Assessment of [18F]MNI-1054 as a Marker for LSD1

An Open-label, Brain Positron Emission Tomography, Phase 0 Study of [18F]MNI-1054 as a Marker for LSD1 in Healthy Subjects

The primary objective of this protocol is to evaluate [18F]MNI-1054 as a Lysine-specific histone demethylase 1A (LSD1) enzyme targeted radiopharmaceutical.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers (HV)
• Intervention / Treatment: Drug: [18F]MNI-1054

Detailed Description

The primary objective of this protocol is to evaluate [18F]MNI-1054 as a Lysine-specific histone demethylase 1A (LSD1) enzyme targeted radiopharmaceutical. The specific objectives are:

• To measure the dynamic uptake and washout of [18F]MNI-1054 in brain using positron emission tomography (PET) in healthy volunteers.
• To measure blood metabolites of [18F]MNI-1054 in the healthy volunteers and to perform invasive as well as non-invasive modeling to assess its ability to measure LSD1 in the brain.
• To acquire safety data following injection of [18F]MNI-1054
• Evaluation of [18F]MNI-1054 PET reliability (test/retest) of the tracer parameters in healthy volunteers.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Invicro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Understand the study procedures and agree to participate by providing written informed consent.
• Are willing and able to comply with all study procedures and restrictions.
• Are males or females > 18 years of age and < 50 years of age.
• Are in good health as determined by the investigator based on clinical evaluations including past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening and prior to the first dose of study drug.
• Are a current nonsmoker who has not used tobacco- or nicotine-containing products (eg, nicotine patch) for at least 6 months prior to the first dose of study drug or first invasive procedure.
• Are a female subject of nonchildbearing potential, 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 (i.e. 12 consecutive months with no menses without an alternative medical cause) or, if they are of child-bearing potential, must commit to use two methods of contraception, one of which is a barrier method for the duration of the study.
• Are a male subject who is sterile or agrees to use an appropriate method of contraception, including a condom with or without spermicidal cream or jelly, from the first dose of study drug until 30 days after the last dose of study drug. No restrictions are required for a vasectomized male subject provided the subject is at least 1-year postbilateral vasectomy procedure prior to the first dose of study drug. A male subject whose vasectomy procedure was performed less than 1 year prior to the first dose of study drug must follow the same restrictions as a nonvasectomized man. Appropriate documentation of surgical procedure should be provided.
• Male subjects must not donate sperm for the study duration and for 30 days following the last dose of study drug.

Exclusion Criteria:

• Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing. If needed (i.e. an incidental and limited need), acetaminophen is acceptable, but must be documented as a concomitant medication / significant non-drug therapy.
• Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
• 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 millisievert (mSv), which would be above the acceptable annual limit established by the US Federal Guidelines.
• Has a known hypersensitivity to any component of the formulation of [18F]MNI-1054 or related compounds.
• Major surgery, or donation or loss of 400 mL or more of blood within four (4) weeks prior to initial dosing, or longer if required by local regulation.
• Have a history or presence of any significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or neurological disorders which, in the opinion of the investigator, are capable of altering the absorption, metabolism, or elimination of drugs or posing a health risk to participate in the study.
• The subject has a history of cancer (malignancy).
• Have clinically significant findings on laboratory evaluations.
• Have clinically significant findings on ECG evaluation.
• History of immunodeficiency diseases, including a positive HIV test result.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result.
• History of drug or alcohol abuse within the 12 months prior to screening, or evidence of such abuse as indicated by the laboratory assays (i.e. positive drug or alcohol screen) conducted during the screening.
• The subject has a history of alcohol consumption exceeding 2 standard drinks per day on average (1 glass is approximately equivalent to the following: beer [354 mL/12 oz], wine [118 mL/4 oz], or distilled spirits [29.5 mL/1 oz] per day).
• The subject consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
• Positive pregnancy test result using serum beta-human chorionic gonadotropin (HCG), if female.
• Women who are lactating and breastfeeding.
• The subject is an employee of the sponsor or trial site or immediate family member (e.g., spouse, parent, child, sibling) of the sponsor or trial site.
• MRI exclusion criteria include: Findings of infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with central nervous system (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]MNI-1054; To measure blood metabolites, dynamic uptake, and washout of [18F]MNI-1054 in brain using positron emission tomography (PET) in healthy volunteers.	Drug: [18F]MNI-1054; Healthy volunteers recruited for the study will undergo a [18F]MNI-1054 PET scan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average and standard deviation across subjects of the variability ((test - retest) / average(test, retest) ) as well as the intraclass correlation (ICC).	Adequacy of the initial scan brain uptake for completion of a retest scan will be based on maximum Standard Uptake value (SUV), where a maximum SUV > 1.5 will be considered sufficient, possibly sufficient between 1.0 and 1.5, and insufficient below 1.0.	1 year

Collaborators and Investigators

• Sponsor: Invicro

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2018
• Primary Completion (Actual): May 2, 2019
• Study Completion (Actual): May 2, 2019

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 2, 2018
• First Posted (Actual): October 4, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2019
• Last Update Submitted That Met QC Criteria: May 22, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: HV
• Other Study ID Numbers: [18F]MNI-1054

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No