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ELND005 in Patients With Mild to Moderate Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00568776
Recruitment Status : Completed
First Posted : December 6, 2007
Results First Posted : March 29, 2012
Last Update Posted : May 16, 2016
Sponsor:
Collaborator:
Transition Therapeutics
Information provided by (Responsible Party):
Transition Therapeutics Ireland Limited

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Drug: Placebo Control
Drug: ELND005

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Participant Flow:   Overall Study
    Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID
STARTED   83 [1]   88 [2]   89 [3]   91 [4] 
COMPLETED   53   52   15   19 
NOT COMPLETED   30   36   74   72 
Adverse Event                8                8                10                8 
Death                0                1                4                3 
Physician Decision                0                2                0                0 
Lack of Efficacy                2                2                2                4 
Lost to Follow-up                1                1                1                1 
Protocol Violation                1                0                1                1 
Withdrawal by Subject                13                15                13                7 
Loss of Caregiver                0                2                1                2 
Sponsor Decision                2                2                41                42 
Miscellaeneous                3                3                1                4 
[1] One randomized patient withdrew consent and did not receive placebo
[2] One randomized patient withdrew consent and did not receive ELND005 250 mg BID
[3] 41 patients withdrawn per interim safety review (sponsors decision); excluded in efficacy analysis.
[4] 42 patients withdrawn per interim safety review (sponsors decision); excluded in efficacy analysis.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks
Total Total of all reporting groups

Baseline Measures
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 83   88   89   91   351 
Age 
[Units: Years]
Mean (Standard Deviation) 		 73.4  (7.83)   73.4  (7.26)   73.4  (7.56)   72.2  (8.20)   73.1  (7.7) 
Gender 
[Units: Patients]
 		         
Female   47   51   48   51   197 
Male   36   37   41   40   154 
Region of Enrollment 
[Units: Patients]
 		         
United States   68   75   71   75   289 
Canada   15   13   18   16   62 


  Outcome Measures

1.  Primary:   Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Primary
Measure Title Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS)
Measure Description The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and completed the baseline visit and at least one post-baseline visit.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 82   84   0   0 
Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -0.383  (0.075)   -0.350  (0.074)       


Statistical Analysis 1 for Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Full Analysis Set; FAS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.71
Mean Difference (Final Values) [5] 0.03
95% Confidence Interval -0.14 to 0.21
Standard Error of the mean (0.09)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



2.  Primary:   Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Primary
Measure Title Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS)
Measure Description The NTB assessment is comprised of 9 instruments that measure cognition and executive function. Three of these tests measure immediate memory, next three measure delayed memory, and remaining three assess executive function. The total score is a weighted mean of the nine tests, referred to as the Z-score. Typically, scores range from -3 and 3, with lower scores suggesting greater cognitive impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Set (PPS): all randomized patients who received at least one dose of ELND005 250 mg or placebo, completed all scheduled visits up to Week 78, were at least 80% compliant with study drug, and met all inclusion/exclusion criteria.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 47   49   0   0 
Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -0.369  (0.093)   -0.222  (0.095)       


Statistical Analysis 1 for Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Neuropsychological Test Battery (NTB) Z-score (Per Protocol Set; PPS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.17
Mean Difference (Final Values) [5] 0.15
95% Confidence Interval -0.06 to 0.36
Standard Error of the mean (0.11)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



3.  Primary:   Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Primary
Measure Title Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS)
Measure Description The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and completed the baseline visit and at least one post-baseline visit.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 82   84   0   0 
Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -9.467  (1.641)   -10.861  (1.604)       


Statistical Analysis 1 for Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Full Analysis Set; FAS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.49
Mean Difference (Final Values) [5] -1.39
95% Confidence Interval -5.41 to 2.62
Standard Error of the mean (2.03)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



4.  Primary:   Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Per Protocol Set; PPS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Primary
Measure Title Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Per Protocol Set; PPS)
Measure Description The ADCS-ADL is a 23-item scale that measures a subject's functional abilities as assessed by the subject's caregiver. This scale ranges from 0 to 78, with lower scores suggesting greater functional impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Set (PPS): all randomized patients who received at least one dose of ELND005 250 mg or placebo, completed all scheduled visits up to Week 78, were at least 80% compliant with study drug, and met all inclusion/exclusion criteria.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 47   49   0   0 
Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Per Protocol Set; PPS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -9.635  (1.779)   -8.987  (1.760)       


Statistical Analysis 1 for Additional Analysis of Primary Outcome Measure: Change From Baseline to Week 78 in Alzheimer‘s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) Score (Per Protocol Set; PPS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.77
Mean Difference (Final Values) [5] 0.65
95% Confidence Interval -3.73 to 5.03
Standard Error of the mean (2.20)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



5.  Secondary:   Change in Alzheimer‘s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Secondary
Measure Title Change in Alzheimer‘s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Measure Description The ADAS-Cog primarily measures cognitive ability. The version used in this study was comprised of 12 items with scores ranging from 0 to 75. Higher scores suggest greater cognitive impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and completed the baseline visit and at least one post-baseline visit.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 82   84   0   0 
Change in Alzheimer‘s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -8.239  (1.531)   -10.796  (1.540)       


Statistical Analysis 1 for Change in Alzheimer‘s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.18
Mean Difference (Final Values) [5] -2.56
95% Confidence Interval -6.33 to 1.22
Standard Error of the mean (1.90)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



6.  Secondary:   Change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Secondary
Measure Title Change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Measure Description The CDR-SB consists of 6 items; 3 measuring cognitive ability and 3 measuring functional ability. The score for each of the six items range from 0 to 3; hence the total score is between 0 and 18. Higher scores suggest greater cognitive impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and completed the baseline visit and at least one post-baseline visit.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 82   84   0   0 
Change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -2.742  (0.363)   -2.452  (0.357)       


Statistical Analysis 1 for Change in Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.54
Mean Difference (Final Values) [5] 0.29
95% Confidence Interval -0.63 to 1.21
Standard Error of the mean (0.47)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



7.  Secondary:   Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)   [ Time Frame: Baseline and 78 weeks ]

Measure Type Secondary
Measure Title Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Measure Description The NPI is used to obtain information on the presence of severity of neuropsychological symptoms, and was specifically designed for use in Alzheimer's disease subjects. The scale consists of 12 items with each item having outcomes from 0 to 12; hence the total score ranges from 0 to 144. Higher scores suggest greater psychiatric impairment.
Time Frame Baseline and 78 weeks  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS): all randomized patients who received at least one dose of study drug and completed the baseline visit and at least one post-baseline visit.

Reporting Groups
  Description
Placebo BID oral administration for 78 weeks
ELND005 250 mg BID oral administration for 78 weeks
ELND005 1000 mg BID oral administration for 78 weeks
ELND005 2000 mg BID oral administration for 78 weeks

Measured Values
   Placebo BID   ELND005 250 mg BID   ELND005 1000 mg BID   ELND005 2000 mg BID 
Participants Analyzed 
[Units: Participants]
 		 82   84   0   0 
Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS) 
[Units: Scores on a Scale]
Mean (Standard Error) 		 -6.132  (1.851)   -5.116  (1.814)       


Statistical Analysis 1 for Change in Neuropsychiatric Inventory (NPI) Score From Baseline to Week 78 (Full Analysis Set; FAS)
Groups [1] Placebo BID vs. ELND005 250 mg BID
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.65
Mean Difference (Final Values) [5] 1.02
95% Confidence Interval -3.43 to 5.46
Standard Error of the mean (2.24)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The two high dose groups of ELND005 were discontinued before study end, so the efficacy analysis was based only on placebo and ELND005 250 mg bid groups.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Aleksandra pastrak, MD, PhD, Vice President, Clinical Development
Organization: Transition Therapeutics Ireland Limited
phone: +1 416 263 1227
e-mail: apastrak@transitiontherapeutics.com



Responsible Party: Transition Therapeutics Ireland Limited
ClinicalTrials.gov Identifier: NCT00568776     History of Changes
Other Study ID Numbers: ELND005-AD201
First Submitted: December 4, 2007
First Posted: December 6, 2007
Results First Submitted: September 27, 2011
Results First Posted: March 29, 2012
Last Update Posted: May 16, 2016