Timepoint(s) of evaluation of this end point: 1. ADAS-Cog: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable) 2. ADCS-ADL: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy 1.ADCS-Clinical Global Impression of Change (CGIC) 2.Neuropsychiatric Inventory (NPI) 3.Logsdon Quality of Life in Alzheimer’s Disease (QOL-AD) 4.Impact of Alzheimer’s Disease on Caregiver Questionnaire (IADCQ) 5.Rate of whole brain atrophy and ventricular enlargement using volumetric MRI Safety 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 ;Timepoint(s) of evaluation of this end point: 1. ADCS-CGIC: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable) 2. NPI: Baseline, 3 months, 6 months, 9 months, 12 months, 15 months and 18 months (as well as at the early termination visit if applicable) 3. QOL-AD: Baseline, 6 months, 9 months, 12 months and 18 months (as well as at the early termination visit if applicable) 4. IADCQ: Baseline, 6 months, 9 months, 12 months and 18 months (as well as at the early termination visit if applicable) 5. Rate of whole brain atrophy and ventricular enlargement: Baseline, 9 months and 18 months | — |
Countries
Australia, Belgium, Canada, Germany, Israel, Japan, Poland, Spain, United Kingdom, United States
Contacts
Public ContactGuido Wuerth, MD
Baxter Innovations GmbH
Outcome results
None listed