Alzheimer's Disease
Conditions
Keywords
T3D-959, Mild-to-Moderate Alzheimer's Disease Severity, New Drug Treatment Being Tested, Once-a-day oral drug administration, Phase 2b/3 Study T3D959-301, Brain Metabolism
Brief summary
This study is a Phase 2b/3 clinical trial of a new candidate drug (T3D-959) to treat patients with mild-to-moderate Alzheimer's. The aims of the trial are to affirm potential therapeutic efficacy and safety observed in earlier clinical trials and assess the potential to modify the course of disease. The drug will be compared to placebo and administered orally to patients once a day for 78 weeks.
Detailed description
This study is a randomized, double-blind, placebo-controlled study of T3D-959 30mg in subjects with clinical mild-to-moderate Alzheimer's Disease and a biological diagnosis of AD pathology, as defined by a validated plasma biomarker (presently %p-tau217 plasma biomarker). This study is designed as a seamless group sequential design where estimates of treatment effect on cognitive and functional scales will be evaluated in an interim analysis by independent statisticians. The sample size will be re-estimated to ensure the study is sufficiently powered to demonstrate efficacy of T3D-959 in cognition and function. Subjects will be assigned to one of two treatment arms (1:1 ratio) in a randomized, double-blind fashion, stratified by sex and ApoE4 genotype. Study medication will be taken once daily for 78 weeks. Safety/tolerability, efficacy and exploratory assessments will be evaluated for changes from baseline to end of treatment (78 weeks). Subjects will be followed for four weeks after the end of treatment.
Interventions
DRUGT3D-959
Experimental: T3D-959 30 mg dose: T3D-959 is a small molecule dual nuclear receptor agonist that regulates transcription of genes, in particular those involved in glucose energy and lipid metabolism. T3D-959 is 15-times more potent for PPAR delta than for the secondary target of the drug, PPAR gamma. The 15 mg strength capsules contain 15mg T3D-959, pregelatinized starch NF, magnesium stearate NF, and size 0, hard gelatin, white/white, opaque, unmarked capsules. Subjects will ingest two size 0, 15mg capsules once per day in the morning.
OTHERPlacebo Comparator
Placebo used to compare to T3D-959 drug
Sponsors
T3D Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subject aged 50-90 years old inclusive at the time of Informed Consent 2. Subject (or legal representative) and caregiver must sign an Informed Consent to participate in the study. 3. Subject has a caregiver, an identified adult who, in the opinion of the investigator, has sufficient contact to knowledgeably report on the subject's cognition, function, behavior, safety, compliance and adherence. Same caregiver should, whenever possible, assist the subject throughout the duration of the trial 4. Subject has a biological diagnosis of AD pathology, as assessed by a validated plasma biomarker (presently %p-tau217 plasma biomarker), according to the NIA-AA (National Institute of Aging - Alzheimer's Association) criteria at screening 5. Subject has a clinical diagnosis of mild to moderate AD (Stage 4 or 5) according to the NIA-AA (National Institute of Aging - Alzheimer's Association) criteria at screening 6. Meets criteria for mild-to-moderate cognitive impairment with Mini-Mental State Examination (MMSE) score of 14 through 26 at the screening visit. 7. Modified Hachinski \< 4 at screening 8. Clinical Dementia Rating is 0.5 to 2.0 at screening 9. Visual and auditory acuity adequate for neuropsychological testing 10. Medical stability for this study as confirmed by review of records, comprehensive physical exam, neurological exam, and laboratory tests 11. Washout and stability of all concurrent medication according to the
Exclusion criteria
listed below 12. Able to swallow oral medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to end of treatment in ADAS-Cog13 and ADCS-iADL | 78 weeks | Primary Efficacy Endpoint • Co-primary endpoints of Alzheimer's Disease Assessment Scale cognitive subscale, 13-items (ADAS-Cog13) with a score range of 0-85 (higher scores indicating greater dysfunction) and Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living (ADCS-iADL) with a score range of 0-56 (lower scores indicating worse performance), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology. ADAS-cog 13 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to End of Treatment in plasma AB42/40 ratio, in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology | 78 weeks | — |
| Change from Baseline to End of Treatment in disease stage progression on the Clinical Dementia Rating Scale-Global (CDR-Global), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology | 78 weeks | CDR global score has a range of 0-3 with a higher score indicating greater dementia severity |
| Change from baseline to end of treatment in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology | 78 weeks | CDR-SB has a score range of 0-18 with a higher number indicating greater dementia severity |
| Change from Baseline to End of Treatment on the integrated Alzheimer's Disease Rating Scale (iADRS), in subjects with a clinical diagnosis of mild-to-moderate AD and biological diagnosis of AD pathology | 78 weeks | The iADRS is a composite scale that is calculated as a linear combination of total scores of the two individual components, the ADAS-Cog13 (score range 0-85) and the instrumental items of the ADCS-ADL (ADCS-iADL; score range 0-56)1 • The iADRS score ranges from 0-141 with lower scores indicating worse performance. |
Other
| Measure | Time frame |
|---|---|
| Additional Endpoints (Exploratory) • Change from Baseline to End of Treatment in plasma proteomic biomarker levels (i.e. Neurogranin, GFAP, MTBR-243) | 78 weeks |
Countries
United States
Contacts
Primary ContactBlake E Swearingen, MS
Backup ContactJohn Didsbury, Ph.D., Chief Executive Officer
Outcome results
None listed