CompletedPhase 2

A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD

A Phase 2a Study of TPN-101 in Patients With Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD) Associated With Hexanucleotide Repeat Expansion in the C9orf72 Gene (C9ORF72 ALS/FTD)

Lead sponsor

Transposon Therapeutics, Inc.

Asset

TPN-101

Listed sites

Recruiting sites

Enrollment

actual

Study population

Frontotemporal dementia

Key I/E criterion

•Study partner/caregiver required

Primary endpoint

•Assess the safety and tolerability of TPN-101

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04993755

Org study IDTPN-101-C9-201

Timeline

Milestones

Study first posted2021-08-06actual

Study start2021-10-01actual

Primary completion2023-08-17actual

Study completion2023-09-01actual

Last update posted2026-04-03actual

Assets

Drug assets

TPN-101

Study populations

Who this study enrolls

Frontotemporal dementia

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Documentation of a clinical genetic test demonstrating a hexanucleotide repeat expansion (HRE) in the C9orf72 gene

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

For patients with ALS (with or without FTD):

•Diagnosis of ALS (probable, possible, laboratory-supported probable or definite) according to the World Federation of Neurology revised E1 Escorial criteria

•Onset of weakness within 3 years prior to Screening

•Slow vital capacity (SVC) ≥ 60% of predicted normal adjusted for sex, age, and height (from the sitting position)

•Able to perform reproducible pulmonary function tests.

•ALS Functional Rating Scale-Revised (ALSFRS-R) ≥ 30 and score of 3 or 4 on Item #3 (swallowing) at Screening

For patients with FTD:

•A gradual, progressive decline in behavior, language, or motor function consistent with mild cognitive impairment, mild behavioral impairment, mild cognitive/behavioral impairment, behavioral variant FTD, primary progressive aphasia, or amnestic syndrome

•CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD) global score of 0.5-2.0 at Screening

Exclusion criteria

•Presence of other significant neurological or psychiatric disorders

•History of clinically significant brain abnormality

•Clinically significant medical illness

•Tracheostomy or diaphragmatic pacing

•Autoimmune disease requiring treatment or management (quiescent rheumatoid arthritis, psoriasis, or controlled Type 1 diabetes are acceptable)

•History of human immunodeficiency virus (HIV) or hepatitis B infection, or any active infection during Screening, unless the patient will have been symptom-free for at least 30 days prior to randomization

Endpoints (4)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Executive function / language

Neurodegeneration biomarkers

Fluid / digital biomarkers

Safety / tolerability / PK

Executive function / language

1 endpoint

Secondary/protocol endpoint

Assess the clinical effect of TPN-101 as measured by changes in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)

Time frame:48 weeks

descriptive

Neurodegeneration biomarkers

1 endpoint

Secondary/protocol endpoint

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

Neurofilament light (NfL)

ratio, descriptive

Fluid / digital biomarkers

1 endpoint

Secondary/protocol endpoint

Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)

Time frame:48 weeks

concentration, descriptive

Safety / tolerability / PK

1 endpoint

Primary/protocol endpoint

Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)

Time frame:48 weeks

event count, event

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID40368603via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.