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
Phase 1
Completed
- Conditions
- Alzheimer's Disease, Healthy Volunteer
- Interventions
- Drug: [11C]RO6924963Drug: [11C]RO6931643Drug: [18F]RO6958948
- Registration Number
- NCT02187627
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
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
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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
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2A: Test-Retest [18F]RO6958948 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. Part 1: Tracer Selection [18F]RO6958948 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. Part 2A: Test-Retest [11C]RO6931643 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. Part 2B: Dosimetry [18F]RO6958948 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. Part 1: Tracer Selection [11C]RO6924963 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. Part 1: Tracer Selection [11C]RO6931643 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. Part 2A: Test-Retest [11C]RO6924963 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. Part 2B: Dosimetry [11C]RO6931643 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. Part 2B: Dosimetry [11C]RO6924963 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.
- Primary Outcome Measures
Name Time Method Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan Day 1 up to Day 14 Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan Day 1 up to Day 14 Part 1: SUV, as Assessed by Tau PET Scan of Whole Body Day 1 up to Day 14 Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body Day 1 up to Day 14 Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body Day 1 up to Day 14 Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan Day 1 up to Day 14
- Secondary Outcome Measures
Name Time Method Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR Days 1, 28 Part 2A: Absolute Percentage Difference Between Test and Retest of VT Days 1, 28 Part 2B: Effective dose (ED), as Assessed by Whole Body PET Scan 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 Days 1, 28 Percentage of Participants With Adverse Events (AEs) Part 1: Day 1 up to Day 28, Part 2a: Day 1 up to Day 42, Part 2b: Day 1 up to Day 15
Trial Locations
- Locations (2)
Johns Hopkins Universtiy; Radiology Dept
🇺🇸Baltimore, Maryland, United States
Parexel International; Harbor Hospital Center
🇺🇸Baltimore, Maryland, United States