A Study of Solanezumab (LY2062430) in Participants With Prodromal Alzheimer's Disease

Phase 3TerminatedNCT02760602

Eli Lilly and Company26 enrolled

Overview

The main purpose of this study is to investigate the safety and efficacy of the study drug solanezumab in participants with prodromal Alzheimer's disease (AD).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Alzheimer's Disease

Interventions

SolanezumabDRUG

Administered IV

PlaceboDRUG

Administered IV

Eligibility

Sex: ALLMin age: 55 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has a diagnosis by the study investigator of a clinical syndrome of cognitive impairment consistent with prodromal AD per International Working Group (IWG) diagnostic criteria or mild cognitive impairment (MCI) due to AD per National Institute on Aging-Alzheimer's Association (NIA-AA) diagnostic criteria. * Scores 17-28 on Montreal Cognitive Assessment (MoCA) at screening. * Scores \<27 on free recall cutoff score from the Free and Cued Selective Reminding Test (FCSRT) (Picture version) at screening. * Scores ≤4 on Modified Hachinski Ischemia Scale (MHIS). * Scores \>0 on the Functional Activities Questionnaire (FAQ). * Has a florbetapir positron emission tomography (PET) scan or cerebrospinal fluid (CSF) result at screening consistent with the presence of amyloid pathology. Exclusion Criteria: * Has had MRI or computerized tomography (CT) of brain within previous 2 years showing pathology that would be inconsistent with a diagnosis of AD. * Has known allergy to humanized monoclonal antibodies. * Has an ongoing clinically significant laboratory abnormality, as determined by the investigator. * Has screening MRI with results showing \>4 amyloid related imaging abnormalities H (ARIA-H) micro-hemorrhages or presence of ARIA-E. * Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI. * Has received treatment with a stable dose of an acetylcholinesterase (AChEI) inhibitor or memantine for less than 2 months before randomization. (If a participant has recently stopped AChEIs and/or memantine, he or she must have discontinued treatment at least 2 months before randomization.)

Locations (193)

Outcomes

Primary Outcomes

Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog14) Score

ADAS-Cog14 is ADAS-Cog11 augmented with orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze-completion measures. The ADAS-Cog14 scale ranges from 0 to 90. Higher scores indicate greater disease severity.

Time frame: Baseline, 24 Months

Secondary Outcomes

Change From Baseline on Alzheimer´s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL)

The ADCS-MCI-ADL is a functional evaluation scale for MCI patients, based on information provided by an informant that describes the performance of participants in several ADLs. Total score ranges from 0 to 69; lower score indicates greater disease severity.

Time frame: Baseline, 24 Months

Change From Baseline on the Mini Mental Status Examination (MMSE)

MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants.Total score ranges from 0 to 30; lower score indicates greater disease severity.

Time frame: Baseline, 24 Months

Change From Baseline on the Montreal Cognitive Assessment (MoCA)

The MoCA will be used as the global cognitive screening instrument. It will also be administered in the clinical trial at baseline and the final visits of each phase as a secondary outcome measure of global cognition. Scores on the MoCA range from 0-30 with 26-30 indicating normal global cognition.

Time frame: Baseline, 24 Months

Change From Baseline on the Functional Activities Questionnaire (FAQ)

FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from Writing checks, Assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, Traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now = 1; Never did \[the activity\] but could do now = 0; Normal = 0; Has difficulty but does by self = 1; Requires assistance = 2; Dependent = 3). The maximum FAQ total score is 30, with higher scores indicating greater impairment.

Data from ClinicalTrials.gov

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Xenoscience

Phoenix, Arizona, United States

Banner Alzheimer's Institute

Phoenix, Arizona, United States

St Josephs Hospital and Medical Center

Phoenix, Arizona, United States

Banner Sun Health Research Institute

Sun City, Arizona, United States

Center for Neurosciences

Tucson, Arizona, United States

Arizona Health Sciences Center

Tucson, Arizona, United States

Parexel Early Phase Unit at Glendale

Glendale, California, United States

Pacific Neuroscience Medical Group

Oxnard, California, United States

Desert Valley Research

Rancho Mirage, California, United States

Pacific Research Network Inc

San Diego, California, United States

...and 183 more locations

Time frame: Baseline, 24 Months

Change From Baseline on the Neuropsychiatric Inventory (NPI)

The NPI is a tool for assessing psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. The score ranges from 12 to 144, with higher scores indicating greater disease severity.

Time frame: Baseline, 24 Months

Change From Baseline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)

CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity.

Time frame: Baseline, 24 Months

Change From Baseline on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

RBANS is a brief neurocognitive battery with four alternate forms, measuring immediate and delayed memory, attention, language, and visuospatial/constructional skills.

Time frame: Baseline, 24 Months

Change From Baseline on the Free and Cued Selective Reminding Test (FCSRT)

The FCSRT is a neuropsychological test of memory under conditions that control attention and cognitive processing in order to obtain an assessment of memory unconfounded by normal age-related changes in cognition.

Time frame: Baseline, 24 Months

Change From Baseline on the Resource Utilization in Dementia-Lite (RUD-Lite)

RUD-Lite assesses the healthcare resource utilization of participants and their caregivers to determine the level of formal and informal care attributable to Alzheimer's Disease (AD). Information on both caregivers (caregiving time, work status) and participants (accommodation and healthcare resource utilization) is collected from the baseline and follow-up interviews.

Time frame: Baseline, 24 Months

Change From Baseline on the EuroQol 5-Dimensional Health-Related Quality of Life Scale (EQ-5D)

EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Visual analogue scale (VAS) assesses caregiver's impression of participant's overall health state; scores range: 0 to 100. Lower scores indicate greater disease severity.

Time frame: Baseline, 24 Months

Change From Baseline on the Quality of Life in Alzheimer's Disease Scale (QoL-AD)

QoL for AD assess participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items rated on a 4-point scale. Sum of items=total score (range: 13-52). Higher scores=greater QoL.

Time frame: Baseline, 24 Months

Change From Baseline in Concentration of Plasma Amyloid-β Peptide (Aβ) and Plasma Solanezumab

Concentration of amino acid peptide known as Aβ 1-42 in plasma.

Time frame: Baseline, 24 Months

Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI)

MRI will be used to assess the effect of treatment on rate of whole brain volume.

Time frame: Baseline, 24 Months

Change From Baseline in Florbetapir Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVr)

Florbetapir F18 PET used to assess the treatment effect in brain amyloid plaque deposition from baseline through 18 months as measured by florbetapir F18 PET Standardized Uptake Uptake Value ratio.

Time frame: Baseline, 24 Months

Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Aβ and CSF Tau Proteins

Changes in CSF parameters, including total and free Aβ1-40 and Aβ1-42 species and total tau and P-tau181 peptides, will be assessed.

Time frame: Baseline, 24 Months

Change From Baseline in Neocortical Tau Deposits Using 18F-AV-1451 PET

Biomarker change will be analyzed to provide biomarker-based evidence that solanezumab affects the underlying disease pathology.

Time frame: Baseline, 24 Months