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

Phase 3
Terminated
Conditions
Alzheimer's Disease
Interventions
Drug: Placebo
Registration Number
NCT02760602
Lead Sponsor
Eli Lilly and Company
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
26
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.)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo given IV once every 4 weeks for up to 2 years.
SolanezumabSolanezumabSolanezumab given intravenously (IV) once every 4 weeks for up to 2 years.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog14) ScoreBaseline, 24 Months

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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline on the Mini Mental Status Examination (MMSE)Baseline, 24 Months

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.

Change From Baseline on the Neuropsychiatric Inventory (NPI)Baseline, 24 Months

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.

Change From Baseline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)Baseline, 24 Months

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.

Change From Baseline on the Free and Cued Selective Reminding Test (FCSRT)Baseline, 24 Months

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.

Change From Baseline on Alzheimer´s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL)Baseline, 24 Months

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.

Change From Baseline on the Montreal Cognitive Assessment (MoCA)Baseline, 24 Months

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.

Change From Baseline on the Functional Activities Questionnaire (FAQ)Baseline, 24 Months

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.

Change From Baseline on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)Baseline, 24 Months

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

Change From Baseline on the Resource Utilization in Dementia-Lite (RUD-Lite)Baseline, 24 Months

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.

Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI)Baseline, 24 Months

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

Change From Baseline on the EuroQol 5-Dimensional Health-Related Quality of Life Scale (EQ-5D)Baseline, 24 Months

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.

Change From Baseline in Florbetapir Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVr)Baseline, 24 Months

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.

Change From Baseline on the Quality of Life in Alzheimer's Disease Scale (QoL-AD)Baseline, 24 Months

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.

Change From Baseline in Concentration of Plasma Amyloid-β Peptide (Aβ) and Plasma SolanezumabBaseline, 24 Months

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

Change From Baseline in Neocortical Tau Deposits Using 18F-AV-1451 PETBaseline, 24 Months

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

Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Aβ and CSF Tau ProteinsBaseline, 24 Months

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

Trial Locations

Locations (103)

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

Care Access Research LLC

🇺🇸

Santa Clarita, California, United States

California Neuroscience Research

🇺🇸

Sherman Oaks, California, United States

MCB Clinical Research Centers

🇺🇸

Colorado Springs, Colorado, United States

Christiana Care Research Institute

🇺🇸

Newark, Delaware, United States

Clinical Neuroscience Solutions Inc

🇺🇸

Jacksonville, Florida, United States

Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

Suncoast Clinical Research

🇺🇸

New Port Richey, Florida, United States

Sensible Healthcare

🇺🇸

Ocoee, Florida, United States

Pensacola Research Consultants, Inc.

🇺🇸

Pensacola, Florida, United States

Quantum Laboratories

🇺🇸

Pompano Beach, Florida, United States

United Osteoporosis Center

🇺🇸

Gainesville, Georgia, United States

Alexian Brothers Medical Center

🇺🇸

Elk Grove Village, Illinois, United States

Christie Clinic, LLC

🇺🇸

Champaign, Illinois, United States

Central DuPage Hospital

🇺🇸

Winfield, Illinois, United States

Maine Neurology

🇺🇸

Scarborough, Maine, United States

Heartland Research Associates

🇺🇸

Wichita, Kansas, United States

Baptist Health Medical Group

🇺🇸

Lexington, Kentucky, United States

Lake Charles Clinical Trials

🇺🇸

Lake Charles, Louisiana, United States

ActivMed Practices & Research, Inc

🇺🇸

Portsmouth, New Hampshire, United States

Donald S Marks

🇺🇸

Plymouth, Massachusetts, United States

QUEST Research Institute

🇺🇸

Farmington Hills, Michigan, United States

Clinical Research Professionals

🇺🇸

Chesterfield, Missouri, United States

Millenium Psychiatric Associates LLC

🇺🇸

Creve Coeur, Missouri, United States

Advanced Memory Research Institute of New Jersey

🇺🇸

Toms River, New Jersey, United States

Pyramid Clinical Research

🇺🇸

Monroe, New Jersey, United States

Princeton Medical Institute

🇺🇸

Princeton, New Jersey, United States

Healthy Perspectives Innovative Mental Health Services, PL

🇺🇸

Nashua, New Hampshire, United States

The Cognitive and Research Center of NJ

🇺🇸

Springfield, New Jersey, United States

Bio Behavioral Health

🇺🇸

Toms River, New Jersey, United States

Alzheimer's Memory Center

🇺🇸

Charlotte, North Carolina, United States

Neurology Diagnostics, Inc.

🇺🇸

Dayton, Ohio, United States

Insight Clinical Trials

🇺🇸

Shaker Heights, Ohio, United States

Abington Neurological Associates

🇺🇸

Abington, Pennsylvania, United States

Clinical Trial Center, LLC, Psychiatry

🇺🇸

Jenkintown, Pennsylvania, United States

Northeastern Pennsylvania Memory & Alzheimer's Center

🇺🇸

Plains, Pennsylvania, United States

Butler Hospital

🇺🇸

Providence, Rhode Island, United States

Rhode Island Mood & Memory Research Institute

🇺🇸

East Providence, Rhode Island, United States

Metrolina Neurological Research Institute

🇺🇸

Indian Land, South Carolina, United States

Evergreen Professional Plaza

🇺🇸

Kirkland, Washington, United States

Dean Foundation for Health Research and Education

🇺🇸

Middleton, Wisconsin, United States

National Clinical Research - Richmond

🇺🇸

Richmond, Virginia, United States

Sentara Medical Group

🇺🇸

Norfolk, Virginia, United States

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

🇨🇦

Toronto, Canada

Santa Cruz Behavioral PSC

🇵🇷

Bayamón, Puerto Rico

Cortex, PSC

🇵🇷

Las Piedras, Puerto Rico

University Of Puerto Rico

🇵🇷

Rio Piedras, Puerto Rico

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

🇬🇧

Scotland, United Kingdom

Instituto de Neurologia Dra. Ivonne Fraga

🇵🇷

San Juan, Puerto Rico

Latin Clinical Trial Center

🇵🇷

San Juan, Puerto Rico

SomniCare Sleep Institute

🇵🇷

San Juan, Puerto Rico

Desert Valley Research

🇺🇸

Rancho Mirage, California, United States

Apex Research Institute

🇺🇸

Santa Ana, California, United States

Care Access Research

🇺🇸

Valencia, California, United States

New England Institute for Clinical Research

🇺🇸

Stamford, Connecticut, United States

Brain Matters Research

🇺🇸

Delray Beach, Florida, United States

Neuropsychiatric Research Center of Southwest Florida

🇺🇸

Fort Myers, Florida, United States

Sunrise Clinical Research

🇺🇸

Hollywood, Florida, United States

Roskamp Institute

🇺🇸

Sarasota, Florida, United States

Premiere Research Institute at Palm Beach Neurology

🇺🇸

West Palm Beach, Florida, United States

Atlanta Center of Medical Research

🇺🇸

Atlanta, Georgia, United States

Fort Wayne Neurological Center

🇺🇸

Fort Wayne, Indiana, United States

Johns Hopkins University School of Medicine

🇺🇸

Baltimore, Maryland, United States

PharmaSite Research Inc

🇺🇸

Baltimore, Maryland, United States

Hattiesburg Clinic

🇺🇸

Hattiesburg, Mississippi, United States

ClinVest

🇺🇸

Bolivar, Missouri, United States

Albany Medical College

🇺🇸

Albany, New York, United States

Richmond Behavorial Associates

🇺🇸

Staten Island, New York, United States

Lehigh Valley Hospital

🇺🇸

Allentown, Pennsylvania, United States

Baylor AT&T Memory Center

🇺🇸

Dallas, Texas, United States

Lehigh Center for Clinical Research

🇺🇸

Allentown, Pennsylvania, United States

FutureSearch Trials

🇺🇸

Dallas, Texas, United States

The Memory Clinic

🇺🇸

Bennington, Vermont, United States

Cotton O'Neil Clinic

🇺🇸

Topeka, Kansas, United States

Xenoscience

🇺🇸

Phoenix, Arizona, United States

Banner Alzheimer's Institute

🇺🇸

Phoenix, Arizona, United States

California Pacific Medical Center

🇺🇸

San Francisco, California, United States

St Josephs Hospital and Medical Center

🇺🇸

Phoenix, Arizona, United States

Pacific Research Network Inc

🇺🇸

San Diego, California, United States

Sharp Mesa Vista Hospital

🇺🇸

San Diego, California, United States

Miami Jewish Health Systems

🇺🇸

Miami, Florida, United States

Indiana University School of Medicine

🇺🇸

Indianapolis, Indiana, United States

Josephson Wallack Munshower Neurology

🇺🇸

Indianapolis, Indiana, United States

University of Cincinnati Medical Center

🇺🇸

Cincinnati, Ohio, United States

Houston Methodist

🇺🇸

Houston, Texas, United States

University of Texas Health Services Center - Houston

🇺🇸

Houston, Texas, United States

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

Univ of Texas Health Science Center at San Antonio

🇺🇸

San Antonio, Texas, United States

Summit Research Network Inc

🇺🇸

Portland, Oregon, United States

Mile High Research Center

🇺🇸

Denver, Colorado, United States

Center for Cognitive Health

🇺🇸

Portland, Oregon, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

Compass Research

🇺🇸

Orlando, Florida, United States

Axiom Research

🇺🇸

Tampa, Florida, United States

St Lukes Hospital

🇺🇸

Kansas City, Missouri, United States

Piedmont Medical Research

🇺🇸

Winston-Salem, North Carolina, United States

Sheppard Pratt Health System

🇺🇸

Baltimore, Maryland, United States

Las Vegas Medical Research

🇺🇸

Las Vegas, Nevada, United States

Memory Enhancement Center of America, Inc.

🇺🇸

Eatontown, New Jersey, United States

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