Clinical trial NCT01193608: Study Evaluating The Safety Of AAB-003 (PF-05236812) In Subjects With Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: Randomized
Safety Study
Adaptive
Double Blind
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: JANSSEN Alzheimer Immunotherapy Research & Development, LLC
First posted: 2010-09-02
Enrollment: 88
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 39 Weeks and at Early Withdrawal
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to 39 Weeks and at Early Withdrawal
measure: Number of Participants With Vital Signs of Potential Clinical Concern
timeFrame: Baseline up to 39 Weeks and at Early Withdrawal
measure: Number of Participants With Abnormal Physical Examination Findings
timeFrame: Baseline up to 39 Weeks and at Early Withdrawal
measure: Number of Participants With Abnormal Neurological Examination Findings
timeFrame: Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal
measure: Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Maximum Observed Serum Concentration (Cmax) for AAB-003 at at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Average Concentration (Cavg) for AAB-003 in Serum at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Average Concentration (Cavg) for AAB-003 in Serum at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) for AAB-003 at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for AAB-003 in Serum at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for AAB-003 in Serum at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for AAB-003 in Serum at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Systemic Clearance (CL) for AAB-003 in Serum at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Systemic Clearance (CL) for AAB-003 in Serum at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Volume of Distribution at Steady State (Vss) for AAB-003 in Serum at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Serum Decay Half-Life (t1/2) for AAB-003 at Day 1
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4 and 6 hours post start of infusion.
measure: Serum Decay Half-Life (t1/2) for AAB-003 at Week 26
timeFrame: Pre-dose, 1 hour (end of infusion), 1.5, 2, 4, 6, and 24 hours post start of infusion.
measure: Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to Week 39 or Early Withdrawal
measure: Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding
timeFrame: Baseline up to Week 32.
measure: Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit
timeFrame: Day 1, Week 13, and Week 26
measure: Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria
timeFrame: Baseline, Weeks 1,13,16,26,39 or Early Withdrawal
Secondary outcomes:
Other outcomes:
measure: Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum
timeFrame: Day 1 (predose), Week 13 (predose), Week 26 (predose) and Week 39 or Early Withdrawal
measure: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39
timeFrame: Baseline, Weeks 13, 26 and 39
measure: Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39
timeFrame: Baseline, Weeks 13, 26 and 39
measure: Change From Baseline in Behavioral Symtoms as Measured by the Neuropsychiatric Inventory (NPI) at Weeks 13, 26 and 39
timeFrame: Baseline, Weeks 13, 26 and 39
measure: Change From Baseline on the Clinical Dementia Rating (CDR) Sum of Boxes (CDR-SB) and Global CDR Rating at Weeks 26 and 39
timeFrame: Baseline, Weeks 26 and 39
measure: Change From Baseline on the Mini Mental State Exam (MMSE) Score at Weeks 13, 26, and 39
timeFrame: Baseline, Weeks 13, 26 and 39
measure: Cerebrospinal Fluid (CSF) Concentration of AAB-003 at Week 32
timeFrame: Week 32 or Early Withdrawal
measure: Change From Baseline in CSF Amyloid-beta x-40 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
timeFrame: Baseline and Week 32
measure: CSF Amyloid-beta x-40 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
timeFrame: Baseline and Week 32
measure: Change From Baseline in CSF Amyloid-beta x-42 Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
timeFrame: Baseline and Week 32
measure: CSF Amyloid-beta x-42 Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
timeFrame: Baseline and Week 32
measure: Change From Baseline in CSF Tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
timeFrame: Baseline and Week 32
measure: CSF Tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
timeFrame: Baseline and Week 32
measure: Change From Baseline in CSF P-tau Concentration at Week 32 for AAB-003 8 mg/kg and Placebo Groups
timeFrame: Baseline and Week 32
measure: CSF P-tau Concentration at Baseline and Week 32 for AAB-003 2 mg/kg and 4 mg/kg Groups
timeFrame: Baseline and Week 32
measure: Maximum Observed Plasma Concentration (Cmax) for Amyloid-Beta x-40
timeFrame: 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.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Amyloid-Beta x-40
timeFrame: 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.
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Amyloid-Beta x-40
timeFrame: 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.
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Amyloid-Beta x-40
timeFrame: 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.
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amyloid-Beta x-40
timeFrame: 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.
measure: Plasma Decay Half-Life (t1/2) for Amyloid-Beta x-40
timeFrame: 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.
Locations:
city: Escondido
country: United States
facility: Early Phase Investigational Center
state: California
city: Escondido
country: United States
facility: Synergy Clinical Research Center of Escondido
state: California
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Ocala
country: United States
facility: Franck's Pharmacy
state: Florida
city: Ocala
country: United States
facility: Munroe Regional Medical Center
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Ocala
country: United States
facility: Advanced Imaging of Ocala
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Bethesda
country: United States
facility: Foers Medical Arts Pharmacy
state: Maryland
city: Rockville
country: United States
facility: CBH Health, LLC
state: Maryland
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Research Institute
state: Michigan
city: Kalamazoo
country: United States
facility: KNI/Southwest Michigan Imaging Center, LLC
state: Michigan
city: Flowood
country: United States
facility: Brentwood Behavioral Healthcare
state: Mississippi
city: Flowood
country: United States
facility: Marty's Pharmacy
state: Mississippi
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Creve Coeur
country: United States
facility: Millennium Psychiatric Associates, LLC
state: Missouri
city: St. Louis
country: United States
facility: DePaul Health Center
state: Missouri
city: Eatontown
country: United States
facility: Memory Enhancement Center of America, Inc.
state: New Jersey
city: Edison
country: United States
facility: Pharmacare USA
state: New Jersey
city: Oakhurst
country: United States
facility: Central Jersey Radiology
state: New Jersey
city: Philadelphia
country: United States
facility: Belmont Center for Comprehensive Treatment
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital, Department of Neurology
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital, Department of Neurology
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Department of Neurology
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center, Department of Neurology
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.