A Multiple Dose Study of the Safety and Pharmacokinetics of NTRX-07

A Multiple Ascending Dose, Phase 1, Double-Blind, Study to Investigate the Safety and Pharmacokinetics of NTRX-07 in Healthy Volunteers and Patients With Early Alzheimer's Disease (AD), With an Exploratory Fed-Fasted Assessment

This is a Phase 1, Randomized, Placebo-Controlled, Modified Parallel Design Multiple Ascending Dose Study of NTRX 07 to Assess Safety and Tolerability and Pharmacokinetics in Adult Healthy Volunteers and Subjects with MCI or Early AD. In addition, an exploratory study of the effect of a high fat meal was conducted.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: NTRX-07

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Kistarcsa, Hungary
    • CRU Early Phase Unit Kistarcsa
• United States
  • Ohio
    • Gates Mills, Ohio, United States, 44040
      • NeuroTherapia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must be 45 80 years of age inclusive, at the time of signing the informed consent
• Cohorts A-C participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

• Cohort D - AD as characterized by the following clinical, cognitive, and functional criteria.

  • Diagnosis of a clinical syndrome of cognitive impairment consistent with prodromal AD per International Working Group (IWG) diagnostic criteria or mild AD per National Institute on Aging - Alzheimer's Association (NIAA-AA) diagnostic criteria
  • Self or informant report of memory decline
  • Mini-Mental State Examination (MMSE) scores between 18-27 inclusive within the last 4 months
  • Objective memory loss by education-adjusted Wechsler Memory Scale Logical Memory II consistent with mild cognitive impairment with Alzheimer's disease (MCI AD) or mild AD
  • Absence of significant levels of impairment in other cognitive assessments
• Cohort D - Previous brain imaging study, such as magnetic resonance imaging (MRI) and/or computed tomography (CT), consistent with a diagnosis of probably AD without any other clinically significant co-morbid pathologies within 12 months prior to the Screening Visit. If there has been a significant change in clinical status suggestive of stroke or other possible central neurological disease with onset between the time of the last MRI or CT and the Screening evaluation, the scan should be repeated during Screening procedures if considered appropriate by the Investigator OR Screening cerebrospinal fluid (CSF) results consistent with the presence of amyloid pathology.
• Cohort D - No active depression and a Geriatric Depression Score of <6.
• Cohort D - Absence of other (non-AD) types of dementia.
• Cohort D - Participants previously enrolled in an AD clinical trial involving a disease modifying or symptomatic therapeutic agent may enroll in this study if treatment with the symptomatic therapeutic agent ended more than 6 months before the first dose of NTRX 07-SDD in this study.
• Body weight within 55 110 kg and body mass index (BMI) within the range 18 35 kg/m2 (inclusive)
• Male or Female
• The effects of NTRX 07 on pregnancy, fetal development, and excretion in breast milk is currently unknown. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the subject information sheet, informed consent form (ICF) and in this protocol.

Exclusion Criteria:

• Reported history or presence of clinically significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data. Participants with stable well controlled conditions may be accepted on review with the Investigator and sponsor.
• Reported current or chronic history of clinically significant liver disease. This includes but is not limited to hepatitis virus infections, drug- or alcohol-related liver disease, nonalcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease considered clinically significant by the investigator.
• Reported hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Cohort D - Reside in a nursing home or assisted care facility with need for direct continuous medical care and nursing supervision. Participant may reside in such facilities provided continuous direct medical care is not required.
• Cohort D - Unable to provide for self for basic activities of daily living.
• Cohort D - Major structural brain disease by reported history or chart review (eg, ischemic infarcts, subdural hematoma, hemorrhage, hydrocephalus, brain tumors, multiple subcortical ischemic lesions, or a single lesion in a critical region eg, thalamus, hippocampus).
• Any other reported history of central nervous system (CNS) trauma (eg, contusion), or infections that affect brain function (eg, human immunodeficiency virus [HIV], syphilis), history of seizures
• Diagnosis of schizophrenia
• Any reported history from patient, family, or on supplied chart review or current suicide risk
• Cohort D - Diagnosis of a dementia-related CNS disease other than AD (eg, Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus)
• Reported past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing. Specific medications listed in Section Concomittant Therapy may be allowed.
• Reported treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
• Alanine transaminase (ALT) or aspartate transaminase (AST) >1.5 x upper limit of normal (ULN)
• Total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if total bilirubin is fractionated and direct bilirubin <35%)
• QTcF >450 msec for male participants or >470 msec for female participants
• Positive prestudy drug/alcohol screen
• Positive HIV antibody test
• Clinical laboratory findings outside the normal range and determined by the investigator or medical monitor to be clinically significant.
• Clinically significant abnormalities on screening EEG which may indicate an increased risk of seizure liability.
• Reported sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study
• Reported regular use of known drugs of abuse within the past 3 years.
• Presence of any contraindication to venous blood sampling for pharmacokinetic analyses.
• Positive SARS-CoV-2 test or hepatitis panel (including hepatitis B surface antigen [HBsAg] or hepatitis C virus antibody [anti-HCV]), or a positive HIV antibody screen
• Legal incapacity or limited legal capacity
• Participation in a clinical trial within 30 days prior to product administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NTRX-07 Low Dose Normal Volunteers; NTRX-07 administered orally once per day for 7 days	Drug: NTRX-07; Investigational orally administered CB2 agonist; Other Names: MDA7
Experimental: NTRX-07 Mid Dose Normal Volunteers; NTRX-07 administered orally once per day for 7 days	Drug: NTRX-07; Investigational orally administered CB2 agonist; Other Names: MDA7
Experimental: NTRX-07 High Dose Normal Volunteers; NTRX-07 administered orally once per day for 7 days	Drug: NTRX-07; Investigational orally administered CB2 agonist; Other Names: MDA7
Experimental: NTRX-07 High Dose Alzheimer's Participants; NTRX-07 administered orally once per day for 7 days	Drug: NTRX-07; Investigational orally administered CB2 agonist; Other Names: MDA7
Placebo Comparator: Placebo Control; Placebo administered orally once per day for 7 days	Drug: Placebo; Matched placebo administered orally
Experimental: Mid Dose Fed; NTRX-07 administered orally once with high fat meal	Drug: NTRX-07; Investigational orally administered CB2 agonist; Other Names: MDA7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Related Adverse Events	AEs observed and recorded according to MEDRA	From admission to discharge, up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Concentration of NTRX-07 NTRX-07	Pharmacokinetic profile of NTRX-07	Day 1 and Day 7
Maximum Concentration of NTRX-07 NTRX-07	Pharmacokinetic profile of NTRX-07	Day 1 and Day 7
Area Under the Plasma Concentration Versus Time Curve (AUC) NTRX-07	Pharmacokinetic profile of NTRX-07	Day 1 and Day 7

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of neuro-inflammatory biomarkers	TNF-α, IL-1β, IL-6, IL-2, YKL-40, sTREM2, Aβ40, Aβ42, phospho-tau, Neurogranin, synaptotagmin-1, NfL - pg/ml	Day 1 and Day 7
Plasma levels of high-sensitivity C-reactive protein (CRP)	high sensitivity CRP - ng/ml	Day 1 and Day 7
MOCA Montreal Cognitive Assessment	Cognitive changes on patient-reported outcomes - Scored 0-30, higher is better	Day 1 and Day 7
MMSE - Mini-Mental Status Exam	Cognitive changes on patient-reported outcomes - Scored 0-30, higher is better	Day 1 and Day 7
ADAS-COG - Alzheimer's Disease Assessment Scale - Cognitive Scale	Cognitive changes on patient-reported outcomes - Scored 0-70, higher is worse	Day 1 and Day 7

Collaborators and Investigators

• Sponsor: NeuroTherapia, Inc.
• Collaborators: CRU Early Phase Unit Kistarcsa

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Estimated): January 8, 2024

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: CB2
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: NTRX-C102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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