A Phase 1 interventional study of TPI-287 2 mg/m2 and TPI-287 6.3 mg/m2 in Alzheimer's Disease, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 50 Years to 82 Years. Per ClinicalTrials.gov, last updated 2020-04-14.
Sponsored by University of California, San Francisco · Phase 1, Interventional, and Other
The purpose of the study is to determine the highest dose of TPI-287 that is safe and tolerable when administered as an intravenous infusion to participants with mild to moderate Alzheimer's disease (AD), to measure pharmacokinetic properties of the drug as well as to gauge preliminary efficacy of TPI-287 on disease progression.
The maximum tolerated dose of TPI-287 will be determined through a planned dose escalation over 3 sequential cohorts, each comprising of 11 participants randomized to either TPI-287 or placebo. TPI-287 or placebo will be administered as an intravenous infusion once every 3 weeks for 9 weeks, for a total of 4 infusions. Participants who successfully complete this phase will have the option of entering into the open label extension phase during which TPI-287 will be administered once every 3 weeks for an additional 6 weeks, for a total of 3 extra infusions.
Pre-medication of diphenhyramine 25 mg (Benadryl) will be given IV within 30 to 60 minutes prior to each study infusion in the study.
Safety and tolerability will be assessed through reporting of adverse events, physical and neurological testing, ECGs, as well as blood and urine analyses. Baseline and end-point measures of cognition and function, MRI brain scans, and cerebrospinal fluid (CSF) biomarker analyses will be used to determine preliminary efficacy of TPI-287 in mild-moderate AD. Pharmacokinetic and pharmacodynamic properties of TPI-287 will be calculated from blood plasma collected after the first infusion, and from CSF collected on the last visit of the placebo-controlled phase.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 29 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
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Inclusion Criteria (all must be met):
Exclusion Criteria (any one of the following will exclude a subject from being enrolled into the study):
2 mg/m2 of TPI-287 administered as a 1-hour intravenous infusion once every 3 weeks for 9 weeks (for a total of 4 infusions)
Drug: TPI-287 2 mg/m2 · Drug: Placebo
6.3 mg/m2 of TPI-287 administered as a 1-hour intravenous infusion once every 3 weeks for 9 weeks (for a total of 4 infusions)
Drug: TPI-287 6.3 mg/m2 · Drug: Placebo
20 mg/m2 of TPI-287 administered as a 1-hour intravenous infusion once every 3 weeks for 9 weeks (for a total of 4 infusions)
Drug: TPI-287 20 mg/m2 · Drug: Placebo
Drug: Placebo
2 mg/m2 of TPI-287 diluted with 500mL 0.9% sodium chloride. TPI-287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class.
6.3 mg/m2 of TPI-287 diluted with 500mL 0.9% sodium chloride. TPI-287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class.
20 mg/m2 of TPI-287 diluted with 500mL 0.9% sodium chloride. TPI-287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class.
500mL 0.9% sodium chloride.
Maximum tolerated dose of TPI-287
Planned dose range of intravenous infusions of TPI-287 administered once every 3 weeks for 9 weeks. The dose will be escalated in 3 sequential cohorts and participants will be monitored for adverse events to determine safety and tolerability.
Time frame: up to 13 weeks post initial dosing
TPI-287 levels in blood plasma and cerebrospinal fluid
Blood plasma will be collected at specified time-points before and following the first infusion of study drug (TPI-287 or placebo) to measure TPI-287 levels. Steady-state levels of TPI-287 will be estimated from cerebrospinal fluid collected at end-point visit of placebo-controlled phase. These levels will be used to estimate the pharmacokinetic properties of TPI-287.
Time frame: Screening and Week 10
CSF biomarkers of Alzheimer's disease
A lumbar puncture will be performed at the screening and final visits to obtain cerebrospinal fluid (CSF). CSF will be analyzed for changes to concentration of biomarkers of Alzheimer's disease - beta amyloid (1-42), total tau, phosphorylated tau, tau isoforms and fragments, and tau phosphopeptides.
Time frame: Screening and Week 10
Brain MRI scan
Brain MRI scans will be performed to explore effects of changes in brain network functional and structural connectivity as well as perfusion after administration of study drug.
Time frame: Screening and Week 11
Cognition
The Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) and Mini Mental State Examination (MMSE) will be conducted to determine effect and preliminary efficacy of the drug on cognition.
Time frame: Screening and Week 11
Degree of disability
The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) will be conducted to determine effect and preliminary efficacy of the drug on degree of disability.
Time frame: Screening and Week 11
Behavior
The Geriatric Depression Scale (GDS) will be conducted to determine effect and preliminary efficacy of the drug on behavior.
Time frame: Screening and Week 11
Number of participants with adverse events as a measure of safety and tolerability of extended administration of TPI-287
Participants who successfully complete the placebo controlled phase will be offered the option to enter an open label extension phase comprising of 3 additional infusions of TPI-287, administered once every 3 weeks for 6 weeks. Participants will be monitored for adverse events to determine drug safety and tolerability.
Time frame: up to 20 weeks post initial dosing
This study is completed, as verified in Apr 2020. You cannot join it, but the record below documents what was studied.
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University of California, San Francisco