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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Progressive Supranuclear Palsy
• Intervention / Treatment: Drug: TPN-101, 400 mg/day; Drug: Placebo; Drug: TPN-101, 100 mg/day; Drug: TPN-101, 200 mg/day

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center, Barrow Neurological Institute
  • California
    • La Jolla, California, United States, 92037
      • UC San Diego Altman Clinical and Translational Research Institute
    • San Francisco, California, United States, 94158
      • UCSF Neurosciences Clinical Research Unit (NCRU)
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Gainesville, Florida, United States, 32608
      • UFHealth Fixel Institute for Neurological Diseases
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New York
    • New York, New York, United States, 10032
      • Irving Center for Clinical and Translational Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Clinical diagnosis of probable progressive supranuclear palsy (PSP)
2. Presence of PSP symptoms for less than 5 years
3. Has a reliable caregiver/informant to accompany the patient to all study visits.
4. Score ≥ 18 on the Mini Mental State Exam (MMSE) at Screening
5. 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:

1. Presence of other significant neurological or psychiatric disorders
2. History of clinically significant brain abnormality
3. Presence of cerebellar ataxia, choreoathetosis, early symptomatic autonomic dysfunction, or moderate to severe resting tremor, responsive to levodopa
4. Known history of serum or plasma progranulin level less than one standard deviation below the normal patient mean
5. 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
6. History of clinically significant hematological, endocrine, cardiovascular, renal, hepatic, or gastrointestinal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).
Experimental: TPN-101, Dose A	Drug: TPN-101, 100 mg/day; 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).
Experimental: TPN-101, Dose B	Drug: TPN-101, 200 mg/day; 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).
Experimental: TPN-101, Dose C	Drug: TPN-101, 400 mg/day; 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Transposon Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: July 19, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): July 13, 2023
• Last Update Submitted That Met QC Criteria: July 12, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Paralysis; Ophthalmoplegia; Supranuclear Palsy, Progressive
• Other Study ID Numbers: TPN-101-PSP-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No