TPN-101 for Progressive Supranuclear Palsy

Recruiting at 16 trial locations

Overseen By Jay Soto

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Transposon Therapeutics, Inc.

Disqualifiers: Neurological, Psychiatric, Brain abnormality, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests TPN-101 to determine its safety and tolerability for individuals with progressive supranuclear palsy (PSP), a brain disorder affecting movement, balance, and eye movements. Participants will receive either a placebo (a substance with no active treatment) or one of three doses of TPN-101 to compare effects. The trial seeks individuals diagnosed with PSP who have experienced symptoms for less than five years. Participants should not currently reside in a skilled nursing facility, though living in an assisted living facility is acceptable. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the TPN-101 trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TPN-101 is safe for use. In earlier studies, patients handled TPN-101 well, and no major side effects were reported. The FDA granted it fast track status, indicating promise in safety and effectiveness.

TPN-101 also lowers certain markers in the body linked to brain cell damage and inflammation, suggesting it might help protect brain health. Overall, studies so far indicate that TPN-101 is safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TPN-101 for Progressive Supranuclear Palsy because it targets a novel mechanism compared to current treatments. Most existing options, like levodopa or amantadine, focus on managing symptoms but don't address the underlying disease progression. TPN-101, however, is believed to interact with tau protein pathways, which are directly involved in the disease's progression. This new approach has the potential not just to alleviate symptoms but to slow down or alter the course of the disease itself, offering hope for more effective long-term management.

What evidence suggests that this trial's treatments could be effective for Progressive Supranuclear Palsy?

Research has shown that TPN-101 might help treat progressive supranuclear palsy (PSP). In one study, participants who took TPN-101 for 48 weeks did not experience an increase in NfL levels, which are linked to nerve cell damage. TPN-101 also appears to lower NfL and IL-6 levels, markers related to inflammation and nerve damage. These findings suggest that TPN-101 could slow the progression of PSP by targeting these harmful markers. Although more research is needed, these results offer hope for those affected by PSP. Participants in this trial will receive one of various doses of TPN-101 or a placebo to further evaluate its effectiveness. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for patients with Progressive Supranuclear Palsy (PSP) who've had symptoms for less than 5 years and have a probable PSP diagnosis. Participants need to score at least 18 on the Mini Mental State Exam, live outside of nursing facilities, and have a reliable caregiver. It's not for those with certain genetic mutations or significant neurological, psychiatric, or other serious health issues.

Inclusion Criteria

You have been experiencing symptoms of PSP for less than 5 years.

Has a reliable caregiver/informant to accompany the patient to all study visits

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

Your progranulin level in your blood is significantly lower than normal.

You have specific genetic mutations known to cause frontotemporal lobar degeneration, except those related to tau pathology.

You have other important brain or mental health conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Double-blind Treatment

Participants receive either TPN-101 or placebo in a double-blind manner

24 weeks

Open-label Treatment

Participants receive TPN-101 in an open-label manner

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• TPN-101

Trial Overview The study tests the safety and tolerability of TPN-101 at different doses (100 mg/day, 200 mg/day, and 400 mg/day) compared to a placebo in people with PSP. The goal is to find out how well patients handle the medication.

How Is the Trial Designed?

Group I: TPN-101, Dose C Experimental Treatment 1 Intervention

Group II: TPN-101, Dose B Experimental Treatment 1 Intervention

Group III: TPN-101, Dose A Experimental Treatment 1 Intervention

Group IV: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Transposon Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

100+

Published Research Related to This Trial

In a study involving 187 patients with progressive supranuclear palsy (PSP), the PSP-Rating Scale was identified as the most efficient measure for detecting significant changes in disease progression, requiring only 51 patients per group for a 50% change over one year.

The study found no detectable placebo effect on the PSP-Rating Scale or the Schwab and England Activities of Daily Living, suggesting that these scales can reliably assess treatment efficacy in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy. Stamelou, M., Schöpe, J., Wagenpfeil, S., et al.[2021]

A new quantitative MRI analysis method was developed to measure disease progression in progressive supranuclear palsy (PSP), using data from 99 patients in two clinical trials, which can help in designing future studies.

The study identified that changes in the volumes of the third ventricle, midbrain, and frontal lobe are effective indicators of disease progression, requiring fewer patients to detect treatment efficacy compared to traditional clinical scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal magnetic resonance imaging in progressive supranuclear palsy: A new combined score for clinical trials. Höglinger, GU., Schöpe, J., Stamelou, M., et al.[2018]

There is currently no effective treatment for progressive supranuclear palsy (PSP), as most studies have shown negative outcomes and there are no randomized controlled trials to establish therapeutic standards.

The review highlights the ongoing challenges in developing effective therapies for PSP and suggests that future strategies may be needed to address this unmet medical need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward future therapies in progressive supranuclear palsy. Burn, DJ., Warren, NM.[2005]

Citations

1. prnewswire.com prnewswire.com/news-releases/transposon-announces-final-results-from-a-phase-2-study-of-its-line-1-reverse-transcriptase-inhibitor-tpn-101-for-the-treatment-of-progressive-supranuclear-palsy-and-interim-results-from-a-phase-2-study-of-tpn-101-for-the-treatmen-302060254.html

Transposon Announces Final Results from a Phase 2 ... Participants treated with 400 mg TPN-101 for the entire 48-week treatment period showed no increase of NfL levels in the CSF from weeks 1 to 48.

2. neurologylive.com neurologylive.com/view/transposon-therapeutics-tpn-101-progressive-supranuclear-palsy-fast-tracked

Transposon Therapeutics' TPN-101 for Progressive ... TPN-101 has shown promising results in reducing neurofilament light chain (NfL) and interleukin 6 (IL-6) levels in patients with progressive ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04993768

NCT04993768 | A Phase 2a Study of TPN-101 in Patients ... Outcome Measure, Measure Description, Time Frame. Assess the safety and tolerability of TPN-101 in patients with progressive supranuclear palsy (PSP), Incidence ...

4. theaftd.org theaftd.org/posts/1ftd-in-the-news/b-transposon-therapeutics-psp-2/

Transposon Therapeutics Receives Fast Track Designation ... The trial results showed that the drug reduced levels of multiple biomarkers associated with neurodegeneration, with Transposon noting that ...

5. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/transposon

Study of TPN-101 in Patients with Progressive ... The main purpose of this study is to investigate the safety and tolerability (whether side effects can be handled by a patient) of TPN-101 compared to a placebo ...

6. transposonrx.com transposonrx.com/pdf/Transposon%20-%20Press%20Release%20-%20Final%20C9%20Results%20-%20July%2024,%202024.pdf

Transposon Announces Final Results from a Phase ... Final results from this study confirmed the excellent safety profile of TPN-101 and showed clinical signs of disease-modifying effects in ...