DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, EFFICACY AND SAFETY STUDY OF CRENEZUMAB IN PATIENTS WITH PRODROMAL- TO-MILD ALZHEIMER?S DISEASE

Punti finali primari (Fonte di dati: WHO)

Main Objective: Efficacy:evaluate crenezumab 60mg/kg compared with placebo when admin. by IVinfusion q4w over 100wks as measured by the CDR-SB(final outcome assessment at Wk 105,4 wks after final dose)Change from baseline on CDR-sum of boxes
Safety:evaluate safety of crenezumab compared with placebo in patients with prodromal to mild AD on the basis of following endpoints
?Nature,frequency,severity and timing of adverse events and serious adverse events
?Physical and neurologic examinations,vital signs,blood tests,ECGs,Columbia Suicide Severity Rating Scale,Non-serious adverse events of special interest,specific.pneumonia
?Adverse events,as assessed by magnetic resonance imaging:amyloid related imaging abnormalities edema/effusion and amyloid related imaging abnormalities hemosiderin deposition
?Immunogenic potential of crenezumab through measurement of antibodies directed against crenezumab and other components of the drug product,assessment of their relationship with other outcome measures;Secondary Objective: Efficacy: secondary efficacy objectives for this study are to evaluate the benefits of crenezumab versus placebo administered to patients by IV
infusion Q4W over 100 weeks through assessment of the following endpoints
Change from baseline to Week 105 on:
?Cognition, as assessed by the ADAS-Cog (subscale) 13 (ADAS Cog 13) and 11 (ADAS-Cog-11)
?severity of dementia, assessed using the CDR-Global Score (CDR GS) and MMSE
?function, assessed using the ADCS-ADL instrumental subscale (ADCSiADL) and ADCS-ADL total score
?neuropsychological symptoms, assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q) total score
?Effect of crenezumab on health-related quality of life (QoL), assessed using the Quality of Life-Alzheimer's Disease scale, caregiver burden, assessed using the Zarit Caregiver Interview for Alzheimer's Disease scale and on health outcomes in patient and caregiver as measured by EQ-5D
? Measure of dependence derived from the ADCS-ADL score;Primary end point(s): To evaluate crenezumab 60 mg/kg compared with placebo when administered by IV infusion q4w over 100 weeks as measured by the following primary endpoint (final outcome assessment at Week 105, 4 weeks after the final dose): Global outcomes, as assessed by the CDR SB
;Timepoint(s) of evaluation of this end point: Change from baseline at week 105