Ignite Creation Date:
2024-05-06 @ 7:36 AM
Last Modification Date:
2024-10-26 @ 11:50 AM
Study NCT ID:
NCT02560753
Status:
COMPLETED
Last Update Posted:
2018-07-30
First Post:
2015-07-28
Brief Title:
Feasibility Study in Subjects With Mild to Moderate Alzheimers Disease
Sponsor:
T3D Therapeutics Inc
Organization:
T3D Therapeutics Inc
Study Overview
Official Title:
Phase 2a Feasibility Study of T3D-959 in Subjects With Mild to Moderate Alzheimers Disease
Status:
COMPLETED
Status Verified Date:
2018-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The study is a randomized parallel 4-dose design in subjects with mild-to-moderate Alzheimers 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
An expanded access extension is planed to provide access to study medication to subjects who have completed the main study and requested continued use
Detailed Description:
T3D-959 is an orally-delivered once-a-day administered small molecule dual nuclear receptor agonist that has been shown in animal and Phase 1 studies in normal human subjects to be safe and well tolerated The purpose of this clinical study in AD patients is to demonstrate mechanistic proof of concept that T3D-959 can produce desired changes in cerebral glucose metabolism and functional connectivity that may indicate potential for cognitive improvement The therapeutic approach to be tested is based on two suppositions A ameliorating multiple pathologies in the disease with a single therapy may provide a superior clinical benefit than therapeutic approaches which target a single pathology and B correcting insulin resistance in the brain highly correlated with AD and potential key driver of AD pathophysiology and peripherally may be disease remedial
The brain requires integral insulin signaling for metabolic homeostasis and neuronal plasticity Insulin resistance disrupts energy balance and signaling networks needed for a broad range of functions Impaired insulin signaling in neurons enhances apoptosis promotes oxidative cell death induced by Abeta1-42 increases secretion of Abeta1-42 blocks removal of extracellular Abeta oligomers and increases plaque loads A growing body of evidence suggests that brain insulin resistance promotes or possibly is the trigger of key pathologies in AD and is supported by observed changes in levels of insulin signaling molecules in AD forebrains and associated changes in memory Pre-clinical studies in animals have demonstrated the insulin sensitizing activity of T3D-959 and ability to improve multiple pathologies of AD in a rat model of disease
This non-placebo controlled trial will be conducted in one to three clinical centers Thirty six 36 patients with mild-to-moderate Alzheimers disease will be randomly assigned to once daily orally administered treatment with 3mg 10mg 30mg or 90mg doses of T3D-959 Participants will be treated for two weeks and will undergo at baseline and at two weeks FDG-PET scans to measure brain glucose metabolism BOLD fMRI scans to measure functional connectivity of the hippocampus venous blood draws for biomarker analysis and ApoE genotyping and ADAS-Cog11 and DSST cognitive testing For monitoring potential toxicities of the drug subjects will undergo physical examination neurological examination adverse event review blood chemistries and pharmacokinetic PK analyses for T3D-959 plasma levels
BOLD fMRI definition of terms
GoF Goodness of Fit The degree to which the spatial extent and magnitude of one subjects default mode network DMN regions matches the one of an elderly control group
Hippo-PreC Link Hippocampus - Precuneus Link The resting-state BOLD signal correlation strength between hippocampus and precuneus regions of interest
GlobEff_DMN Global Efficiency from DMN Regions The global efficiency among 11 pre-defined default mode network regions
GlobEff_AAL Global Efficiency from AAL Regions The global efficiency among 90 pre-defined cerebral regions based on automated anatomical labeling
ALFF_lPCC_PreC Amplitude of Low Frequency Fluctuations ALFF from left posterior cingulate cortex PCC and precuneus PreC
ALFF_rPCC_PreC ALFF from right PCC and precuneus fALFF_lPCC_PreC Ratio ALFF from left PCC and precuneus fALFF_rPCC_PreC Ratio ALFF from right PCC and precuneus ReHo_lPCC_PreC Regional Homogeneity in left PCC and PreC ReHo_rPCC_PreC Regional Homogeneity in right PCC and PreC ALFF_lIPL ALFF from left inferior parietal lobule IPL ALFF_rIPL ALFF from right IPL fALFF_lIPL Ratio ALFF from left IPL fALFF_rIPL Ratio ALFF from right IPL ReHo_lIPL Regional Homogeneity in left IPL ReHo_rIPL Regional Homogeneity in right IPL
Expanded Access Extension This is an open label 10 visit extension for up to 5 subjects who have completed the T3D959-201 protocol and whose caregivers and physician requested their continued treatment in an expanded access protocol All subjects enrolled in this study will be treated with a 15mg qd dose of T3D959 for six months regardless of their assigned dose level from the main study A continued riskbenefit assessment by the investigator will be conducted at each visit to determine the need for treatment continuation Subjects will be assessed for safety and tolerability to T3D-959 and evaluated for changes from baseline cognitive function via ADAS-Cog11 and DSST testing and global change via CIBIC-plus testing
The brain requires integral insulin signaling for metabolic homeostasis and neuronal plasticity Insulin resistance disrupts energy balance and signaling networks needed for a broad range of functions Impaired insulin signaling in neurons enhances apoptosis promotes oxidative cell death induced by Abeta1-42 increases secretion of Abeta1-42 blocks removal of extracellular Abeta oligomers and increases plaque loads A growing body of evidence suggests that brain insulin resistance promotes or possibly is the trigger of key pathologies in AD and is supported by observed changes in levels of insulin signaling molecules in AD forebrains and associated changes in memory Pre-clinical studies in animals have demonstrated the insulin sensitizing activity of T3D-959 and ability to improve multiple pathologies of AD in a rat model of disease
This non-placebo controlled trial will be conducted in one to three clinical centers Thirty six 36 patients with mild-to-moderate Alzheimers disease will be randomly assigned to once daily orally administered treatment with 3mg 10mg 30mg or 90mg doses of T3D-959 Participants will be treated for two weeks and will undergo at baseline and at two weeks FDG-PET scans to measure brain glucose metabolism BOLD fMRI scans to measure functional connectivity of the hippocampus venous blood draws for biomarker analysis and ApoE genotyping and ADAS-Cog11 and DSST cognitive testing For monitoring potential toxicities of the drug subjects will undergo physical examination neurological examination adverse event review blood chemistries and pharmacokinetic PK analyses for T3D-959 plasma levels
BOLD fMRI definition of terms
GoF Goodness of Fit The degree to which the spatial extent and magnitude of one subjects default mode network DMN regions matches the one of an elderly control group
Hippo-PreC Link Hippocampus - Precuneus Link The resting-state BOLD signal correlation strength between hippocampus and precuneus regions of interest
GlobEff_DMN Global Efficiency from DMN Regions The global efficiency among 11 pre-defined default mode network regions
GlobEff_AAL Global Efficiency from AAL Regions The global efficiency among 90 pre-defined cerebral regions based on automated anatomical labeling
ALFF_lPCC_PreC Amplitude of Low Frequency Fluctuations ALFF from left posterior cingulate cortex PCC and precuneus PreC
ALFF_rPCC_PreC ALFF from right PCC and precuneus fALFF_lPCC_PreC Ratio ALFF from left PCC and precuneus fALFF_rPCC_PreC Ratio ALFF from right PCC and precuneus ReHo_lPCC_PreC Regional Homogeneity in left PCC and PreC ReHo_rPCC_PreC Regional Homogeneity in right PCC and PreC ALFF_lIPL ALFF from left inferior parietal lobule IPL ALFF_rIPL ALFF from right IPL fALFF_lIPL Ratio ALFF from left IPL fALFF_rIPL Ratio ALFF from right IPL ReHo_lIPL Regional Homogeneity in left IPL ReHo_rIPL Regional Homogeneity in right IPL
Expanded Access Extension This is an open label 10 visit extension for up to 5 subjects who have completed the T3D959-201 protocol and whose caregivers and physician requested their continued treatment in an expanded access protocol All subjects enrolled in this study will be treated with a 15mg qd dose of T3D959 for six months regardless of their assigned dose level from the main study A continued riskbenefit assessment by the investigator will be conducted at each visit to determine the need for treatment continuation Subjects will be assessed for safety and tolerability to T3D-959 and evaluated for changes from baseline cognitive function via ADAS-Cog11 and DSST testing and global change via CIBIC-plus testing
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None