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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

Primary Purpose

Alzheimer's Disease, Healthy Volunteer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
[11C]RO6924963
[11C]RO6931643
[18F]RO6958948
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Alzheimer's Disease, Healthy Volunteer

Eligibility Criteria

25 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Parexel International; Harbor Hospital Center
  • Johns Hopkins Universtiy; Radiology Dept

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Part 1: Tracer Selection

Part 2A: Test-Retest

Part 2B: Dosimetry

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan
Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan
Part 1: SUV, as Assessed by Tau PET Scan of Whole Body
Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body
Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body
Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan

Secondary Outcome Measures

Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR
Part 2A: Absolute Percentage Difference Between Test and Retest of VT
Part 2B: Effective dose (ED), as Assessed by Whole Body PET Scan
Part 2A: Absolute Percentage Difference Between Test and Retest of SUV
Percentage of Participants With Adverse Events (AEs)

Full Information

First Posted
June 17, 2014
Last Updated
December 28, 2018
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02187627
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
August 31, 2014 (Actual)
Primary Completion Date
February 29, 2016 (Actual)
Study Completion Date
February 29, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease, Healthy Volunteer

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Tracer Selection
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2A: Test-Retest
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2B: Dosimetry
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
[11C]RO6924963
Intervention Description
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6924963 injected will be </=10 micrograms (mcg), injection volume </=20 milliliters (mL). Target injected activity for [11C]RO6924963 will be 370-740 megabecquerel (MBq) [10-20 millicurie (mCi)].
Intervention Type
Drug
Intervention Name(s)
[11C]RO6931643
Intervention Description
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [11C]RO6931643 injected will be </=10 mcg, injection volume </=20 mL. Target injected activity for [11C]RO6931643 will be 370-740 MBq (10-20 mCi).
Intervention Type
Drug
Intervention Name(s)
[18F]RO6958948
Intervention Description
Radiolabeled low molecular weight compound, administered as single intravenous injection. The mass dose of [18F]RO6958948 injected will be </=10 mcg, injection volume </=20 mL. Target injected activity for [18F]RO6958948 will be 185-370 MBq (5-10 mCi). The final activity of [18F] RO6958948 will be adjusted up to 10 mCi per scan to allow sufficient counts by end of 200 minutes post radiotracer injection.
Primary Outcome Measure Information:
Title
Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan
Time Frame
Day 1 up to Day 14
Title
Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan
Time Frame
Day 1 up to Day 14
Title
Part 1: SUV, as Assessed by Tau PET Scan of Whole Body
Time Frame
Day 1 up to Day 14
Title
Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body
Time Frame
Day 1 up to Day 14
Title
Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body
Time Frame
Day 1 up to Day 14
Title
Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan
Time Frame
Day 1 up to Day 14
Secondary Outcome Measure Information:
Title
Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR
Time Frame
Days 1, 28
Title
Part 2A: Absolute Percentage Difference Between Test and Retest of VT
Time Frame
Days 1, 28
Title
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
Title
Part 2A: Absolute Percentage Difference Between Test and Retest of SUV
Time Frame
Days 1, 28
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Parexel International; Harbor Hospital Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21225
Country
United States
Facility Name
Johns Hopkins Universtiy; Radiology Dept
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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