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Trial record 16 of 31 for:    alzheimer dijon

Progress of Mild Alzheimer's Disease in Participants on Solanezumab Versus Placebo (EXPEDITION 3)

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ClinicalTrials.gov Identifier: NCT01900665
Recruitment Status : Terminated (Solanezumab did not meet the study's primary endpoint.)
First Posted : July 16, 2013
Results First Posted : March 14, 2018
Last Update Posted : May 3, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

July 12, 2013
July 16, 2013
February 16, 2018
March 14, 2018
May 3, 2018
July 2013
October 2016   (Final data collection date for primary outcome measure)
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14) [ Time Frame: Baseline, Week 80 ]
The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure consists of 14 items assessing areas of cognitive function most typically impaired in AD: 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. Least Squares (LS) Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14) [ Time Frame: Baseline, Week 80 ]
  • Change from Baseline in Alzheimer's Disease Cooperative Study- Instrumental Activities of Daily Living (ADCS-iADL) [ Time Frame: Baseline, Week 80 ]
Complete list of historical versions of study NCT01900665 on ClinicalTrials.gov Archive Site
  • Change From Baseline in Alzheimer's Disease Cooperative Study- Instrumental Activities of Daily Living (ADCS-iADL) [ Time Frame: Baseline, Week 80 ]
    The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 11 Item Subscore (ADAS-Cog11) [ Time Frame: Baseline, Week 80 ]
    The cognitive subscale of ADAS (ADAS Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline, Week 80 ]
    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. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) [ Time Frame: Baseline, Week 80 ]
    The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Functional Activities Questionnaire (FAQ) [ Time Frame: Baseline, Week 80 ]
    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 financial management, shopping, playing games, food preparation, traveling, keeping appointments, keeping track of current events, and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. A negative change indicated an improvement from baseline. FAQ Total Score is the sum of 10 items, ranging from 0 (best possible outcome) to 100 (worst possible outcome). LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, Week 80 ]
    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. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline, Week 80 ]
    NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. Total score ranges from 12 to 144; Higher scores indicate greater disease severity. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) [ Time Frame: Baseline, Week 80 ]
    Assesses healthcare resource utilization (formal and informal care). Information gathered on both caregivers (care-giving time, work status) and participants (accommodation and healthcare resource utilization) was gathered from baseline and follow-up interviews. Reported number of hospitalizations per participant up to 76 weeks. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) [ Time Frame: Baseline, Week 80 ]
    Assesses QoL for AD: 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 to 52). Higher scores indicate greater QoL. Participant's primary caregiver asked to complete same measure. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in 5-Dimensional EuroQol Quality of Life Scale Proxy Version (EQ-5D Proxy) [ Time Frame: Baseline, Week 80 ]
    EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. Visual analog scale (VAS) assesses caregiver's impression of participant's health state; score ranges: 0 to 100 millimeter (mm). Lower scores=greater disease severity LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: Baseline, Week 80 ]
    Integrated Alzheimer's Disease Rating Scale is used to assess that solanezumab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of ADAS-Cog 13 or 14 and the ADCS-iADL. The scale ranges from 0 to 146, where lower scores indicate worse performance. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Percentage of Participants of Cognitive and Functional Responders [ Time Frame: Baseline through Week 80 ]
    Assess the proportion of participants who reach certain levels of cognitive and functional decline. Decline in cognition was defined as worsening from baseline by at least 6 or 9 points on the ADAS Cog14. If there is a cognitive decline of a specified cut-off or more at any time then the participant is considered a nonresponder. Functional nonresponders are participants who have not had any of the following at any time point: Clinically evident decline in ability to perform one or more basic ADL present at baseline; A clinically evident decline in ability to perform 20% or more of the instrumental ADL present at baseline; An increase in global CDR score of 1 point or more compared with baseline. A decline from no impairment to mild impairment (bADL, iADL is not considered clinically significant, but other declines of 1 or more points and any participant discontinuation within the first 6 months will be considered a non-responder.
  • Change From Baseline in Plasma Amyloid-Beta (Aβ) Species [ Time Frame: Baseline, Week 80 ]
    Concentration of amino acid peptide known as Aβ 1-42 in plasma. The change in plasma Aβ analytes after treatment were assessed separately for each plasma Aβ parameter. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 80 ]
    The vMRI assessment of right and left hippocampal atrophy, is reported. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Solanezumab (LY2062430) [ Time Frame: Visit 2 (Post-dose), Visit 5, 9, 15 (Pre-dose, Post-dose) and Visit 22 (Pre-dose): Pre-dose before the infusion, Post-dose 30 minutes End of Infusion ]
    Area Under the Concentration versus Time Curve was evaluated for Solanezumab.
  • Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan [ Time Frame: Baseline, Week 80 ]
    Florbetapir PET imaging was used to confirm the presence of amyloid pathology consistent with AD. Change from baseline was done to test the hypothesis that amyloid burden was reduced in participants in the treatment group. The change from baseline to the postbaseline visit of the composite summary standard uptake value ratio of florbetapir F18 was calculated. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit. The composite summary measure is an unweighted average of the 6 smaller regions (anterior cingulate, frontal medial orbital, parietal, posterior cingulate, precuneus, and temporal) normalized to whole cerebellum or subject-specific white matter.
  • Change From Baseline in Cerebrospinal Fluid (CSF) Aβ Levels [ Time Frame: Baseline, Week 80 ]
    Concentration of CSF parameters includes amino acid peptide known as Aβ 1-42 and Aβ 1-42. Analyses of these CSF biomarkers was conducted in a subset of participants (as an addendum to the protocol). The dependent variable for each CSF parameter was its change from baseline to endpoint. LS Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
  • Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 11 Item Subscore (ADAS-Cog11) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Mini-Mental State Examination (MMSE) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Functional Activities Questionnaire (FAQ) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in 5-Dimensional EuroQol Quality of Life Scale Proxy Version (EQ-5D Proxy) [ Time Frame: Baseline, Week 80 ]
  • Proportion of Cognitive and Functional Responders [ Time Frame: Baseline through Week 80 ]
  • Change From Baseline in Plasma Amyloid-Beta (Aβ) Species [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 80 ]
  • Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Solanezumab (LY2062430) [ Time Frame: Baseline through Week 80 ]
  • Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan [ Time Frame: Baseline, Week 80 ]
  • Change From Baseline in Cerebrospinal Fluid (CSF) Aβ Levels [ Time Frame: Baseline, Week 80 ]
Not Provided
Not Provided
 
Progress of Mild Alzheimer's Disease in Participants on Solanezumab Versus Placebo
Effect of Passive Immunization on the Progression of Mild Alzheimer's Disease: Solanezumab (LY2062430) Versus Placebo
To test the idea that solanezumab will slow the cognitive decline of Alzheimer's Disease (AD) as compared with placebo in participants with mild AD.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alzheimer's Disease
  • Drug: Solanezumab
    Administered Intravenously (IV)
    Other Names:
    • LY2062430
    • A Beta Antibody
  • Drug: Placebo
    Administered IV
  • Experimental: Solanezumab
    Solanezumab 400 milligrams (mg) every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
    Intervention: Drug: Solanezumab
  • Placebo Comparator: Placebo
    Placebo every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
    Intervention: Drug: Placebo
Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M, Hager K, Andreasen N, Scarpini E, Liu-Seifert H, Case M, Dean RA, Hake A, Sundell K, Poole Hoffmann V, Carlson C, Khanna R, Mintun M, DeMattos R, Selzler KJ, Siemers E. Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease. N Engl J Med. 2018 Jan 25;378(4):321-330. doi: 10.1056/NEJMoa1705971.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2129
2100
February 2017
October 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
  • Has a Modified Hachinski Ischemia Scale score of less than or equal to 4
  • Has a Mini-Mental State Examination (MMSE) score of 20 through 26 at Screening visit
  • Has a Geriatric Depression Scale score of less than or equal to 6 (on the staff-administered short form)
  • Has had a magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD
  • Has a florbetapir positron emission tomography (PET) scan or cerebrospinal fluid (CSF) result consistent with the presence of amyloid pathology at screening

Exclusion Criteria:

  • Does not have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week), will accompany the participant to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications
  • Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia
  • Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years
  • Has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness
  • Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen posttreatment
  • Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions
  • Has received acetylcholinesterase inhibitor (AChEIs), memantine and/or other AD therapy for less than 4 months or has less than 2 months of stable therapy on these treatments
  • Has received medications that affect the central nervous system (CNS), except treatments for AD, for less than 4 weeks
  • Has a history of chronic alcohol or drug abuse/dependence within the past 5 years
  • Has a Visit 1 MRI with results showing >4 Amyloid-related Imaging Abnormality (ARIA), -hemorrhage /hemosiderin deposition (ARIA-H) or presence of ARIA-E (edema/effusions)
Sexes Eligible for Study: All
55 Years to 90 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   France,   Germany,   Italy,   Japan,   Poland,   Spain,   Sweden,   United Kingdom,   United States
 
 
NCT01900665
15136
H8A-MC-LZAX ( Other Identifier: Eli Lilly and Company )
Yes
Not Provided
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Eli Lilly and Company
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP