A clinical trial of MABT5102A for the treatment of Alzheimer's Disease
- Conditions
- Alzheimer's DiseaseMedDRA version: 14.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2010-022598-32-ES
- Lead Sponsor
- Genentech Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 91
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 < 6
? CDR score of ? 0.5
? Completion of 6 years of education (or good work history consistent with
exclusion of mental retardation or other pervasive developmental disorders)
Related to Medication
? For patients currently receiving treatment with approved AD treatments
(AChE inhibitors or memantine): Treatment initiated and continued for at
least the last 3 months prior to randomization, at a stable dose for at least the
last 2 months prior to randomization
? For patients currently receiving other prescription medications that might
affect cognitive function (e.g., antidepressants, antipsychotics): Treatment at
a stable dose for ? 1 month prior to randomization
Related to Brain Amyloid Load
? Brain amyloid load in the range expected for AD patients as assessed by an
expert, blinded visual reading of the screening florbetapir-PET scan
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess amyloid burden via 18F-florbetapir (18F-AV-45) positron emission tomography<br>(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<br>? 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<br>? See protocol for more;Primary end point(s): The primary efficacy outcome measure is the change in brain amyloid load from<br>baseline to Week 69 as assessed by florbetapir-PET imaging.;Timepoint(s) of evaluation of this end point: 69 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The secondary efficacy outcome measures are as follows:<br>? Changes in CSF biomarkers relevant to AD from baseline to Week 69<br>? Change in brain metabolism from baseline to Week 69 as assessed by<br>FDG-PET imaging<br>? Change in CDR-SOB score from baseline to Week 73<br>? Change in ADAS-Cog (12-item) score from baseline to Week 73;Timepoint(s) of evaluation of this end point: 73 weeks