Phase 1 Test-retest Evaluation of [18F]MNI-958 PET

Phase 1

Completed

• Conditions: Healthy Volunteers; Alzheimer Disease; Progressive Supranuclear Palsy
• Interventions: Drug: [18F]MNI-958

• Registration Number: NCT03545789
• Lead Sponsor: Invicro

Brief Summary

The overall goal of this protocol is to evaluate \[18F\]MNI-958 also known as APN-0000455 or PM-PBB3, a tau targeted radiopharmaceutical.

Detailed Description

The overall goal of this protocol is to evaluate \[18F\]MNI-958 also known as APN-0000455 or PM-PBB3, a tau targeted radiopharmaceutical. The specific objectives are:

* To measure the dynamic uptake and washout of \[18F\]MNI- 958 in brain using positron emission tomography (PET) in patients with Alzheimer's disease, Progressive Supranuclear Palsy and healthy volunteers.

* To measure blood metabolites of \[18F\]MNI-958 and perform kinetic modeling to assess its ability to measure tau protein in brain using the tracer plasma concentration or a reference region as indirect input.

* To obtain test/retest reliability of the tracer binding parameters in patients with Alzheimer's disease, Progressive Supranuclear Palsy and healthy volunteers.

* To acquire safety data following injection of \[18F\]MNI-958.

Study Timeline

• Study Start: 2018-03-12
• Study First Submitted: 2018-03-15
• Study First Submitted QC: 2018-06-01
• Study First Posted: 2018-06-04
• Status Verified: 2020-02
• Primary Completion: 2020-02-06
• Study Completion: 2020-02-06
• Last Update Submitted: 2020-02-14
• Last Update Posted: 2020-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

• Exclusion Criteria (for All subjects)

  • Current or prior history (in the last 12 months) 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 in addition to the radiation exposure expected from participation in this clinical study, 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 that may be responsible for the neurologic status of the patient such as significant evidence 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 Aβ or tau within the last 3 months.

Exclusion criteria for subjects PSP:

• Ongoing treatment with methylphenidate, modafinil, metoclopramide, alpha methyldopa, reserpine, or amphetamine derivative for subjects requiring DaTscan imaging.
• Subjects may take stable doses of bupropion, however this medication must be held for at least 12 hours prior to DaTscan imaging.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[18F]MNI-958	[18F]MNI-958	To measure blood metabolites of \[18F\]MNI-958 and perform kinetic modeling to assess its ability to measure tau protein in brain using the tracer plasma concentration or a reference region as indirect input.

Primary Outcome Measures

Name	Time	Method
Tracer uptake will be evaluated in regions of interest for analysis of regional [18F]MNI-958 binding/uptake and expressed in SUV by using established methods for normalization for 4 AD, 7 PSP, and 3 HV subjects.	1 year	Target regions of interest in the standard volume of interest (VOI) template, will be used for tracer uptake quantitation of potentially increased binding to tau pathology will correspond in particular to the cortical regions of the brain.; Descriptive statistics will be applied to describe the tau deposition by region as measured by \[18F\]MNI-958.

Trial Locations

Locations (1)

Invicro; 🇺🇸 New Haven, Connecticut, United States