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Trial record 1 of 1 for:    NCT01369225
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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

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ClinicalTrials.gov Identifier: NCT01369225
Recruitment Status : Completed
First Posted : June 8, 2011
Results First Posted : March 10, 2017
Last Update Posted : March 10, 2017
Sponsor:
Collaborator:
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE May 10, 2011
First Posted Date  ICMJE June 8, 2011
Results First Submitted Date  ICMJE June 15, 2016
Results First Posted Date  ICMJE March 10, 2017
Last Update Posted Date March 10, 2017
Study Start Date  ICMJE July 2011
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 19, 2017)
  • Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 52 ]
    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 [ Time Frame: Baseline up to Week 52 ]
    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 [ Time Frame: Baseline up to Week 52 ]
    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 [ Time Frame: Baseline up to Week 52 ]
    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 [ Time Frame: Baseline up to Week 52 ]
    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 [ Time Frame: Baseline up to Week 52 ]
    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) [ Time Frame: Baseline up to Week 52 ]
    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 [ Time Frame: Baseline up to Week 52 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2011)
Adverse events, clinical laboratory results, vital signs, physical and neurological examinations, ECGs, Columbia Suicide Severity Rating Scale (C-SSRS), magnetic resonance imaging (MRI) of the brain. [ Time Frame: 52 weeks ]
Change History Complete list of historical versions of study NCT01369225 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2011)
  • The presence of anti-product antibodies to AAB-003 will be determined in serum [ Time Frame: 52 weeks ]
  • Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) [ Time Frame: 52 weeks ]
  • Disability Assessment in Dementia (DAD) [ Time Frame: 52 weeks ]
  • Neuropsychiatric Inventory (NPI) [ Time Frame: 52 weeks ]
  • Clinical Demential Rating Sum of Boxes (CDR-SB) [ Time Frame: 52 weeks ]
  • Mini Mental State Exam (MMSE) [ Time Frame: 52 weeks ]
  • CSF abeta, tau, p-tau, AAB-003 concentrations [ Time Frame: 52 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: January 19, 2017)
  • Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer [ Time Frame: Baseline, Week 52 ]
    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.
  • Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Scores at Week 52 [ Time Frame: Baseline, Week 52 ]
    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.
  • Change From Baseline in Disability Assessment in Dementia (DAD) at Week 52 [ Time Frame: Baseline, Week 52 ]
    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.
  • Change From Baseline in Neuropsychiatric Inventory (NPI) Behavioral Symptoms at Week 52 [ Time Frame: Baseline, Week 52 ]
    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.
  • Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) Scores at Week 52 [ Time Frame: Baseline, Week 52 ]
    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.
  • Change From Baseline in Mini-Mental State Exam (MMSE) Scores at Week 52 [ Time Frame: Baseline, Week 52 ]
    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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer's Disease
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: AAB-003 (PF-05236812)
    0.5 mg/kg AAB-003, IV
  • Drug: AAB-003 (PF-05236812)
    1 mg/kg AAB-003, IV
  • Drug: AAB-003 (PF-05236812)
    2 mg/kg AAB-003, IV
  • Drug: AAB-003 (PF-05236812)
    4 mg/kg AAB-003, IV
  • Drug: AAB-003 (PF-05236812)
    8 mg/kg AAB-003, IV
Study Arms  ICMJE
  • Experimental: 0.5 mg/kg AAB-003
    Intervention: Drug: AAB-003 (PF-05236812)
  • Experimental: 1 mg/kg AAB-003
    Intervention: Drug: AAB-003 (PF-05236812)
  • Experimental: 2 mg/kg AAB-003
    Intervention: Drug: AAB-003 (PF-05236812)
  • Experimental: 4 mg/kg AAB-003
    Intervention: Drug: AAB-003 (PF-05236812)
  • Experimental: 8 mg/kg AAB-003
    Intervention: Drug: AAB-003 (PF-05236812)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 26, 2014)
52
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2011)
104
Actual Study Completion Date  ICMJE August 2014
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01369225
Other Study ID Numbers  ICMJE B2601003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2017

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