A Long-Term Safety And Tolerability Extension Study Of Bapineuzumab In Alzheimer Disease Patients

• ClinicalTrials.gov Identifier: NCT00998764
• Recruitment Status: Terminated
• First Posted: October 20, 2009
• Results First Posted: January 1, 2016
• Last Update Posted: January 1, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 16, 2009
• First Posted Date: October 20, 2009
• Results First Submitted Date: October 15, 2013
• Results First Posted Date: January 1, 2016
• Last Update Posted Date: January 1, 2016
• Study Start Date: December 2009
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2015)

Number of Participants Reporting a Serious Adverse Event [ Time Frame: Up to Week 195 ]

Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.

Original Primary Outcome Measures (submitted: October 19, 2009)

• Incidence and severity of treatment emergent adverse events [ Time Frame: 2 years ]
• Clinically important changes in vital signs [ Time Frame: 2 years ]
• Weight [ Time Frame: 2 years ]
• Electrocardiogram (ECG) [ Time Frame: 2 years ]
• Laboratory determinations [ Time Frame: 2 years ]
• Brain magnetic resonance imaging (MRI) [ Time Frame: 2 years ]
• Physical and neurological examinations [ Time Frame: 2 years ]
• Infusion site assessments [ Time Frame: 2 years ]

Current Secondary Outcome Measures (submitted: November 30, 2015)

• Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]
  The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8 remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.
• Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]
  The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8)remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.
• Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]
  The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.
• Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]
  The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.
• Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. [ Time Frame: Base Study Baseline, Weeks 26, 52 and 78 ]
  NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.
• Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. [ Time Frame: Base Study Baseline, Weeks 26, 52 and 78 ]
  NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.
• Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. [ Time Frame: Base Study Baseline, Weeks 6, 19, 32, 45 and 78 ]
  MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.
• Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. [ Time Frame: Base Study Baseline, Weeks 6, 19, 32, 45 and 78 ]
  MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.

Original Secondary Outcome Measures (submitted: October 19, 2009)

• Alzheimer's Disease Assessment Scale-Cognitive Subscale [ Time Frame: 2 years ]
• Disability Assessment for Dementia [ Time Frame: 2 years ]
• Neuropsychiatric Inventory [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Long-Term Safety And Tolerability Extension Study Of Bapineuzumab In Alzheimer Disease Patients
• Official Title: A Phase 3 Extension, Multicenter, Long Term Safety And Tolerability Trial Of Bapineuzumab (Aab 001, Eln115727) In Subjects With Alzheimer Disease Who Are Apolipoprotein E 4 Carriers And Participated In Study 3133k1-3001-us Or Study 3133k1-3001-ww.
• Brief Summary: The purpose of this study is to assess the long-term safety and tolerability of bapineuzumab in subjects with Alzheimer Disease who participated in study 3133K1-3001(NCT00676143). Over 250 sites will participate in over 26 countries. Subjects will receive bapineuzumab. Each subject's participation will last approximately 4 years.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alzheimer Disease

Intervention

Drug: Bapineuzumab 0.5 mg/kg

I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.

Other Name: AAB-001

Study Arms

Experimental: Bapineuzumab 0.5 mg/kg

Intervention: Drug: Bapineuzumab 0.5 mg/kg

• Publications *: Ivanoiu A, Pariente J, Booth K, Lobello K, Luscan G, Hua L, Lucas P, Styren S, Yang L, Li D, Black RS, Brashear HR, McRae T. Long-term safety and tolerability of bapineuzumab in patients with Alzheimer's disease in two phase 3 extension studies. Alzheimers Res Ther. 2016 Jun 23;8(1):24. doi: 10.1186/s13195-016-0193-y.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 30, 2015): 494
• Original Estimated Enrollment (submitted: October 19, 2009): 800
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject has completed study 3133K1-3001 (Week 78) and brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of Alzheimer Disease
• Mini-Mental Status Examination (MMSE) >=10 at screening
• Caregiver able to attend all clinic visits with subject

Exclusion Criteria:

• Any medical or psychiatric contraindication or clinically significant abnormality that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response.
• Any significant brain MRI abnormality.
• Use of any investigational drugs or devices, other than bapineuzumab within the last 60 days prior to screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 51 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Chile, Finland, France, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Slovakia, South Africa, Spain, Sweden, Switzerland, United Kingdom, United States
• Removed Location Countries: Mexico

Administrative Information

• NCT Number: NCT00998764
• Other Study ID Numbers: 3133K1-3003; B2521004 ( Other Identifier: Alias Study Number ); 2009-015080-13 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Wyeth (Registry Contact: Clinical Trial Registry Specialist), Wyeth
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2015