A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP)

Study Overview
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Brief Summary
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This is a Phase 2a study to assess the safety and tolerability of TPN-101 patients with PSP.

Detailed Description
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This is a Phase 2a multi-center, randomized, double-blind, placebo-controlled parallel-group, 4-arm study with an open-label treatment phase in patients with PSP. This study includes a 6-week Screening Period, a 24-week Double-blind Treatment Period, a 24-week Open label Treatment Period, and a Follow-up Visit 4 weeks post treatment.

Official Title
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A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP)

Conditions
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Progressive Supranuclear Palsy

Intervention / Treatment
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* Drug: TPN-101, 100 mg/day
* Drug: TPN-101, 200 mg/day
* Drug: TPN-101, 400 mg/day
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of probable progressive supranuclear palsy (PSP) Presence of PSP symptoms for less than 5 years Has a reliable caregiver/informant to accompany the patient to all study visits. Score ≥ 18 on the Mini Mental State Exam (MMSE) at Screening Patient must reside outside a skilled nursing facility or dementia care facility at the time of Screening, and admission to such a facility must not be planned. Residence in an assisted living facility is allowed Exclusion Criteria: Patients must not meet any of the following criteria: Presence of other significant neurological or psychiatric disorders History of clinically significant brain abnormality Presence of cerebellar ataxia, choreoathetosis, early symptomatic autonomic dysfunction, or moderate to severe resting tremor, responsive to levodopa Known history of serum or plasma progranulin level less than one standard deviation below the normal patient mean Known presence of disease-associated mutation in TARDBP, GRN, CHMPB2, or VCP genes; or any other frontotemporal lobar degeneration causative genes not associated with underlying tau pathology History of clinically significant hematological, endocrine, cardiovascular, renal, hepatic, or gastrointestinal disease

Ages Eligible for Study
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Minimum Age: 41 Years
Maximum Age: 86 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TPN-101, Dose A<br> | Drug: TPN-101, 100 mg/day<br>* 100 mg/day of study investigational drug TPN-101 once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).<br>|
| Experimental: TPN-101, Dose B<br> | Drug: TPN-101, 200 mg/day<br>* 200 mg/day of study investigational drug TPN-101 once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).<br>|
| Experimental: TPN-101, Dose C<br> | Drug: TPN-101, 400 mg/day<br>* 400 mg/day of study investigational drug TPN-101 once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of TPN-101 in patients with progressive supranuclear palsy (PSP) | Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) associated with TPN-101 v. placebo administered for up to 48 weeks in patients with PSP | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF) |  | 48 weeks | 
| Assess the pharmacodynamic effect of TPN-101 on neurodegeneration as measured by changes in the levels of CSF and blood neurofilament light (NfL) |  | 48 weeks | 
| Assess the clinical effect of TPN-101 as measured by changes in score on the Progressive Supranuclear Palsy Rating Scale (PSPRS) | The PSPRS is comprised of 28 items in six categories: daily activities (by history), behavior, bulbar, ocular motor, limb motor and gait/midline. Scores range from 0 to 100, each item is graded 0-2 (six items) or 0-4 (22 items), with lower scores indicating better clinical and functional status. | 48 weeks |