This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

Study Evaluating The Safety Of AAB-003 (PF-05236812) In Subjects With Alzheimer's Disease

This study has been completed.
Sponsor:
Collaborator:
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01193608
First received: August 19, 2010
Last updated: January 3, 2017
Last verified: January 2017
August 19, 2010
January 3, 2017
September 2010
October 2013   (Final data collection date for primary outcome measure)
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]
  • Number of Participants With Laboratory Abnormalities [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]
  • Number of Participants With Vital Signs of Potential Clinical Concern [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]
    Criteria for potential clinical concern in vital signs included: supine/sitting pulse rate of less than (<) 40 or more than (>) 120 beats per minute (bpm), and standing pulse rate of <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 and <90 mm Hg; diastolic blood pressure (DBP) >=20 mm Hg change from baseline in same posture and <50 mm Hg. Only supine vital signs were planned for this study. Unplanned sitting vital signs were collected only in the 8/mg and placebo groups and also reported.
  • Number of Participants With Abnormal Physical Examination Findings [ Time Frame: Baseline up to 39 Weeks and at Early Withdrawal ]
  • Number of Participants With Abnormal Neurological Examination Findings [ Time Frame: Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal ]
    The neurological examination was done to the extent needed to assess the participant for any potential changes in neurological status, as determined by the investigator. The minimum items assessed were level of consciousness, speech, cranial nerves, motor, sensory, coordination, gait, and tendon reflexes.
  • Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Average Concentration (Cavg) for AAB-003 in Serum at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Average Concentration (Cavg) for AAB-003 in Serum at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Systemic Clearance (CL) for AAB-003 in Serum at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Systemic Clearance (CL) for AAB-003 in Serum at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Serum Decay Half-Life (t1/2) for AAB-003 at Day 1 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion. ]
  • Serum Decay Half-Life (t1/2) for AAB-003 at Week 26 [ Time Frame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion. ]
  • Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline up to Week 39 or Early Withdrawal ]
    The C-SSRS assessed whether the participant experienced the following: completed suicide (1), suicide attempt (2) (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior (3)("Yes" on "preparatory acts or behavior"), suicidal ideation (4) ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior (7)("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").
  • Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding [ Time Frame: Baseline up to Week 32. ]
    Brain MRIs were collected during the course of study to assess for any potential drug-related changes that might have constituted a safety concern for study participants. Findings suggestive of either vasogenic edema (VE) or intracranial hemorrhage represented adverse events of special circumstance and were to be reported immediately.
  • Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit [ Time Frame: Day 1, Week 13, and Week 26 ]
    VE of the brain, identified via MRI, was identified as an adverse event of special circumstance.
  • Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria [ Time Frame: Baseline, Weeks 1,13,16,26,39 or Early Withdrawal ]
    Criteria for ECG values of potential clinical concern are: interval between the start of the ECG P wave and the start of the QRS complex corresponding to the time between onset of atrial depolarization and onset of ventricular depolarization (PR): >= 300 milliseconds (msec), and >=25% increase when baseline >=200 msec/ >=50% increase when baseline less than or equal to (<=) 200 msec; time from ECG Q wave to the end of S wave corresponding to ventricular depolarization (QRS): >=200 msec, and >=25% increase when baseline >100 msec/ >=50% increase when baseline <=100 msec; QTc using Fridericia's formula (QTcF) interval: 450 to <480 msec, >=480 msec; QTcF change from baseline: 30 to <60 msec, and >=60 msec.
  • Adverse events, clinical laboratory results, vital signs, physical and neurological examinations, ECGs, Columbia Severity Rating Scale (C-SSRS), magnetic resonance imaging (MRI) of the brain. [ Time Frame: Week 39 ]
  • Pharmacokinetic parameters for AAB-003 [ Time Frame: Week 39 ]
Complete list of historical versions of study NCT01193608 on ClinicalTrials.gov Archive Site
Not Provided
  • The presence of anti-product antibodies to AAB-003 will be determined in serum. [ Time Frame: Week 39 ]
  • Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) [ Time Frame: Week 39 ]
  • Disability Assessment in Dementia (DAD) [ Time Frame: Week 39 ]
  • Neuropsychiatric Inventory (NPI) [ Time Frame: Week 39 ]
  • Clinical Dementia Rating Sum of Boxes (CDR-SB) [ Time Frame: Week 39 ]
  • Mini Mental State Exam (MMSE) [ Time Frame: Week 39 ]
  • Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum [ Time Frame: Day 1 (predose), Week 13 (predose), Week 26 (predose) and Week 39 or Early Withdrawal ]
    Human serum anti-drug antibodies (ADA) samples were analyzed for the presence or absence of anti-AAB-003 antibodies by enzyme-linked immunosorbent assay (ELISA) method
  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39 [ Time Frame: Baseline, Weeks 13, 26 and 39 ]
    The ADAS-cog 70 Point is a structured scale (approximately 40 min to complete) that evaluates memory, orientation, attention, reasoning, language and constructional praxis. This study used the 11-item cognitive subscale of the ADAS-Cog with scores ranging from 0 to 70 points; higher scores indicated greater cognitive impairment.
  • Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39 [ Time Frame: Baseline, Weeks 13, 26 and 39 ]
    The DAD is a functional assessment based on an interview with the caregiver that takes approximately 20 min to administer and it is comprised of 40 items, 17 related to self-care and 23 items involving instrumental activities of daily living. The DAD is scored from 0 to 100 (higher scores indicate better functioning).
  • Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39 [ Time Frame: Baseline, Weeks 13, 26 and 39 ]
    The NPI is an instrument used to assess changes of behavior that have appeared in a defined period of time in participants with Alzheimer's disease (AD) and other dementias. Twelve (12) behavioral areas are assessed in the NPI - 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 as reported by the caregiver. A separate caregiver distress score may also be included. The NPI ranges from 0 to 144 (higher scores indicate greater psychopathology).
  • Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39 [ Time Frame: Baseline, Weeks 26 and 39 ]
    The CDR scale is a clinician-rated 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 based on the CDR interview. The CDR is based on discussions between the clinician with the participant and caregiver using a structured format. A global CDR score is established by clinical scoring rules with values of 0 (no dementia), 0.5 (questionable dementia), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). A more quantitative version of the CDR scale is obtained by summing up the ratings in each of the 6 categories to provide the (CDR-SB). The CDR-SB scale ranges from 0 to 18 where higher score indicates severe dementia.
  • Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39 [ Time Frame: Baseline, Weeks 13, 26 and 39 ]
    The MMSE is a brief 30-point questionnaire test that is used to assess cognition. It is commonly used to screen for dementia. In the time span of about 10 min, it samples various functions, including arithmetic, memory and orientation. Scores range from 0 to 30 (higher scores indicate less impairment) and participants with scores of 16 to 26 were eligible.
  • Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32 [ Time Frame: Week 32 or Early Withdrawal ]
    Participants enrolled in the 2, 4 and 8 mg/kg cohorts participated in an optional CSF collection. Participants enrolled in the maximum tolerated dose (MTD) cohort were mandatorily collected for CSF.
  • Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups [ Time Frame: Baseline and Week 32 ]
  • CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups [ Time Frame: Baseline and Week 32 ]
  • Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups [ Time Frame: Baseline and Week 32 ]
  • CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups [ Time Frame: Baseline and Week 32 ]
  • Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups [ Time Frame: Baseline and Week 32 ]
  • CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups [ Time Frame: Baseline and Week 32 ]
  • Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups [ Time Frame: Baseline and Week 32 ]
  • CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups [ Time Frame: Baseline and Week 32 ]
  • Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40 [ Time Frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40 [ Time Frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40 [ Time Frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40 [ Time Frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]
  • Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40 [ Time Frame: Weeks 1, 3, 6, 10, 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]
  • Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40 [ Time Frame: Baseline; Day 2 (24 hours post start of infusion); Weeks 1, 6, and 13 (pre-dose, 1 hour [end of infusion]), Week 26 (pre-dose, 1 hour [end of infusion], 1.5, 2, 4, 6, and 24 hours post start of infusion), and Weeks 32 and 39. ]
Not Provided
 
Study Evaluating The Safety Of AAB-003 (PF-05236812) In Subjects With Alzheimer's Disease
A Phase 1, Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptive, Multiple Ascending Dose Study Of The Safety, Tolerability And Pharmacokinetics Of Aab-003 (Pf-05236812) In Subjects With Mild To Moderate Alzheimer's Disease
This is a study to evaluate the safety of multiple doses of AAB-003 (PF-05236812) in patients with mild to moderate Alzheimer's Disease. Patients will receive either AAB-003 (PF-05236812) or placebo. Each patient's participation will last approximately 41 weeks.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alzheimer's Disease
  • 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
  • Other: Placebo
    Placebo, IV
  • 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)
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
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.
 
Completed
88
October 2013
October 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of probable Alzheimer's Disease with MMSE score of 16-26, and brain MRI consistent with the diagnosis of Alzheimer's Disease
  • Concurrent use of cholinesterase inhibitor or memantine allowed, if stable.
  • Caregiver will participate and be able to attend clinic visits with patient

Exclusion Criteria:

  • Significant neurological disease other than Alzheimer's Disease
  • Major psychiatric disorder
  • Contraindication to undergo brain MRI (e.g., pacemaker, CSF shunt, or foreign metal objects in the body)
  • Women of childbearing potential
Sexes Eligible for Study: All
50 Years to 89 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of,   United States
 
 
NCT01193608
B2601001
3245K1-1000 ( Other Identifier: Alias Study Number )
Yes
Not Provided
Not Provided
Pfizer
Pfizer
JANSSEN Alzheimer Immunotherapy Research & Development, LLC
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
January 2017

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