Evaluation of [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948 as Tracers for Positron Emission Tomography (PET) Imaging of Tau in Healthy and Alzheimer's Disease (AD) Participants

December 28, 2018 updated by: Hoffmann-La Roche

Evaluation of [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948 as Tracers for Tau Imaging With Positron Emission Tomography in Healthy Control Subjects and Subjects With Alzheimer's Disease

This study is designed to obtain basic information on three PET imaging tracers developed to detect tau pathology in the brain. In this study, healthy control participants and participants with AD will be studied. Information collected will include brain and plasma kinetics, tissue distribution (in the brain), radiation dosimetry, and test-retest variability of the signal in the brain. The study will consist of Part 1, Part 2A, and Part 2B. During Part 1, imaging data will be assessed on an ongoing basis and based on data, one tracer will be prioritized over the other two tracers. The tracer selected will be further investigated in Part 2A and Part 2B.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21225
        • Parexel International; Harbor Hospital Center
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Universtiy; Radiology Dept

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion Criteria for All Participants

  • Agreement to use highly effective contraception measures
  • If participants are on any concomitant medication, the indication and dosage of these medicines should be stable for at least 4 weeks prior to study start with the expectation that no relevant changes in use or dose will occur throughout the study
  • Body mass index (BMI) between 18 and 32 kilograms per square meter (kg/m^2)
  • Weight less than or equal to (</=) 300 pounds (lb)

Inclusion Criteria for Healthy Control Participants

  • Healthy "young" control participants aged 25-40 years or healthy "elderly" control participants aged greater than or equal to (>/=) 50 years
  • Normal cognitive function, including a normal Mini Mental State Examination (MMSE) score as judged by the investigator
  • Healthy control participants who participate in Part 2B: must be less than (<) 195 centimeter (cm) (6 feet, 5 inches) tall in order to accommodate the whole body scanning

Inclusion Criteria for Participants with a Diagnosis of Probable AD

  • Diagnosis of probable AD, according to the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria
  • Participants aged >/= 50 years
  • A study partner able to accompany the participant to all visits and answer questions about the participant
  • MMSE score between 16 and 26, inclusive

Exclusion Criteria:

Exclusion Criteria for All Participants

  • History or presence of a neurological diagnosis other than AD that may influence the outcome or analysis of the scan results; examples include but are not limited to stroke, traumatic brain injury, space occupying lesions, non-Alzheimer's tauopathies, and Parkinson's disease
  • Participants with a medical history that includes known autosomal dominant AD mutations in amyloid precursor protein (APP) or presenilin (PS1, PS2) or mutations in genes that cause other types of autosomal dominant familial dementia
  • History or presence of any clinically relevant hematological, hepatic, respiratory, cardiovascular, renal, metabolic, endocrine, or central nervous system disease or other medical conditions that are not well controlled, may put the participant at risk, could interfere with the objectives of the study, or make the participant unsuitable for participation in the study for any other reason in the opinion of the principal investigator
  • Clinically relevant pathological findings in physical examination, electrocardiogram, or laboratory values at the screening assessment that could interfere with the objectives of the study
  • Known history of clinically significant infectious disease including acquired immunodeficiency syndrome (AIDS) or serological indication of acute/chronic hepatitis B or C or human immunodeficiency virus infection
  • Pregnancy or lactation
  • Unsuitable veins for repeated venipuncture
  • Current symptoms of allergy and/or severe allergy to drugs in medical history
  • Alcohol consumption that averages >3 drinks daily or regular smoker (>10 cigarettes, >3 pipefuls, or >3 cigars per day)
  • Coffee (or tea) consumption >10 cups per day or methylxanthine-containing drinks >1.5 liters per day (L/day)
  • Have received an investigational medication within the last 3 months or 5 times (x) the elimination half-life, whichever is longer, prior to Day 1 (i.e., enrollment)

Exclusion Criteria Related to Trial Procedures

  • Presence of pacemakers; aneurysm clips; artificial heart valves; ear implants; foreign metal objects in the eyes, skin, or body, or any other circumstance (e.g. claustrophobia) that would contraindicate a magnetic resonance imaging (MRI) scan
  • For participants of Part 1 and Part 2A, any contraindications to arterial cannulation

Exclusion Criterion for Participants with Probable Alzheimer's Disease

  • Has received treatment that targeted amyloid-beta or tau within the last 24 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1: Tracer Selection
Participants will receive a single dose of one tracer on one occasion and a single dose of a different tracer after 7 to 14 days and will be followed for 7 to 14 days for safety. At the end of Part 1, one tracer with the best performance will be selected for further study in Part 2.
Drug: [11C]RO6924963
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6924963 injected will be
Drug: [11C]RO6931643
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6931643 injected will be
Drug: [18F]RO6958948
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [18F]RO6958948 injected will be
Experimental: Part 2A: Test-Retest
Participants will receive a single dose of selected tracer from Part 1 on one occasion and then same tracer will be administered after 6 weeks. Participants will be followed for 7 to 14 days after last PET tracer administration for safety.
Drug: [11C]RO6924963
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6924963 injected will be
Drug: [11C]RO6931643
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6931643 injected will be
Drug: [18F]RO6958948
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [18F]RO6958948 injected will be
Experimental: Part 2B: Dosimetry
Participants will receive a single dose of selected tracer from Part 1 and will be followed for 7 to 14 days for evaluation of radiation dosimetry.
Drug: [11C]RO6924963
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6924963 injected will be
Drug: [11C]RO6931643
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6931643 injected will be
Drug: [18F]RO6958948
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [18F]RO6958948 injected will be

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan
Time Frame: Day 1 up to Day 14
Day 1 up to Day 14
Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan
Time Frame: Day 1 up to Day 14
Day 1 up to Day 14
Part 1: SUV, as Assessed by Tau PET Scan of Whole Body
Time Frame: Day 1 up to Day 14
Day 1 up to Day 14
Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body
Time Frame: Day 1 up to Day 14
Day 1 up to Day 14
Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body
Time Frame: Day 1 up to Day 14
Day 1 up to Day 14
Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan
Time Frame: Day 1 up to Day 14
Day 1 up to Day 14

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR
Time Frame: Days 1, 28
Days 1, 28
Part 2A: Absolute Percentage Difference Between Test and Retest of VT
Time Frame: Days 1, 28
Days 1, 28
Part 2B: Effective dose (ED), as Assessed by Whole Body PET Scan
Time Frame: From the time of tracer injection on Day 1 up to 120 minutes post injection
From the time of tracer injection on Day 1 up to 120 minutes post injection
Part 2A: Absolute Percentage Difference Between Test and Retest of SUV
Time Frame: Days 1, 28
Days 1, 28
Percentage of Participants With Adverse Events (AEs)
Time Frame: Part 1: Day 1 up to Day 28, Part 2a: Day 1 up to Day 42, Part 2b: Day 1 up to Day 15
Part 1: Day 1 up to Day 28, Part 2a: Day 1 up to Day 42, Part 2b: Day 1 up to Day 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 31, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 29, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 29, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 17, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 11, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 2, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 28, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BP29409

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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