AzTrials
AzTrials

Alzheimer DiseasePhase 2NCT00750282

Phase II Study of Florbetaben (BAY 94-9172) PET Imaging for Detection/Exclusion of Cerebral β-amyloid in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers

A Phase 2 study testing Florbetaben (BAY94-9172) in people with Alzheimer Disease and Amyloid Beta-Protein, run by Lantheus Biosciences Ltd. at 23 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK 6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque (amyloid beta) with positron emission tomography (PET). Read more about this study

Who is it for?
Ages 55 years and older
Conditions the study is for
Alzheimer Disease, Amyloid Beta-Protein
What is being tested?
Florbetaben (BAY94-9172)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
422 participants
Where
23 sitesin 5 countries
Study dates
Aug 2008to Nov 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each subject / Healthy volunteer (HV) who meets the following criteria will be eligible for enrollment into the study:
  • Is a man or woman and is > 55 of age, whereby females must be without childbearing potential (confirmed by either: age >/= 60; or history of hysterectomy, or last spontaneous bleeding at least 2 years prior to the study start)
  • Has at least 6 years of education
  • Is able to provide informed consent, understand the information provided on the purpose and conduct of the trial and to comply with study procedures
  • Possesses a general health that permits adequate compliance with all study procedures
  • The subject, or the subject and caregiver (for probable AD patients) will be compliant and have a high probability of completing the study
Show all 13Show fewer
  • Informed consent has been signed and dated (with time) by the subject and/or the subject's caregiver (for probable AD patients)
  • Has no evidence of cognitive impairment
  • Has MRI brain scan that has been judged as "normal" (age- appropriate)
  • Presents with positive assessment for dementia of Alzheimer's type
  • Does not fulfill the criteria Dementia with Lewy Bodies (DLB) or Vascular Dementia (VaD)
  • MRI brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease
  • Has a caregiver that is willing and able to attend all study visits and perform the psychometric tests requiring the presence of a caregiver

Who cannot join

  • Has any contraindication to MRI examination scan
  • Is scheduled for surgery and/or another invasive procedure within the time period of up to 24 hours following IMP application
  • Is allergic to the IMP or any of its constituents and/or has a history of severe allergic reactions to drugs or allergens (e.g. patients / volunteers with allergic asthma)
  • is critically ill and/or medically unstable and whose clinical course during the observation period is unpredictable
  • Has a history of exposure to any radiation >15 milli Sieverts (mSv)/year (e.g. occupational or radiation therapy)
  • Is receiving drug therapy or other treatment that is known to lead to greatly fluctuating values of the hematological or chemical laboratory parameters or to severe side effects (e.g. chemotherapy)
Show all 13Show fewer
  • 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 any radiopharmaceutical
  • Has a brain tumor or other intracranial lesion, a disturbance of cerebro-spinal fluid (CSF) circulation (e.g., normal pressure hydrocephalus) and/or a history of head trauma or brain surgery
  • Has an inflammatory or infectious central nervous system (CNS) disease, e.g. multiple sclerosis, HIV, syphilis, or Creutzfeldt-Jacob disease
  • Has a history, physical, laboratory or imaging findings indicative of a neurological or psychiatric illness
  • Has another disease that can cause disturbance of brain function (e.g. vitamin B12 or folic acid deficiency, disturbed thyroid function)
  • Has a history of alcohol or drug abuse
  • Has history of severe persistent depression

Trial locations and contacts

23 sites in 5 countries.

23 sites in 5 countries

Germany9 sites

  • Study site

    Berlin, State of Berlin, 13125

  • Study site

    Dresden, Saxony, 01307

  • Study site

    Erlangen, Bavaria, 91054

  • Study site

    Essen, North Rhine-Westphalia, 45122

  • Study site

    Jülich, North Rhine-Westphalia, 52425

  • Study site

    Leipzig, Saxony, 04103

  • Study site

    München, Bavaria, 81377

  • Study site

    München, Bavaria, 81675

  • Study site

    Münster, North Rhine-Westphalia, 48149

Other trials in Germany

United States7 sites

  • Study site

    New Haven, Connecticut, 06510

  • Study site

    New York, New York, 10016

  • Study site

    New York, New York, 10032

  • Study site

    Providence, Rhode Island, 02906

  • Study site

    Stanford, California, 94305

  • Study site

    Sun City, Arizona, 85351

  • Study site

    The Bronx, New York, 10461

Other trials in United States

Australia3 sites

  • Study site

    Adelaide, South Australia, 5000

  • Study site

    Heidelberg, Victoria, 3084

  • Study site

    Westmead, New South Wales, 2145

Other trials in Australia

Japan3 sites

  • Study site

    Bunkyo-ku, Tokyo, 113-8603

  • Study site

    Kobe, Hyōgo, 650-0017

  • Study site

    Kobe, Hyōgo, 650-0047

Other trials in Japan

Switzerland1 site

  • Study site

    Zurich, Canton of Zurich, 8091

Other trials in Switzerland

About this study

Official title: An Open-label, Non-randomized, Multi-center Study to Optimize Image Assessment and Evaluate the Efficacy and Safety of BAY 94-9172 (ZK 6013443) Positron Emission Tomography (PET) for Detection/Exclusion of Cerebral Amyloid Beta in Patients With Probable Alzheimer's Disease Compared to Healthy Volunteers

The aim of this study is to evaluate the efficacy, safety of a single dose of BAY 94-9172 (ZK 6013443) as an investigational medicinal product (IMP) in detecting cerebral protein-plaque (amyloid beta) with positron emission tomography (PET). IMP binds to amyloidal beta protein accumulating in brain tissue already from early stages of Alzheimer's disease (AD). IMP is therefore a potential tracer to be used for detecting amyloid plaques. For each subject it is required to visit the study centre during the screening phase, on the PET imaging day and for 1 follow-up visit on the next day. A telephone call for safety follow-up will be performed 7 days after IMP administration. During the screening phase the subject's medical, neurological and surgical history, specific laboratory tests related to AD, MRI of the brain and certain neuro-psychiatric tests will be performed. Clinical safety measures (physical examinations, vital signs, electrocardiogram (ECG) and laboratory tests) will be performed on the PET imaging day before IMP injection and monitored during and after two PET imaging sessions. Clinical safety measures will be performed again on the follow-up visit next day. The results of PET imaging with IMP will be compared between probable AD patients and healthy volunteers (HV). The clinical diagnosis is based on international validated and accepted criteria and established after comprehensive clinical and neuro-psychiatric examinations

Being tested
Florbetaben (BAY94-9172)
Keywords
Alzheimer Disease, Amyloid beta-Protein
Medical subject headings
Alzheimer Disease, Plaque, Amyloid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Florbetaben (BAY94-9172)Drug

    Healthy volunteers and patients with probable Alzheimer's disease receiving single injection of investigational medicinal product BAY 94-9172 followed by subsequent PET imaging sessions

Study groups in NCT00750282
Study groupRoleWhat they receive
Florbetaben (BAY94-9172)ExperimentalNot described
Receives: Drug: Florbetaben (BAY94-9172)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth

    Part A: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan which was considered a match for specificity. Standard of truth was the onsite clinical diagnosis.

    Two Beta-Amyloid Plaque Load (BAPL) algorithms for assessing the normality/abnormality of beta-amyloid plaque load in the brain scans were used.

    Using algorithm A (Majority Read), a brain scan of a subject with a BAPL score of "1" (without beta-amyloid plaque load) or "2" (with minor beta-amyloid plaque load) was considered normal and a BAPL score of "3" (with significant beta-amyloid plaque load) was considered abnormal.

    Using algorithm B (Average), a brain scan of a subject with a BAPL score of "1" was considered normal and a brain scan with a BAPL score of "2" or "3" was considered abnormal. Algorithm B was used in Part B and in the final

    Measured: 90 - 110 min after investigational medical product (IMP) injection

  2. Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part B Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth.

    Part B: For the calculation of sensitivity/specificity, a patient with probable AD was expected to have a positive florbetaben PET scan, ie,abnormal scan (BAPL scores "2" or "3") which was considered a match for sensitivity. A HV was expected to have a negative florbetaben PET scan, ie,normal scan (BAPL score "1") which was considered a match for specificity.

    The clinical diagnosis was established by an independent consensus panel (CP) of experts in dementia.

    Two independent sets of PET data reads were performed. The first set was performed by a panel of three readers who received live, instructor-led training on the visual assessment procedure. The second set was performed by a panel of five separate readers who were trained on the visual assessment procedure with electronic media.

    Measured: 90 - 110 min after IMP injection

Secondary outcomes (3)

  1. Sensitivity and Specificity for All Participants Using Two Additional Imaging Windows for the Visual Assessment

    PET scans from two additional imaging windows (45-60 min and 110-130 min) were visually assessed

    Measured: 45 - 60 min and 110 - 130 min after IMP injection

  2. Kappa Coefficient as a Measure of Agreement Between Readers Concerning the Visual Assessment of Abnormality of the Brain Scan (Based on BAPL Score)

    The agreement between 3 blinded readers concerning the visual assessment of abnormality of the brain scan (based on BAPL score) was measured by the kappa coefficient. Kappa values close to 1.0 indicate a high agreement while values close to 0 indicate random agreement.

    Measured: 45-60 min, 90-110 min, 110-130 min

  3. Standard Uptake Value Ratios for Florbetaben Signal

    The Standard Uptake Value Ratios for florbetaben signal in the frontal cortex, lateral temporal cortex, parietal cortex, anterior cingulate, posterior cingulate cortex, occipital cortex, and cerebellum (white matter) were determined as a quantitative measure of tracer uptake. The SUV is defined as the ratio of (1) the tissue radioactivity concentration c (in MBq/kg) at time point t, and (2) the injected activity (in MBq, extrapolated to the same time t) divided by the body weight (in kg). These SUV numbers from regions of interest were then used to derive SUV ratios (SUVR) using the SUV from the cerebellar cortex as reference.)

    Measured: 90-110 min post injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionNov 2010
  4. Study completionNov 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
422 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00750282
Sponsor's protocol ID
311741
Other IDs
2007-002256-42, 311741
Status last verified
Jul 2014
First submitted
9 Sep 2008
Last updated
24 Jul 2014
Data monitoring committee
No

Publications

  • Barthel H, Gertz HJ, Dresel S, Peters O, Bartenstein P, Buerger K, Hiemeyer F, Wittemer-Rump SM, Seibyl J, Reininger C, Sabri O; Florbetaben Study Group. Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011 May;10(5):424-35. doi: 10.1016/S1474-4422(11)70077-1. Epub 2011 Apr 8.

    PubMed 21481640

  • Bullich S, Roe-Vellve N, Marquie M, Landau SM, Barthel H, Villemagne VL, Sanabria A, Tartari JP, Sotolongo-Grau O, Dore V, Koglin N, Muller A, Perrotin A, Jovalekic A, De Santi S, Tarraga L, Stephens AW, Rowe CC, Sabri O, Seibyl JP, Boada M. Early detection of amyloid load using 18F-florbetaben PET. Alzheimers Res Ther. 2021 Mar 27;13(1):67. doi: 10.1186/s13195-021-00807-6.

    PubMed 33773598

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Florbetaben (BAY94-9172) in people with Alzheimer Disease and Amyloid Beta-Protein, run by Lantheus Biosciences Ltd. at 23 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Germany, United States, Australia, Japan, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Specificity and Sensitivity of Florbetaben PET Scans Obtained in Part A Using Two Separate Algorithms and the Onsite Clinical Diagnosis as the Standard of Truth (time frame: 90 - 110 min after investigational medical product (IMP) injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00750282, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in