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)

Study Purpose:

This is a Phase 2a study to assess the the safety and tolerability 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).

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis , Frontotemporal Dementia

Study Type:


Type of Intervention:


Intervention Name:

TPN-101, 400 mg/day, Placebo




Phase 2

Study Chair(s)/Principal Investigator(s):


Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

United States

Full Study Summary:

This is a Phase 2a multi-center, randomized, double-blind, placebo-controlled parallel-group, 2-arm study with a long-term, open-label treatment phase in patients with C9ORF72 ALS and/or FTD. 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 Sponsor:

Transposon Therapeutics, Inc.

Estimated Enrollment:


Estimated Study Start Date:

10 / 01 / 2021

Estimated Study Completion Date:

09 / 01 / 2023

Posting Last Modified Date:

03 / 06 / 2023

Date Study Added to neals.org:

08 / 06 / 2021

Minimum Age:

18 Years

Maximum Age:


Can participants use Riluzole?


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

University of California San Diego

La Jolla, California 92037
United States

University of California Irvine - ALS & Neuromuscular Center

Orange, California 92868
United States

UCSF Neurosciences Clinical Research Unit (NCRU)

San Francisco, California 94158
United States

John Hopkins University

Baltimore, Maryland 21287
United States

Johns Hopkins Outpatient Center

Baltimore, Maryland 21287
United States

Massachusetts General Hospital (MGH) - Amyotrophic Lateral Sclerosis (ALS) Multidisciplinary Clinic

Boston, Massachusetts 02114
United States

Mayo Family Clinic Northwest

Rochester, Minnesota 55905
United States

Hospital for Special Surgery

New York, New York 10021
United States

Columbia University Medical Center - The Neurological Institute of New York

New York, New York 10032
United States

The University of North Carolina at Chapel Hill, Department of Neurology

Chapel Hill, North Carolina 27599
United States

VIB-KU Leuven Center for Brain & Disease Research

Leuven, Flemish Brabankt 3000

CHU Lille - CMRR Hôpital Roger Salengro

Lille 59037

CHU Dupuytren, Limoges

Limoges 87042

Groupe Hospitalier Pitie-Salpetriere - La Federation de Maladies du Systeme Nerveux

Paris 75013

Universitaetsklinikum Ulm - Klinik fuer Neurologie

Ulm, Baden-Wuerttemberg 89081

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, A Coruña 15706ES

Hospital de la Santa Creu i Sant Pau

Barcelona 08025

Hospital Universitario Vall d'Hebron

Barcelona 08035ES

Hospital Universitari I Politècnic La Fe

Valencia 46026