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

NCT01193608 | Completed Phase 1 Results DMC

• 2 other identifiers: B26010013245K1-1000
• Study Type: interventional
• Target: 88
• Locations: 2 countries
• Sites: 29

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.

Conditions

Alzheimer's Disease

Keywords

Randomized; Safety Study; Adaptive; Double Blind

Outcome Measures

Primary Outcomes (25)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to 39 Weeks and at Early Withdrawal

• Number of Participants With Laboratory Abnormalities

  Baseline up to 39 Weeks and at Early Withdrawal

• Number of Participants With Vital Signs of Potential Clinical Concern

  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.

  Baseline up to 39 Weeks and at Early Withdrawal

• Number of Participants With Abnormal Physical Examination Findings

  Baseline up to 39 Weeks and at Early Withdrawal

• Number of Participants With Abnormal Neurological Examination Findings

  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.

  Screening, Day 1 (Baseline) and Weeks 1,6,13,19,26,32, and 39, and at Early Withdrawal

• Maximum Observed Serum Concentration (Cmax) for AAB-003 at Day 1

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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

  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)

  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").

  Baseline up to Week 39 or Early Withdrawal

• Number of Participants With New Occurrence of Brain Magnetic Resonance Imaging (MRI) Finding

  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.

  Baseline up to Week 32.

• Number of Participants With Vasogenic Edema of All Severity After Each Infusion Visit

  VE of the brain, identified via MRI, was identified as an adverse event of special circumstance.

  Day 1, Week 13, and Week 26

• Number of Participants With Change From Baseline and Absolute Values in Electrocardiogram (ECG) Meeting Categorical Summarization Criteria

  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.

  Baseline, Weeks 1,13,16,26,39 or Early Withdrawal

Other Outcomes (21)

• Number of Participants With Positive Anti-product Antibody Response to AAB-003 in Serum

  Day 1 (predose), Week 13 (predose), Week 26 (predose) and Week 39 or Early Withdrawal

• Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Score at Weeks 13, 26 and 39

  Baseline, Weeks 13, 26 and 39

• Change From Baseline in Disability Assessment in Dementia (DAD) Score at Weeks 13, 26 and 39

  Baseline, Weeks 13, 26 and 39

Study Arms (6)

0.5 mg/kg AAB-003

EXPERIMENTAL

Drug: AAB-003 (PF-05236812)

1 mg/kg AAB-003

EXPERIMENTAL

Drug: AAB-003 (PF-05236812)

2 mg/kg AAB-003

EXPERIMENTAL

Drug: AAB-003 (PF-05236812)

4 mg/kg AAB-003

EXPERIMENTAL

Drug: AAB-003 (PF-05236812)

8 mg/kg AAB-003

EXPERIMENTAL

Drug: AAB-003 (PF-05236812)

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

AAB-003 (PF-05236812) DRUG

0.5 mg/kg AAB-003, IV

0.5 mg/kg AAB-003

Placebo OTHER

Placebo, IV

Placebo

Eligibility Criteria

• Age: 50 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead
• JANSSEN Alzheimer Immunotherapy Research & Development, LLC: collaborator

Study Sites (29)

Early Phase Investigational Center

Escondido, California, 92025, United States

Location

Synergy Clinical Research Center of Escondido

Escondido, California, 92025, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Franck's Pharmacy

Ocala, Florida, 34471, United States

Location

Munroe Regional Medical Center

Ocala, Florida, 34471, United States

Location

Renstar Medical Research

Ocala, Florida, 34471, United States

Location

Advanced Imaging of Ocala

Ocala, Florida, 34481, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30308, United States

Location

Foers Medical Arts Pharmacy

Bethesda, Maryland, 20814, United States

Location

CBH Health, LLC

Rockville, Maryland, 20850, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49048, United States

Location

Borgess Research Institute

Kalamazoo, Michigan, 49048, United States

Location

KNI/Southwest Michigan Imaging Center, LLC

Kalamazoo, Michigan, 49048, United States

Location

Brentwood Behavioral Healthcare

Flowood, Mississippi, 39232, United States

Location

Marty's Pharmacy

Flowood, Mississippi, 39232, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, 63141, United States

Location

DePaul Health Center

St Louis, Missouri, 63044, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

Pharmacare USA

Edison, New Jersey, 08837, United States

Location

Central Jersey Radiology

Oakhurst, New Jersey, 07755, United States

Location

Belmont Center for Comprehensive Treatment

Philadelphia, Pennsylvania, 19131-1689, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Seoul National University Bundang Hospital, Department of Neurology

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Inha University Hospital, Department of Neurology

Incheon, South Korea

Location

Samsung Medical Center, Department of Neurology

Seoul, 135-710, South Korea

Location

Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

ASAN Medical Center

Seoul, 138-736, South Korea

Location

Konkuk University Medical Center, Department of Neurology

Seoul, 143-914, South Korea

Location

Related Publications (1)

• 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.

  PMID: 26925577 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2010
• First Posted: September 2, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: February 23, 2017
• Results First Posted: February 23, 2017

Record last verified: 2017-01

Locations

US (23); KR (6)