Progressive Supranuclear PalsyPhase 2NCT04993768
A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP)
A Phase 2 study testing TPN-101, 100 mg/day, TPN-101, 200 mg/day and TPN-101, 400 mg/day in people with Progressive Supranuclear Palsy, run by Transposon Therapeutics, Inc. at 14 sites in United States.
Trial summary
This is a Phase 2a study to assess the safety and tolerability of TPN-101 patients with PSP. Read more about this study
- Who is it for?
- Ages 41 to 86 years
- Conditions the study is for
- Progressive Supranuclear Palsy
- What is being tested?
- TPN-101, 100 mg/day, TPN-101, 200 mg/day and TPN-101, 400 mg/day
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 14 sitesUnited States
- Study dates
- 12 Dec 2021to 24 Mar 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 41 to 86 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Johns Hopkins University School of Medicine
Baltimore, Maryland, 21287
Parkinson's Disease and Movement Disorders Center of Boca Raton
Boca Raton, Florida, 33486
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Rocky Mountain Movement Disorders Center
Englewood, Colorado, 80113
Quest Research Institute
Farmington Hills, Michigan, 48334
UFHealth Fixel Institute for Neurological Diseases
Gainesville, Florida, 32608
UC San Diego Altman Clinical And Translational Research Institute
La Jolla, California, 92037
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106
Irving Center for Clinical and Translational Research
New York, New York, 10032
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
St. Joseph's Hospital and Medical Center, Barrow Neurological Institute
Phoenix, Arizona, 85013
Mayo Clinic
Rochester, Minnesota, 55905
UCSF Neurosciences Clinical Research Unit (NCRU)
San Francisco, California, 94158
About this study
This is a Phase 2a study to assess the safety and tolerability of TPN-101 patients with PSP.
Read the 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.
- Conditions
- Progressive Supranuclear Palsy
- Being tested
- TPN-101, 100 mg/day, TPN-101, 200 mg/day, TPN-101, 400 mg/day, Placebo
- Medical subject headings
- Supranuclear Palsy, Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPN-101, 100 mg/dayDrug
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).
TPN-101, 200 mg/dayDrug
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).
TPN-101, 400 mg/dayDrug
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).
PlaceboDrug
Placebo once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).
| Study group | Role | What they receive |
|---|---|---|
| TPN-101, Dose A | Experimental | Not described Receives: Drug: TPN-101, 100 mg/day |
| TPN-101, Dose B | Experimental | Not described Receives: Drug: TPN-101, 200 mg/day |
| TPN-101, Dose C | Experimental | Not described Receives: Drug: TPN-101, 400 mg/day |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 48 weeks
Secondary outcomes (3)
Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)
Measured: 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)
Measured: 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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2021
- Study start12 Dec 2021
- Primary completion24 Feb 2024
- Study completion24 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Transposon Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04993768
- Sponsor's protocol ID
- TPN-101-PSP-201
- Status last verified
- Apr 2026
- First submitted
- 19 Jul 2021
- Last updated
- 8 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Nicodemus J, Liu CS, Ransom L, Tan V, Romanow W, Jimenez N, Chun J. Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain. J Neurosci. 2025 Jun 18;45(25):e2298242025. doi: 10.1523/JNEUROSCI.2298-24.2025.
PubMed 40368603
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP)
- ClinicalTrials.gov ID
- NCT04993768
- Acronym / sponsor ID
- TPN-101-PSP-201
- Conditions
- Progressive Supranuclear Palsy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Transposon Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Dec 2021 (actual)
- Primary completion
- 24 Feb 2024 (actual)
- Study completion
- 24 Mar 2024 (actual)
- First posted
- 6 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TPN-101, Dose A | Experimental | Drug: TPN-101, 100 mg/day |
| TPN-101, Dose B | Experimental | Drug: TPN-101, 200 mg/day |
| TPN-101, Dose C | Experimental | Drug: TPN-101, 400 mg/day |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 41 to 86 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TPN-101, 100 mg/day100 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). | Drug | TPN-101, Dose A |
| TPN-101, 200 mg/day200 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). | Drug | TPN-101, Dose B |
| TPN-101, 400 mg/day400 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). | Drug | TPN-101, Dose C |
| PlaceboPlacebo once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment). | Drug | Placebo |
Primary outcome
Assess the safety and tolerability of TPN-101 in patients with progressive supranuclear palsy (PSP)
Time frame: 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
3 secondary outcomes
Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)
Time frame: 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)
Time frame: 48 weeks
Assess the clinical effect of TPN-101 as measured by changes in score on the Progressive Supranuclear Palsy Rating Scale (PSPRS)
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2026.
- Derived from this study: PubMed 40368603Nicodemus J, Liu CS, Ransom L, Tan V, Romanow W, Jimenez N, Chun J. Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain. J Neurosci. 2025 Jun 18;45(25):e2298242025. doi: 10.1523/JNEUROSCI.2298-24.2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TPN-101, 100 mg/day, TPN-101, 200 mg/day and TPN-101, 400 mg/day in people with Progressive Supranuclear Palsy, run by Transposon Therapeutics, Inc. at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the safety and tolerability of TPN-101 in patients with progressive supranuclear palsy (PSP) (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04993768, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2026.