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

Phase 2

Active, not recruiting

• Conditions: Progressive Supranuclear Palsy
• Interventions: Drug: TPN-101, 200 mg/day; Drug: TPN-101, 100 mg/day; Drug: TPN-101, 400 mg/day; Drug: Placebo

• Registration Number: NCT04993768
• Lead Sponsor: Transposon Therapeutics, Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-07-19
• Study First Submitted QC: 2021-07-29
• Study First Posted: 2021-08-06
• Study Start: 2021-10-15
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-12
• Last Update Posted: 2023-07-13
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TPN-101, Dose B	TPN-101, 200 mg/day	-
TPN-101, Dose A	TPN-101, 100 mg/day	-
TPN-101, Dose C	TPN-101, 400 mg/day	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Assess the safety and tolerability of TPN-101 in patients with progressive supranuclear palsy (PSP)	48 weeks	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

Secondary Outcome Measures

Name	Time	Method
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)	48 weeks	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.

Trial Locations

Locations (14)

Irving Center for Clinical and Translational Research; 🇺🇸 New York, New York, United States

Rocky Mountain Movement Disorders Center; 🇺🇸 Englewood, Colorado, United States

Parkinson's Disease and Movement Disorders Center of Boca Raton; 🇺🇸 Boca Raton, Florida, United States

St. Joseph's Hospital and Medical Center, Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

UCSF Neurosciences Clinical Research Unit (NCRU); 🇺🇸 San Francisco, California, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Cleveland Clinic Lou Ruvo Center for Brain Health; 🇺🇸 Las Vegas, Nevada, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Johns Hopkins University School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Quest Research Institute; 🇺🇸 Farmington Hills, Michigan, United States

UC San Diego Altman Clinical And Translational Research Institute; 🇺🇸 La Jolla, California, United States

UFHealth Fixel Institute for Neurological Diseases; 🇺🇸 Gainesville, Florida, United States