A Study to Evaluate the Impact of MABT5102A on Brain Amyloid Load and Related Biomarkers in Patients With Mild to Moderate Alzheimer's Disease

A Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter, Phase II Study to Evaluate the Impact of MABT5102A on Brain Amyloid Load and Related Biomarkers in Patients With Mild to Moderate Alzheimer's Disease

This is a Phase II, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the effects of MABT5102A on brain amyloid burden (as assessed by amyloid PET imaging) and other biomarkers in patients with mild to moderate Alzheimer's disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: MABT5102A; Drug: MABT5102A; Drug: placebo; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nancy, France, 54035
    • Hopital Central-CHU de Nancy; Pharmacie
  • Toulouse, France, 31059
    • Hôpital Casselardit; Cons memoire
  • Tours Cedex 9, France, 37044
    • Clinique Psychiatrique Univ
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08221
    • Hospital Mutua de Terrasa
  • Barcelona
    • BArcelon, Barcelona, Spain, 08034
      • Fundacio ACE
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Banner Alzheimer's Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Insitute
    • Tucson, Arizona, United States, 85704
      • NNS Clinical Research LLC
  • California
    • Fresno, California, United States, 93720
      • Margolin Brain Institute
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA)
    • Oxnard, California, United States, 93030
      • Pacific Neuroscience Med Grp
    • Palo Alto, California, United States, 94304
      • Stanford Univ Medical Center
    • Santa Rosa, California, United States, 95403
      • Redwood Regional Medical Group
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research; Center of Southwest Florida
    • Fort Myers, Florida, United States, 33912
      • Internal Med Assoc of Lee Cty
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Orlando, Florida, United States, 32806
      • Compass Research
  • Georgia
    • Decatur, Georgia, United States, 30033
      • DeKalb Neurology Associates
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosci Inst
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo; Center for Brain Research
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
  • New York
    • Manhasset, New York, United States, 11030
      • Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.
  • Ohio
    • Toledo, Ohio, United States, 43623
      • Neurology & Neuroscience Ctr of Ohio
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorder Association (NINCDS-ADRDA) criteria
• Mini-Mental State Examination (MMSE) score of 18-26 points at screening
• Geriatric Depression Scale (GDS-15) score of < 6
• Completion of 6 years of education (or good work history consistent with exclusion of mental retardation or other pervasive developmental disorders)
• For patients currently receiving treatment with approved AD treatments (AChE inhibitors or memantine): Treatment initiated and continued for at least the last 3 months prior to randomization, at a stable dose for at least the last 2 months prior to randomization

Exclusion Criteria:

• Severe or unstable medical condition that, in the opinion of the investigator or Sponsor, would interfere with the patient's ability to complete the study assessments or would require the equivalent of institutional or hospital care
• History or presence of clinically evident vascular disease potentially affecting the brain (e.g., stroke, clinically significant carotid or vertebral stenosis or plaque, aortic aneurysm, intracranial aneurysm, cerebral hemorrhage, arteriovenous malformation)
• History of severe, clinically significant (persistent neurologic deficit or structural brain damage) central nervous system trauma (e.g., cerebral contusion)
• Hospitalization within 4 weeks prior to screening
• Previous treatment with MABT5102A or any other therapeutic that targets Abeta
• Treatment with any biologic therapy within 5 half-lives or 3 months prior to screening, whichever is longer, with the exception of routinely recommended vaccinations, which are allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Subcutaneous cohort exp	Drug: MABT5102A; Repeating subcutaneous injection; Drug: MABT5102A; Repeating intravenous infusion
Experimental: Part 2: Intravenous cohort exp	Drug: MABT5102A; Repeating subcutaneous injection; Drug: MABT5102A; Repeating intravenous infusion
Placebo Comparator: Part 1: Subcutaneous cohort; Repeating subcutaneous injection	Drug: placebo; Repeating subcutaneous injection; Drug: placebo; Repeating intravenous infusion
Placebo Comparator: Part 2: Intravenous cohort; Repeating intravenous injection	Drug: placebo; Repeating subcutaneous injection; Drug: placebo; Repeating intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in brain amyloid load as assessed by amyloid PET imaging	Baseline to Week 69

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in cerebrospinal fluid (CSF) biomarkers relevant to Alzheimer's disease	Baseline to Week 69
Change in brain metabolism as assessed by 18F-fluorodeoxyglucose positron emission tomography (FDG PET) imaging	Baseline to Week 69
Change in Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS Cog) score	Baseline to Week 73

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Robert Paul, M.D., Ph.D., Genentech, Inc.

Publications and helpful links

General Publications

• Yoshida K, Moein A, Bittner T, Ostrowitzki S, Lin H, Honigberg L, Jin JY, Quartino A. Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2020 Jan 22;12(1):16. doi: 10.1186/s13195-020-0580-2.
• Salloway S, Honigberg LA, Cho W, Ward M, Friesenhahn M, Brunstein F, Quartino A, Clayton D, Mortensen D, Bittner T, Ho C, Rabe C, Schauer SP, Wildsmith KR, Fuji RN, Suliman S, Reiman EM, Chen K, Paul R. Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer's disease (BLAZE). Alzheimers Res Ther. 2018 Sep 19;10(1):96. doi: 10.1186/s13195-018-0424-5.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2011
• Primary Completion (Actual): April 30, 2014
• Study Completion (Actual): April 30, 2014

Study Registration Dates

• First Submitted: July 18, 2011
• First Submitted That Met QC Criteria: July 18, 2011
• First Posted (Estimate): July 19, 2011

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: July 10, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: ABE4955g; GN00762 (Other Identifier: Hoffmann-La Roche)