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

NCT01369225 | Completed Phase 1 Results

• 1 other identifier: B2601003
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 21

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.

Conditions

Alzheimer's Disease

Keywords

Randomized; Safety Study; Open Label

Outcome Measures

Primary Outcomes (8)

• 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.

  Baseline up to Week 52

• 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).

  Baseline up to Week 52

• 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.

  Baseline up to Week 52

• 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.

  Baseline up to Week 52

• 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.

  Baseline up to Week 52

• 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.

  Baseline up to Week 52

• 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.

  Baseline up to Week 52

• 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.

  Baseline up to Week 52

Other Outcomes (6)

• Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer

  Baseline, Week 52

• Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Scores at Week 52

  Baseline, Week 52

• Change From Baseline in Disability Assessment in Dementia (DAD) at Week 52

  Baseline, Week 52

Study Arms (5)

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)

Interventions

AAB-003 (PF-05236812) DRUG

0.5 mg/kg AAB-003, IV

0.5 mg/kg AAB-003

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Successful completion of study B2601001
• MMSE 12 or greater

You may not qualify if:

• Experienced SAE, vasogenic edema and/or intracranial hemorrhage in study B2601001

Sponsors & Collaborators

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

Study Sites (21)

MD Clinical

Hallandale, Florida, 33009, United States

Location

Munroe Regional Medical Center

Ocala, Florida, 34471, United States

Location

Renstar Medical Research

Ocala, Florida, 34471, United States

Location

Trinity Care Solutions

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

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, 63141, United States

Location

DePaul Health Center-MRI Department

St Louis, Missouri, 63044, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

Central Jersey Radiology

Oakhurst, New Jersey, 07755, United States

Location

Seoul National University Hospital, Department Neurology

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

Location

Inha University Hospital, Department of Neurology

Incheon, 400-711, South Korea

Location

Samsung Medical Center, Department of Neurology

Seoul, 1350710, South Korea

Location

Korea University Anam Hospital IRB

Seoul, 136-705, South Korea

Location

ASAN Medical Center

Seoul, 138-736, South Korea

Location

Konkuk University Medical Center, Department of Neurology

Seoul, 143914, 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2011
• First Posted: June 8, 2011
• Study Start: July 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 10, 2017
• Results First Posted: March 10, 2017

Record last verified: 2017-01

Locations

US (15); KR (6)