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Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AAB-003 (PF-05236812)
AAB-003 (PF-05236812)
AAB-003 (PF-05236812)
AAB-003 (PF-05236812)
AAB-003 (PF-05236812)
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Randomized, Safety Study, Open Label

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Successful completion of study B2601001
  • MMSE 12 or greater

Exclusion Criteria:

  • Study B2601001 Week 32 MRI with clinically important exclusionary findings.
  • Experienced SAE, vasogenic edema and/or intracranial hemorrhage in study B2601001

Sites / Locations

  • MD Clinical
  • Munroe Regional Medical Center
  • Renstar Medical Research
  • Trinity Care Solutions
  • Advanced Imaging of Ocala
  • Atlanta Center for Medical Research
  • Foers Medical Arts Pharmacy
  • CBH Health, LLC
  • Borgess Medical Center
  • Borgess Research Institute
  • KNI Southwest Michigan Imaging Center, LLC
  • Millennium Psychiatric Associates, LLC
  • DePaul Health Center-MRI Department
  • Memory Enhancement Center of America, Inc.
  • Central Jersey Radiology
  • Seoul National University Hospital, Department Neurology
  • Inha University Hospital, Department of Neurology
  • Samsung Medical Center, Department of Neurology
  • Korea University Anam Hospital IRB
  • ASAN Medical Center
  • Konkuk University Medical Center, Department of Neurology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

0.5 mg/kg AAB-003

1 mg/kg AAB-003

2 mg/kg AAB-003

4 mg/kg AAB-003

8 mg/kg AAB-003

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, RBC morphology, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (coagulation panel, circulating immune complex, and complement activation).
Number of Participants With Potentially Clinically Important Vital Sign Findings
Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm); standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of more than or equal to (>=)30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mmHg change from baseline in same posture or DBP <50 mm Hg.
Number of Participants With Potentially Clinically Important Electrocardiogram (ECG) Findings
ECG parameters included PR interval, QRS interval, and QT interval. Criteria for ECG changes meeting potential clinical concern included: PR interval >=300 milliseconds (msec) or >=25% increase when baseline is >200 msec and >=50% increase when baseline is less than or equal to (<=)200 msec; QRS interval >=200 msec or >=50% increase from baseline when baseline is less than or equal to 100 msec and >=25% increase when baseline is >100 msec; and QTcF >=450 msec or >=30 msec increase.
Number of Participants With Abnormal Physical Examination Findings
A full physical examination consisted of an examination of the abdomen, genitourinary and cardiovascular systems, lungs, lymph nodes, mouth, musculoskeletal and neurological systems, skin, extremities, head, ears, eyes, nose, throat and thyroid gland. Criteria for abnormal physical findings was based on the investigator's discretion and any new physical examination findings were documented as AEs. Only sites with at least 1 participant abnormality are reported.
Number of Participants With Abnormal Neurological Examination Findings
Neurological examinations were done to the extent needed to assess the subject for any potential changes in neurological status, as determined by the investigator. Examinations included level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes. Only tests with at least 1 participant abnormality are reported.
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. C-SSRS assesses whether participant experienced the following: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. The results presented are the number of participants with completed suicide or non-fatal suicide events or behaviors. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
Number of Participants With Any New Magnetic Resonance Imaging (MRI) Findings
Brain MRIs were collected to assess for potential drug-related changes that might have constituted a safety concern. Findings suggestive of either vasogenic edema or intracranial hemorrhage were to be reported as AEs of special circumstance.

Secondary Outcome Measures

Full Information

First Posted
May 10, 2011
Last Updated
January 19, 2017
Sponsor
Pfizer
Collaborators
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01369225
Brief Title
Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer's Disease
Official Title
A Multicenter, Open-label Extension, Multiple Dose, Parallel Group Study To Investigate The Long-term Safety And Tolerability Of Aab-003 (Pf-05236812) Administered Intravenously In Subjects With Mild To Moderate Alzheimer's Disease Previously Treated With Aab-003 Or Placebo In Protocol B2601001
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
Collaborators
JANSSEN Alzheimer Immunotherapy Research & Development, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a study to evaluate the safety and tolerability of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients who complete study B2601001 may participate in this trial and receive AAB-003 (PF-05236812). Each patient's participation will last approximately 52 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Randomized, Safety Study, Open Label

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0.5 mg/kg AAB-003
Arm Type
Experimental
Arm Title
1 mg/kg AAB-003
Arm Type
Experimental
Arm Title
2 mg/kg AAB-003
Arm Type
Experimental
Arm Title
4 mg/kg AAB-003
Arm Type
Experimental
Arm Title
8 mg/kg AAB-003
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AAB-003 (PF-05236812)
Intervention Description
0.5 mg/kg AAB-003, IV
Intervention Type
Drug
Intervention Name(s)
AAB-003 (PF-05236812)
Intervention Description
1 mg/kg AAB-003, IV
Intervention Type
Drug
Intervention Name(s)
AAB-003 (PF-05236812)
Intervention Description
2 mg/kg AAB-003, IV
Intervention Type
Drug
Intervention Name(s)
AAB-003 (PF-05236812)
Intervention Description
4 mg/kg AAB-003, IV
Intervention Type
Drug
Intervention Name(s)
AAB-003 (PF-05236812)
Intervention Description
8 mg/kg AAB-003, IV
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Time Frame
Baseline up to Week 52
Title
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern
Description
The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, RBC morphology, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen [BUN], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (coagulation panel, circulating immune complex, and complement activation).
Time Frame
Baseline up to Week 52
Title
Number of Participants With Potentially Clinically Important Vital Sign Findings
Description
Vital signs assessment included pulse rate and blood pressure. Criteria for vital sign values meeting potential clinical concern included: supine/sitting pulse rate <40 or >120 beats per minute (bpm); standing pulse rate <40 or >140 bpm; systolic blood pressure (SBP) of more than or equal to (>=)30 millimeters of mercury (mm Hg) change from baseline in same posture or SBP <90 mm Hg, diastolic blood pressure (DBP) >=20 mmHg change from baseline in same posture or DBP <50 mm Hg.
Time Frame
Baseline up to Week 52
Title
Number of Participants With Potentially Clinically Important Electrocardiogram (ECG) Findings
Description
ECG parameters included PR interval, QRS interval, and QT interval. Criteria for ECG changes meeting potential clinical concern included: PR interval >=300 milliseconds (msec) or >=25% increase when baseline is >200 msec and >=50% increase when baseline is less than or equal to (<=)200 msec; QRS interval >=200 msec or >=50% increase from baseline when baseline is less than or equal to 100 msec and >=25% increase when baseline is >100 msec; and QTcF >=450 msec or >=30 msec increase.
Time Frame
Baseline up to Week 52
Title
Number of Participants With Abnormal Physical Examination Findings
Description
A full physical examination consisted of an examination of the abdomen, genitourinary and cardiovascular systems, lungs, lymph nodes, mouth, musculoskeletal and neurological systems, skin, extremities, head, ears, eyes, nose, throat and thyroid gland. Criteria for abnormal physical findings was based on the investigator's discretion and any new physical examination findings were documented as AEs. Only sites with at least 1 participant abnormality are reported.
Time Frame
Baseline up to Week 52
Title
Number of Participants With Abnormal Neurological Examination Findings
Description
Neurological examinations were done to the extent needed to assess the subject for any potential changes in neurological status, as determined by the investigator. Examinations included level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes. Only tests with at least 1 participant abnormality are reported.
Time Frame
Baseline up to Week 52
Title
Number of Participants With Suicidal Ideation or Suicidal Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. C-SSRS assesses whether participant experienced the following: completed suicide; suicide attempt; preparatory acts towards imminent suicidal behavior; suicidal ideation; self-injurious behavior, no suicidal intent. The results presented are the number of participants with completed suicide or non-fatal suicide events or behaviors. Worsening of suicidal ideation was an increase in severity of suicidal ideation from baseline.
Time Frame
Baseline up to Week 52
Title
Number of Participants With Any New Magnetic Resonance Imaging (MRI) Findings
Description
Brain MRIs were collected to assess for potential drug-related changes that might have constituted a safety concern. Findings suggestive of either vasogenic edema or intracranial hemorrhage were to be reported as AEs of special circumstance.
Time Frame
Baseline up to Week 52
Other Pre-specified Outcome Measures:
Title
Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer
Description
Number of participants with positive sample(s) in the ADA assay and in the neutralizing anti-drug antibodies (NAb) assay. An endpoint titer >=6.64 corresponded to positive ADA category value. The number of participants who tested positive on 1 or more occasions is reported.
Time Frame
Baseline, Week 52
Title
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Scores at Week 52
Description
ADAS-Cog is a structured scale that evaluates memory, orientation, attention, reasoning, language and constructional praxis. The ADAS-Cog comprises 11 items that are summed to a total score ranging from 0 to 70, with higher scores indicate greater cognitive impairment.
Time Frame
Baseline, Week 52
Title
Change From Baseline in Disability Assessment in Dementia (DAD) at Week 52
Description
The DAD is a functional assessment comprised of 40 items (17 items related to self-care and 23 items involving instrumental activities of daily living). The DAD assessment is scored from 0 to 100; higher scores indicate better function.
Time Frame
Baseline, Week 52
Title
Change From Baseline in Neuropsychiatric Inventory (NPI) Behavioral Symptoms at Week 52
Description
The NPI is an instrument used to assess changes of behavior that have appeared in a defined period of time in subjects with Alzheimer's Disease and other dementias. Twelve behavioral areas are assessed: delusions, apathy, hallucinations, disinhibition, agitation, irritability, depression, aberrant motor behavior, anxiety, nighttime behaviors, euphoria, appetite, and eating changes. The NPI score is based on frequency and severity of specific behaviors within these categories. 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). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Time Frame
Baseline, Week 52
Title
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Scores at Week 52
Description
The CDR scale is a dementia staging instrument that tracks the progression of cognitive impairment in the following 6 categories: memory, orientation, judgment and problem solving, involvement in community affairs, home and hobbies, and personal care. The CDR-SB scale is obtained by summing the ratings in each of the 6 categories, ranging from 0 to 18. Higher scores indicate greater disease severity.
Time Frame
Baseline, Week 52
Title
Change From Baseline in Mini-Mental State Exam (MMSE) Scores at Week 52
Description
The MMSE is a brief 30-point questionnaire test that is used to assess cognition. Scores range from 0 to 30, with higher scores indicating better cognitive state.
Time Frame
Baseline, Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Successful completion of study B2601001 MMSE 12 or greater Exclusion Criteria: Study B2601001 Week 32 MRI with clinically important exclusionary findings. Experienced SAE, vasogenic edema and/or intracranial hemorrhage in study B2601001
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
MD Clinical
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
Munroe Regional Medical Center
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Trinity Care Solutions
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Advanced Imaging of Ocala
City
Ocala
State/Province
Florida
ZIP/Postal Code
34481
Country
United States
Facility Name
Atlanta Center for Medical Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Foers Medical Arts Pharmacy
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Facility Name
CBH Health, LLC
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Borgess Medical Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
Borgess Research Institute
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
KNI Southwest Michigan Imaging Center, LLC
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
Millennium Psychiatric Associates, LLC
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
DePaul Health Center-MRI Department
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63044
Country
United States
Facility Name
Memory Enhancement Center of America, Inc.
City
Eatontown
State/Province
New Jersey
ZIP/Postal Code
07724
Country
United States
Facility Name
Central Jersey Radiology
City
Oakhurst
State/Province
New Jersey
ZIP/Postal Code
07755
Country
United States
Facility Name
Seoul National University Hospital, Department Neurology
City
Seongnam-si
State/Province
Gyeonggi-do
ZIP/Postal Code
463-707
Country
Korea, Republic of
Facility Name
Inha University Hospital, Department of Neurology
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
Facility Name
Samsung Medical Center, Department of Neurology
City
Seoul
ZIP/Postal Code
1350710
Country
Korea, Republic of
Facility Name
Korea University Anam Hospital IRB
City
Seoul
ZIP/Postal Code
136-705
Country
Korea, Republic of
Facility Name
ASAN Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Konkuk University Medical Center, Department of Neurology
City
Seoul
ZIP/Postal Code
143914
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
26925577
Citation
Delnomdedieu M, Duvvuri S, Li DJ, Atassi N, Lu M, Brashear HR, Liu E, Ness S, Kupiec JW. First-In-Human safety and long-term exposure data for AAB-003 (PF-05236812) and biomarkers after intravenous infusions of escalating doses in patients with mild to moderate Alzheimer's disease. Alzheimers Res Ther. 2016 Mar 1;8(1):12. doi: 10.1186/s13195-016-0177-y.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B2601003&StudyName=Open%20Label%20Extension%20Study%20Evaluating%20Safety%20and%20Tolerability%20of%20AAB-003%20%28PF-05236812%29%20%20in%20Subject%20with%20Mild%20to%20Moderate%20Alzheimer%27s
Description
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Learn more about this trial

Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer's Disease

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