Feasibility Study in Subjects With Mild to Moderate Alzheimer's Disease

NCT02560753 | Completed Phase 1 Results

• 1 other identifier: T3D959-201
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

The study is a randomized, parallel, 4-dose design in subjects with mild-to-moderate Alzheimer's Disease. Subjects will be randomized to one of 4 doses of T3D-959. Subjects will be evaluated for changes from baseline in cerebral metabolic rate of glucose (FDG-PET imaging), functional connectivity of the hippocampus (BOLD-fMRI), and cognitive function (ADAS-Cog11 and DSST) as well as assessed for safety and tolerability to T3D-959. An expanded access extension is planed to provide access to study medication to subjects who have completed the main study and requested continued use.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• Change From Baseline (End of Treatment - Baseline) for FDG-PET Imaging With Whole Brain and White Matter as Reference Region

  Changes in relative brain glucose metabolism (delta R CMRgl) were measured by FDG-PET. At each time point, a ratio of the PET reading in a pre-defined region of interest (sROI), known to be affected by AD, and in a reference region (RR) that is spared in AD, is determined. This ratio is defined as "sROI index" (spared region). A second RR, brain white matter (WM), was also used in this calculation: sROI index" (WM) value. delta sROI is defined as change in the sROI index values, over the treatment period. In this study we are looking for changes in delta sROI with increasing doses of T3D-959. Dose dependent changes in delta sROI (AD spared) are compared to those observed with the WM as the RR: delta sROI (WM). Dose related changes in delta sROI suggests T3D-959 is entering the brain and effecting glucose metabolism in a dose dependent fashion.

  after 14 days of treatment

• The Effect of Treatment With T3D-959 on Changes in Resting State Blood Oxygen Level Dependent (BOLD) Signal in Functional Magnetic Resonance Imaging (fMRI) of the Brain Areas Associated With Cognitive Tasks.

  Changes in BOLD fMRI parameters such as GoF (see Study Description) over the course of two weeks of treatment, were obtained in this study. BOLD fMRI has been used in cross sectional and longitudinal studies of Alzheimer's subjects, for instance in the Alzheimer's Disease Neuroimaging Initiative studies. However, no studies monitoring Default Mode Networks measured parameters such as GoF, in the context of an effective AD therapeutic, as a result it is difficult to interpret the observed small changes listed in BOLD fMRI parameters obtained in this trial. Instead the changes in the listed BOLD fMRI parameters (EOT - BL) are reported without interpretation. These values represent changes in fMRI connectivity patterns over time and are unitless.

  after 14 days of treatment

Secondary Outcomes (2)

• Change From Baseline in the Score of the Digit Symbol Substitution Test

  after 14 days of treatment

• Change From Baseline in the Total Score of the 11-item Alzheimer's Disease Assessment Scale - Cognitive Subscale

  after 14 days of treatment

Other Outcomes (1)

• Safety and Tolerability of Treatment With T3D-959 Over a 2-week Period in Subjects With Mild-to-moderate AD. New

  after 14 days of treatment

Study Arms (4)

T3D-959 3mg

EXPERIMENTAL

Nine subjects will take 3mg by mouth once daily for two weeks, with or without food.

Drug: T3D-959

T3D-959 10mg

EXPERIMENTAL

Nine subjects will take 10mg by mouth once daily for two weeks, with or without food.

Drug: T3D-959

T3D-959 30mg

EXPERIMENTAL

Nine subjects will take 30mg by mouth once daily for two weeks, with or without food.

Drug: T3D-959

T3D-959 90mg

EXPERIMENTAL

Nine subjects will take 90mg by mouth once daily for two weeks, with or without food.

Drug: T3D-959

Interventions

T3D-959 DRUG

The 3mg dosage is supplied as 1mg capsules (three capsules, taken once daily by mouth) The 10mg dosage is supplied as 5mg capsules (two capsules, taken once daily by mouth) The 30mg dosage is supplied as either 5mg or 15mg capsules (six 5mg capsules or two 15mg capsules taken once daily by mouth) The 90mg dosage is supplied as 15mg capsules (six capsules, taken once daily by mouth)

T3D-959 10mg; T3D-959 30mg; T3D-959 3mg; T3D-959 90mg

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets criteria for mild-to-moderate AD with Mini-Mental State Examination (MMSE) score of 14 through 26
• Clinical Dementia Rating = 0.5 to 2.0
• Modified Hachinski less than or equal to 4
• A clinical diagnosis of AD per NINCDS-ADRDA criteria
• Washout of psychoactive medication (other than anti-depressants): at least 4 weeks prior to baseline
• Stability of all permitted medications for 4-12 weeks prior to baseline
• Visual and auditory acuity adequate for neuropsychological testing
• Home monitoring available for supervision of medications

You may not qualify if:

• Unstable diabetes or insulin use
• Unable to participate in FDG-PET scanning
• Inability to undergo a clinical MRI of the brain
• Diagnosis of significant neurological/psychiatric disease other than AD
• History of moderate or severe congestive heart failure, NYHA class III or IV, within 12 months prior to baseline.
• Previous cardiovascular event within the past 6 months prior to baseline
• Subject is pregnant, or lactating.
• ALT and/or AST levels that are twice the upper limit of normal; bilirubin levels that exceed 2 mg/dL; serum creatinine \>1.5 mg/dL in men or \> 1.4 mg/dL in women.
• Current or history of severe or unstable disorder (medical or psychiatric) requiring treatment that may make the subject unlikely to complete the study.
• Current use of fluvoxamine.
• Current unstable use of warfarin.
• Current use (within 30 days of baseline, visit 2) of certain highly protein-bound medications
• Malignancy within the last 5 years (other than non-melanoma skin cancer, stable, non-progressive prostate cancer not requiring treatment or in situ cervical cancer).
• Known history of HIV, hepatitis B, or hepatitis C.
• Blood pressure greater than 160/100 mmHg.

Sponsors & Collaborators

• T3D Therapeutics, Inc.: lead

Study Sites (3)

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

New Hope Clinical Research

Charlotte, North Carolina, 28204, United States

Location

Related Publications (2)

• Tong M, Dominguez C, Didsbury J, de la Monte SM. Targeting Alzheimer's Disease Neuro-Metabolic Dysfunction with a Small Molecule Nuclear Receptor Agonist (T3D-959) Reverses Disease Pathologies. J Alzheimers Dis Parkinsonism. 2016 Jun;6(3):238. doi: 10.4172/2161-0460.1000238. Epub 2016 Jun 3.

  PMID: 27525190 DERIVED

• Tong M, Deochand C, Didsbury J, de la Monte SM. T3D-959: A Multi-Faceted Disease Remedial Drug Candidate for the Treatment of Alzheimer's Disease. J Alzheimers Dis. 2016;51(1):123-38. doi: 10.3233/JAD-151013.

  PMID: 26836193 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: John Didsbury, PhD
• Organization: T3DTherapeutics

didsj919@t3dtherapeutics.com

9199490517

Study Officials

• John Didsbury, Ph.D.

  T3DTherapeutics, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2015
• First Posted: September 25, 2015
• Study Start: July 1, 2015
• Primary Completion: May 30, 2016
• Study Completion: June 30, 2016
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2018-07

Locations

US (3)