Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 2 for:    NCT02187627
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02187627
Recruitment Status : Completed
First Posted : July 11, 2014
Last Update Posted : January 2, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease, Healthy Volunteer Drug: [11C]RO6924963 Drug: [11C]RO6931643 Drug: [18F]RO6958948 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : August 31, 2014
Actual Primary Completion Date : February 29, 2016
Actual Study Completion Date : February 29, 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 </=10 micrograms (mcg), injection volume </=20 milliliters (mL). Target injected activity for [11C]RO6924963 will be 370-740 megabecquerel (MBq) [10-20 millicurie (mCi)].

Drug: [11C]RO6931643
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).

Drug: [18F]RO6958948
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.

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 </=10 micrograms (mcg), injection volume </=20 milliliters (mL). Target injected activity for [11C]RO6924963 will be 370-740 megabecquerel (MBq) [10-20 millicurie (mCi)].

Drug: [11C]RO6931643
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).

Drug: [18F]RO6958948
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.

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 </=10 micrograms (mcg), injection volume </=20 milliliters (mL). Target injected activity for [11C]RO6924963 will be 370-740 megabecquerel (MBq) [10-20 millicurie (mCi)].

Drug: [11C]RO6931643
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).

Drug: [18F]RO6958948
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 Measures :
  1. Part 1: Standard Uptake Value (SUV), as Assessed by Tau PET Brain Scan [ Time Frame: Day 1 up to Day 14 ]
  2. Part 1: Standard Uptake Value Ratio (SUVR), as Assessed by Tau PET Brain Scan [ Time Frame: Day 1 up to Day 14 ]
  3. Part 1: SUV, as Assessed by Tau PET Scan of Whole Body [ Time Frame: Day 1 up to Day 14 ]
  4. Part 1: SUVR, as Assessed by Tau PET Scan of Whole Body [ Time Frame: Day 1 up to Day 14 ]
  5. Mean Residence Times for Each Organ, as Assessed by Tau PET Scan of Whole Body [ Time Frame: Day 1 up to Day 14 ]
  6. Part 1: Distribution Volume (VT), as Assessed by Tau PET Brain Scan [ Time Frame: Day 1 up to Day 14 ]

Secondary Outcome Measures :
  1. Part 2A: Absolute Percentage Difference Between Test and Retest of SUVR [ Time Frame: Days 1, 28 ]
  2. Part 2A: Absolute Percentage Difference Between Test and Retest of VT [ Time Frame: Days 1, 28 ]
  3. 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 ]
  4. Part 2A: Absolute Percentage Difference Between Test and Retest of SUV [ Time Frame: Days 1, 28 ]
  5. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   25 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02187627


Locations
Layout table for location information
United States, Maryland
Parexel International; Harbor Hospital Center
Baltimore, Maryland, United States, 21225
Johns Hopkins Universtiy; Radiology Dept
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02187627    
Other Study ID Numbers: BP29409
First Posted: July 11, 2014    Key Record Dates
Last Update Posted: January 2, 2019
Last Verified: December 2018
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders