Evaluation of [18F]MNI-952 as a Potential PET Radioligand for Imaging Tau Protein in the Brain

• ClinicalTrials.gov Identifier: NCT03080051
• Recruitment Status: Completed
• First Posted: March 15, 2017
• Last Update Posted: October 6, 2017
• Sponsor: Molecular NeuroImaging
• Information provided by (Responsible Party): Molecular NeuroImaging

Study Description

Brief Summary:

The overall goal of this imaging trial is to evaluate [18F]MNI-952 (also known as [18F]UCB-K), a tau targeted PET radioligand.

Condition or disease	Intervention/treatment	Phase
Progressive Supranuclear Palsy; Alzheimer Disease; Healthy Volunteers	Drug: [18F]MNI-952; Drug: [18F]Florbetapir	Early Phase 1

Detailed Description:

The overall goal of this imaging trial is to evaluate [18F]MNI-952 (also known as [18F]UCB-K), a tau targeted PET radioligand.

• To characterize [18F]MNI-952, a PET radioligand for imaging tau.
• To visually and quantitatively assess brain uptake and pharmacokinetics of [18F]MNI-952, a PET imaging marker for tau pathology in individuals with Progressive Supranuclear Palsy (PSP) or Alzheimer's disease (AD) and compare with healthy volunteers (HV).
• To evaluate the safety of a single injection of [18F]MNI-952.
• To compare the distribution of tau (using [18F]MNI-952) and Aâ (using florbetapir) in AD subjects.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Phase 0 Evaluation of [18F]MNI-952 as a Potential PET Radioligand for Imaging Tau Protein in the Brain of Patients With Progressive Supranuclear Palsy or Alzheimer's Disease Compared to Healthy Volunteers
• Study Start Date: August 2016
• Actual Primary Completion Date: March 6, 2017
• Actual Study Completion Date: March 6, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: [18F]MNI-952; To evaluate [18F]MNI-952 (also known as [18F]UCB-K), a tau targeted PET radioligand.	Drug: [18F]MNI-952; Subjects will undergo PET imaging using [18F]MNI-952, a PET radioligand for imaging tau.; Other Name: [18F]UCB-K; Drug: [18F]Florbetapir; Subjects with Alzheimer's disease will receive a [18F]florbetapir scan to compare distribution of tau in the brain compared to that of [18F]MNI-952.

Outcome Measures

Primary Outcome Measures :

1. Tracer uptake will be evaluated in regions of interest for analysis of regional [18F]MNI-952 binding/uptake and expressed in SUV by using established methods for normalization for 2 PSP, 2 AD, and 2 HV subjects. [ Time Frame: 1 year ]
   Descriptive statistics will be applied to describe the tau deposition by region as measured by [18F]MNI-952.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed.
• Female subjects must be documented by medical records or physician's note to be either surgically sterile (by means of hysterectomy, bilateral oophorectomy, or tubal ligation) or post-menopausal for at least 1 year or, if they are of child-bearing potential, must commit to use a barrier contraception method for the duration of the study.
• Male subjects and their partners of childbearing potential must commit to the use of two methods of contraception, one of which is a barrier method for male subjects for the study duration.
• Male subjects must not donate sperm for study duration and for 90 days following participation.
• Willing and able to cooperate with study procedures

Inclusion Criteria for healthy volunteer subjects:

• Males and females aged <55 years. Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the [18F]MNI-952 imaging visit.
• No neurologic impairment as judged by the investigator
• No family history of Alzheimer's disease or neurological disease associated with dementia
• Have a CDR score=0

Inclusion Criteria for subjects with a diagnosis of probable Alzheimer's disease (AD):

• Males and females aged between 50 and 90 years.
• Have probable Alzheimer's disease, based on the NINCDS/ADRDA and DSM-IV criteria.
• Have a CDR score of 0.5 or greater at screening.
• Have an MMSE score ≤ 28.
• Have a screening [18F]florbetapir PET imaging demonstrating amyloid binding based on qualitative (visual read)
• A brain MRI that supports a diagnosis of AD, with no evidence of focal disease to account for dementia or MRI exclusion criteria.
• Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 30 days before the screening visit
• The subject has an appropriate caregiver capable of accompanying subject, if necessary.
• Signed and dated written informed consent obtained from the subject and/or the subject's legally authorized representative or caregiver (if applicable).

Inclusion Criteria for subjects with a diagnosis of probable Progressive Supranuclear Palsy (PSP):

• Males and females aged 50 to 90 years.
• Has a clinical diagnosis of PSP based on the NINDS and Society for PSP criteria (Litvan, et al 1996).
• Have screening DaTSCAN SPECT imaging demonstrating evidence of dopamine transporter deficit based on qualitative (visual) read.
• A brain MRI that supports a diagnosis of PSP, with no evidence of focal disease or MRI exclusion criteria.
• Medications taken for symptomatic treatment of PSP must be maintained on a stable dosage regimen for at least 30 days before screening visit.
• The subject has an appropriate caregiver capable of accompanying subject, if necessary.
• Signed and dated written informed consent obtained from the subject and the subject's legally authorized representative or caregiver (if applicable).

Exclusion Criteria:

• Current or prior history of any alcohol or drug abuse.
• Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness.
• Subject has received an investigational drug or device within 30 days of screening
• Prior participation in other research protocols or clinical care in the last year such that radiation exposure exceeds the effective dose of 50 mSv, which would be above the acceptable annual limit established by the US Federal Guidelines.
• Pregnancy, lactating or breastfeeding.
• Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Unsuitable veins for repeated venipuncture.
• MRI exclusion criteria include: Findings of cerebrovascular disease (more than two lacunar infarcts, any territorial infarct >1cm3, or deep white matter abnormality corresponding to an overall Fazekas scale of 3 with at least one confluent hyperintense lesion on the FLAIR sequence that is ≥20 mm in any dimension), infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with CNS disease.
• Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI.

Exclusion criteria for subjects with AD:

• Has received treatment that targeted amyloid-β or tau within the last 3 months.

Contacts and Locations

Locations

United States, Connecticut

Molecular NeuroImaging, LLC

New Haven, Connecticut, United States, 06510

Sponsors and Collaborators

Molecular NeuroImaging

Investigators

• Principal Investigator: Jennifer Madonia, PA-C; Molecular NeuroImaging

More Information

Publications:

Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul;47(1):1-9. Review.

• Responsible Party: Molecular NeuroImaging
• ClinicalTrials.gov Identifier: NCT03080051
• Other Study ID Numbers: [18F]MNI-952
• First Posted: March 15, 2017
• Last Update Posted: October 6, 2017
• Last Verified: October 2017

Keywords provided by Molecular NeuroImaging:

PSP; AD; HV

Additional relevant MeSH terms:

Alzheimer Disease; Supranuclear Palsy, Progressive; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Basal Ganglia Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases