Phase III Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid Compared to Histopathology

NCT01020838 | Completed Phase 3 Results

• 2 other identifiers: 145952009-012569-79
• Study Type: interventional
• Target: 218
• Locations: 5 countries
• Sites: 19

Brief Summary

To determine the sensitivity and specificity of the visual assessment of tracer uptake in the Florbetaben PET images compared to histological verification of the presence or absence of cerebral β-amyloid in the respective histopathologic post mortem specimens as the standard of truth

Conditions

Alzheimer Disease

Keywords

Florbetaben; Amyloid beta-protein; Alzheimer's disease

Outcome Measures

Primary Outcomes (1)

• Sensitivity and Specificity of the Majority Read of Visual Assessment of Tracer Uptake Compared to Histological Verification of the Presence or Absence of Cerebral Beta-amyloid in Postmortem Specimens

  The sensitivity/specificity of the visual assessment were calculated based on the majority read assessment of regional tracer uptake. This result was derived from assessments by 3 independent readers for brain regions of a subject where a Standard of Truth (SOT) was available. The SOT for this analysis was a centralized histopathological determination of β-amyloid presence/absence based on both Bielschowsky silver and immunohistochemical staining. Based on the PET images, a brain region was classified as "normal" or "abnormal" depending on the presence or absence of regional tracer uptake in the respective region. "Normal" therefore meant absence of β-amyloid and "abnormal" presence of β-amyloid. Sensitivity was defined as the percentage of abnormal brain regions from all regions where an SOT was available and the SOT was "β-amyloid present". Specificity was defined as the percentage of normal brain regions from all regions where an SOT was available and was "β-amyloid not present".

  90-110 minutes post injection (PET image acquisition)

Secondary Outcomes (5)

• Sensitivity and Specificity of the Majority Read "Whole Brain" Visual Assessment in Detecting/Excluding Cerebral Neuritic β-amyloid Plaques Compared With the Histopathological Verification With Bielschowsky Silver Staining (SOT 1).

  90-110 minutes post injection (PET image acquisition)

• Sensitivity and Specificity of the Majority Read "Whole Brain" Visual Assessment in Detecting/Excluding Cerebral Neuritic β-amyloid Plaques Compared With Histopathological Verification With Bielschowsky Silver Staining and Immunohistochemistry (SOT 2).

  90-110 minutes post injection (PET image acquisition)

• Sensitivity and Specificity of the Majority Read "Whole Brain" Visual Assessment in Detecting/Excluding Cerebral Neuritic β-amyloid Plaques Compared With the Histopathological Verification According to CERAD Criteria (SOT 3).

  90-110 minutes post injection (PET image acquisition)

• Sensitivity and Specificity of the Subject Level Composite SUVR Calculated Based on Pathology Results.

  90-110 minutes post injection (PET image acquisition)

• Subject Level Composite SUVRs by SOT for Baseline and Available Follow-Up Scans

  90-110 minutes post injection (PET image acquisition)

Study Arms (1)

Florbetaben (BAY94-9172)

EXPERIMENTAL

Drug: Florbetaben (BAY94-9172)

Interventions

Florbetaben (BAY94-9172) DRUG

Single intravenous injection 1-5ml, 300 MBq (+/- 20%)

Florbetaben (BAY94-9172)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females, no child-bearing potential or negative urine pregnancy test on day of BAY94-9172 injection
• Exhibits visual, auditory, and communicative capabilities adequate to provide informed consent or assent and comply with study procedures
• Is willing and able to lie down in magnetic resonance imaging (MRI) and positron emission tomography (PET) scanners
• Is willing to donate their brain for postmortem examination in case of death
• The subject, or the subject and/or legally acceptable representative will be compliant and have a high probability of completing the study in the opinion of the investigator
• Has been fully informed about the study, including provisions of the Health Insurance Portability and Accountability Act (HIPAA), as applicable, and informed consent or assent has been signed and dated (with time) by the subject and/or the subject's legally acceptable representative

You may not qualify if:

• Has severe cerebral macrovascular (ie, multi-stroke) disease or brain tumor (metastasis/brain cancer) as verified by MRI
• Has any contraindication to magnetic resonance imaging (MRI) examination, eg, metal implants or phobia as determined by the onsite radiologist performing the scan
• Has been previously enrolled in this study or participated in a clinical study involving an investigational pharmaceutical product within 30 days prior to screening and/or was administered a radiopharmaceutical within 10 radioactive half-lives prior to study drug administration in this study
• Has severe cardio-vascular instability requiring intensive care surveillance and/or therapeutic intervention (i.e. catecholamine infusion)

Sponsors & Collaborators

• Life Molecular Imaging SA: lead

Study Sites (19)

Unknown Facility

Sun City, Arizona, 85351, United States

Location

Unknown Facility

Stanford, California, 94305, United States

Location

Unknown Facility

Tampa, Florida, 33616, United States

Location

Unknown Facility

Teaneck, New Jersey, 07666, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Dallas, Texas, 75390, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Heidelberg, Victoria, 3084, Australia

Location

Unknown Facility

Lille, 59037, France

Location

Unknown Facility

Strasbourg, 67091, France

Location

Unknown Facility

Jülich, North Rhine-Westphalia, 52425, Germany

Location

Unknown Facility

Leipzig, Saxony, 04103, Germany

Location

Unknown Facility

Toyohashi, Aichi-ken, 440-0045, Japan

Location

Unknown Facility

Toyohashi, Aichi-ken, 441-8021, Japan

Location

Unknown Facility

Toyohashi, Aichi-ken, 441-8124, Japan

Location

Unknown Facility

Isesaki, Gunma, 372-0006, Japan

Location

Unknown Facility

Hamamatsu, Shizuoka, 432-8580, Japan

Location

Unknown Facility

Itabashi-ku, Tokyo, 173-0015, Japan

Location

Related Publications (2)

• Seibyl J, Catafau AM, Barthel H, Ishii K, Rowe CC, Leverenz JB, Ghetti B, Ironside JW, Takao M, Akatsu H, Murayama S, Bullich S, Mueller A, Koglin N, Schulz-Schaeffer WJ, Hoffmann A, Sabbagh MN, Stephens AW, Sabri O. Impact of Training Method on the Robustness of the Visual Assessment of 18F-Florbetaben PET Scans: Results from a Phase-3 Study. J Nucl Med. 2016 Jun;57(6):900-6. doi: 10.2967/jnumed.115.161927. Epub 2016 Jan 28.

  PMID: 26823561 DERIVED

• Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M, Beach TG, Rowe CC, Leverenz JB, Ghetti B, Ironside JW, Catafau AM, Stephens AW, Mueller A, Koglin N, Hoffmann A, Roth K, Reininger C, Schulz-Schaeffer WJ; Florbetaben Phase 3 Study Group. Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study. Alzheimers Dement. 2015 Aug;11(8):964-74. doi: 10.1016/j.jalz.2015.02.004. Epub 2015 Mar 28.

  PMID: 25824567 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Interventions

4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Juergen Hirschfeld
• Organization: Piramal Imaging

juergen.hirschfeld@piramal.com

49 30 461 1246 15

Study Officials

• Piramal Imaging SA Study Director

  Life Molecular Imaging SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2009
• First Posted: November 26, 2009
• Study Start: November 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: December 1, 2013
• Last Updated: May 27, 2016
• Results First Posted: March 25, 2015

Record last verified: 2016-04

Locations

JP (6); DE (2); AU (1); US (8); FR (2)