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

• 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: Pfizer
• Collaborator: JANSSEN Alzheimer Immunotherapy Research & Development, LLC
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: AAB-003 (PF-05236812)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: July 2011
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: 0.5 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 0.5 mg/kg AAB-003, IV
Experimental: 1 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 1 mg/kg AAB-003, IV
Experimental: 2 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 2 mg/kg AAB-003, IV
Experimental: 4 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 4 mg/kg AAB-003, IV
Experimental: 8 mg/kg AAB-003	Drug: AAB-003 (PF-05236812); 8 mg/kg AAB-003, IV

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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).
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.

Other Outcome Measures:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Florida

MD Clinical

Hallandale Beach, Florida, United States, 33009

Munroe Regional Medical Center

Ocala, Florida, United States, 34471

Renstar Medical Research

Ocala, Florida, United States, 34471

Trinity Care Solutions

Ocala, Florida, United States, 34471

Advanced Imaging of Ocala

Ocala, Florida, United States, 34481

United States, Georgia

Atlanta Center for Medical Research

Atlanta, Georgia, United States, 30308

United States, Maryland

Foers Medical Arts Pharmacy

Bethesda, Maryland, United States, 20814

CBH Health, LLC

Rockville, Maryland, United States, 20850

United States, Michigan

Borgess Medical Center

Kalamazoo, Michigan, United States, 49048

Borgess Research Institute

Kalamazoo, Michigan, United States, 49048

KNI Southwest Michigan Imaging Center, LLC

Kalamazoo, Michigan, United States, 49048

United States, Missouri

Millennium Psychiatric Associates, LLC

Creve Coeur, Missouri, United States, 63141

DePaul Health Center-MRI Department

St. Louis, Missouri, United States, 63044

United States, New Jersey

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States, 07724

Central Jersey Radiology

Oakhurst, New Jersey, United States, 07755

Korea, Republic of

Seoul National University Hospital, Department Neurology

Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707

Inha University Hospital, Department of Neurology

Incheon, Korea, Republic of, 400-711

Samsung Medical Center, Department of Neurology

Seoul, Korea, Republic of, 1350710

Korea University Anam Hospital IRB

Seoul, Korea, Republic of, 136-705

ASAN Medical Center

Seoul, Korea, Republic of, 138-736

Konkuk University Medical Center, Department of Neurology

Seoul, Korea, Republic of, 143914

Sponsors and Collaborators

Pfizer

JANSSEN Alzheimer Immunotherapy Research & Development, LLC

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01369225
• Other Study ID Numbers: B2601003
• First Posted: June 8, 2011
• Results First Posted: March 10, 2017
• Last Update Posted: March 10, 2017
• Last Verified: January 2017

Keywords provided by Pfizer:

Randomized; Safety Study; Open Label

Additional relevant MeSH terms:

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