Alzheimer's Disease MedDRA version: 14.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: MABT5102A
Product Code: MABT5102A
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not applicable
CAS Number: 1095207-05-8
Current Sponsor code: MABT5102A
Sponsors
Genentech Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General ? Ability to provide written informed consent by the patient ? Ability and willingness of patient to comply with the protocol?s requirements ? Age 50?80 years ? Body weight ? 45 kg and ? 120 kg ? Adequate visual and auditory acuity in the investigator's judgment to allow for neuropsychological testing ? Fluent in the language of the test assessments ? For female patients, a negative serum ??human chorionic gonadotropin (?-hCG) pregnancy test at screening ? Normal thyroid-stimulating hormone (TSH) level and vitamin B12 level of ? 200 pg/mL at screening ? For male patients with partners with reproductive potential, agreement to use a reliable means of contraception (e.g., condoms) during the study ? Availability of a person ("caregiver") who can provide information on activities of daily living and behavior in order to complete the study-specific assessments This caregiver must have sufficient cognitive capacity, in the judgment of the investigator, to accurately report upon the patient's function and behavior. In addition, the caregiver must spend sufficient time with the patient to be familiar with the overall function and behavior of the patient. As guidance, a caregiver would ordinarily need to spend an average of at least 8 hours per week with the patient in order for the caregiver to meet the requirements for this study. Related to Neurology/Cognition ? Diagnosis of probable AD according to the NINCDS-ADRDA criteria (McKhann et al. 1984) ? MMSE score of 18?26 points at screening (Folstein et al. 1975) ? ADAS-Cog Delayed Word Recall score of ? 5 (i.e., ? 5 errors) ? GDS-15 score of =65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: General ? Lack of peripheral venous access ? Inability to tolerate MRI or lumbar puncture procedures or contraindication to MRI, including but not limited to pacemakers; implantable cardioverter defibrillators; cochlear implants; cerebral aneurysm clips; implanted infusion pumps; implanted nerve stimulators; metallic splinters in the eye; other magnetic, electronic, or mechanical implants; or any other clinical history or examination finding that, in the judgment of the investigator, would pose a potential hazard in combination with MRI ? Female patient with reproductive potential Female patients must either have undergone documented surgical sterilization or have not experienced menstruation for at least 12 consecutive months. ? Severe or unstable medical condition that, in the opinion of the investigator or Sponsor, would interfere with the patient's ability to complete the study assessments or would require the equivalent of institutional or hospital care Related to PET Imaging ? Inability to tolerate PET procedure ? Abnormal findings that, in the opinion of the investigator, may affect his or her response to the radiopharmaceutical and related testing procedures Related to Medical History/Conditions ? History or presence of clinically evident vascular disease potentially affecting the brain (e.g., stroke, clinically significant carotid or vertebral stenosis or plaque, aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous malformation) ? History of severe, clinically significant (persistent neurologic deficit or structural brain damage) central nervous system trauma (e.g., cerebral contusion) ? History or presence of intracranial tumor (e.g., meningioma, glioma) ? Presence of infections that affect the brain function or history of infections that resulted in neurologic sequelae (e.g., syphilis, neuroborreliosis, viral or bacterial meningitis/encephalitis, HIV encephalopathy) ? History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., multiple sclerosis, lupus erythematosus, anti-phospholipid antibody syndrome, Behçet disease) ? History or presence of psychiatric disease other than AD that may affect cognition, including but not limited to clinically significant major psychiatric disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) (e.g. major depression, schizophrenia, bipolar disorder) A history of major depression is acceptable if no episode has been reported within the previous 5 years. ? History or presence of a neurologic disease other than AD that may affect cognition, including but not limited to Parkinson?s disease, corticobasal degeneration, dementia with Lewy bodies, Creutzfeldt?Jakob disease, progressive supranuclear palsy, frontotemporal degeneration, Huntington?s disease, normal pressure hydrocephalus, and hypoxia ? History of seizures with the exception of childhood febrile seizures ? History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins ? Positive urine test for drugs of abuse at screening or known or suspected history of alcohol or drug abuse within the previous 5 years (DSM-IV criteria) Medical marijuana is not allowed and must be discontinued 3 months prior to randomization. The intermittent use of benzodiazepines is allowed, except within 2 days prior to any neurocognitive assessment. ? Evidence of mal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess amyloid burden via 18F-florbetapir (18F-AV-45) positron emission tomography (florbetapir-PET) in patients with mild to moderate AD and to evaluate whether treatment with MABT5102A (a monoclonal antibody to ?-amyloid [Abeta]) over 68 weeks results in a change in amyloid burden after dosing;Secondary Objective: ? To evaluate other potential biomarkers (e.g., CSF Abeta, CSF total tau, CSF phospho-tau-181) of safety, efficacy, and risk of disease progression in response to MABT5102A treatment ? To assess brain metabolism via 18F-fluorodeoxyglucose (FDG)?PET in patients with mild to moderate AD and to evaluate whether treatment with MABT5102A over 68 weeks results in a change in FDG-PET uptake compared with placebo ? See protocol for more;Primary end point(s): The primary efficacy outcome measure is the change in brain amyloid load from baseline to Week 69 as assessed by florbetapir-PET imaging.;Timepoint(s) of evaluation of this end point: 69 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy outcome measures are as follows: ? Changes in CSF biomarkers relevant to AD from baseline to Week 69 ? Change in brain metabolism from baseline to Week 69 as assessed by FDG-PET imaging ? Change in CDR-SOB score from baseline to Week 73 ? Change in ADAS-Cog (12-item) score from baseline to Week 73;Timepoint(s) of evaluation of this end point: 73 weeks | — |
Countries
France, Spain, United States
Contacts
Public ContactDermot Curtin
Quintiles
Outcome results
None listed