Effect of Passive Immunization on the Progression of Mild Alzheimer[Single Quote]s Disease: Solanezumab (LY2062430) Versus Placebo
The primary objective of this study is to test the hypothesis that solanezumab, administered as an intravenous infusion at a dose of 400 mg every 4 weeks for 76 weeks, will slow the cognitive and functional decline of alzheimer's disease (aD) as compared with placebo in patients with mild aD.
Solanezumab 400 mg will be administered once every 4 weeks by intravenous infusion. Study medication will be given every 4 weeks through Week 76, with final evaluations occurring 4 weeks later at Week 80, such that total duration is approximately 18 months. Placebo will be administered as an intravenous infusion of approximately 70 mL over approximately 30 minutes once every 4 weeks.
all analyses will follow the intent-to-treat (iTT) principle unless otherwise specified.
When change from baseline is assessed, subjects will be included in the analysis only if both a baseline and a
postbaseline measure are available. The co-primary endpoints of this study, aDaS-Cog14 and aDCS-iaDL, will be analyzed. The change from baseline score at each scheduled visit postbaseline (according to the Study
Schedule) during the treatment period will be the dependent variable. The null hypothesis is that the contrast
between the solanezumab group versus placebo at the last visit equals zero. a rejection of the null hypothesis in
favor of the alternative, showing that solanezumab is superior to placebo, will demonstrate a treatment effect.
an interim analysis may be conducted by the data monitoring committee (DMC) after the first
two-thirds of the randomized patients have had the opportunity to complete the study. The purpose of the interim
analysis is to potentially stop the study early for positive efficacy. in the case of early stopping, all ongoing
patients will have the option to be enrolled into an open-label extension study. Lilly may decide not to conduct the interim analysis.
in addition participants will be asked to enroll in a substudy to evaluate the level of a number of different clinical chemistry measurements related to alzheimer's disease progression, which are found in the cerebrospinal fluid (CSFxfluid surrounding the brain and spinal cord). Lumbar punctures (LPs) will be used to collect cerebrospinal fluid (CSF) for assays of CSF glucose, protein, and cell count with differential; solanezumab, albumin, amyloid beta species, and tau proteins CSF storage.
Biochemical effects of solanezumab and placebo treatments will be compared in CSF obtained from those
patients undergoing LP at Visit 2 and at endpoint (Visit 22 or at early discontinuation [eD]).
The hypothesis that solanezumab, unlike placebo, alters amyloid-plaque associated forms of a[MiCRo-SYMBoL]
will be assessed by confirming that concentrations of CSF free (unbound to antibody) a [and] #946;1-42
are increased or unchanged, and CSF-free a[MiCRo-SYMBoL]1-40 levels are decreased with solanezumab
treatment. The hypothesis that solanezumab reduces or slows the rise in the concentration of tau proteins in CSF compared with placebo will be assessed by measuring treatment effects on concentrations of CSF tau proteins.
Results of the LP performed under this addendum will not affect the continued participation of
patients in the study that underwent florbetapir positron emission tomography (PeT) imaging at
baseline if the LP results do not agree with the PeT data as evidence of aD pathology.
on the last main study visit subjects will be asked to further participate in the open Label extension of the Lumbar Puncture Protocol addendum. Please note that there are 2 optional consent forms to be signed once the parent study has ended. one optional consent form is for the open Label extension part of the study (mod 9) and the second optional consent form is for the Lumbar Puncture addendum for the open Label extension study.
Subjects will continue with the aDaS-Cog assessments at wk25-48, sponsor requires forms with footer to differentiate between core study and open label.
Patients are eligible to be included in the study only if they meet all of the following criteria:
 Meets National Institute of Neurological and Communicative Disorders and
Stroke/Alzheimer[Single Quote]s Disease and Related Disorders Association
criteria for probable AD as determined by a neurologist, psychiatrist, or
clinician approved by the Sponsor or designee.
 Has a Modified Hachinski Ischemia Scale score of <=4.
 Has an MMSE score of 20 through 26 at Visit 1
 Has a Geriatric Depression Scale score of <=6
 Has had an MRI or computerized tomography (CT) scan performed within the
past 2 years that has confirmed no findings inconsistent with a diagnosis of
AD. If a patient has not had a prestudy MRI/CT scan in the past 2 years or attempts to obtain offsite imaging results are unsuccessful, then the MRI scan required at Visit 1
(screening) may be used to assess eligibility upon approval by the Global
 Male or female patients ages 55 to 90 years old. Females of childbearing
potential must test negative for pregnancy at Visit 1 based on a serum
pregnancy test and use medically accepted means of contraception.
 If receiving concurrent treatment with an AChEI and/or memantine, has been
on the medication for at least 4 months with a stable dose for at least 2 months
before Visit 2. Dosing is to remain stable throughout the study
 Has a florbetapir PET scan or CSF result consistent with the presence of
amyloid pathology at screening.