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:



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

Jay Soto / email hidden; JavaScript is required / 310-261-5312

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:

11 / 08 / 2022

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 | Recruiting

Dominic Ferrey, MD

La Jolla, California 92037
United States

University of California Irvine - ALS & Neuromuscular Center | Recruiting

Namita A Goyal, MD

Orange, California 92868
United States

University of California at San Francisco/UCSF | Recruiting

Adam Boxer, MD, PhD

San Francisco, California 55455
United States

John Hopkins University | Recruiting

Chiadi Onyike, M.B.B.S., MD

Baltimore, Maryland 21287
United States

Johns Hopkins Outpatient Center | Recruiting

Jeffrey D Rothstein, MD, PhD

Baltimore, Maryland 21287
United States

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

Doreen Ho, MD

Boston, Massachusetts 02114
United States

Mayo Family Clinic Northwest | Recruiting

Bradley Boeve, MD

Rochester, Minnesota 55905
United States

Hospital for Special Surgery | Recruiting

Dale J Lange, MD

New York, New York 10021
United States

Columbia University Medical Center - The Neurological Institute of New York | Recruiting

Lawrence Honig, MD, PhD

New York, New York 10032
United States

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

Andrea Bozoki, MD

Chapel Hill, North Carolina 27599
United States

VIB-KU Leuven Center for Brain & Disease Research | Recruiting

Philip Van Damme, MD, PhD

Leuven, Flemish Brabankt 3000

CHU Lille - CMRR Hôpital Roger Salengro | Recruiting

Florence Pasquier, MD, PhD

Lille 59037

CHU Dupuytren, Limoges | Recruiting

Philippe Couratier, MD, PhD

Limoges 87042

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

Richard Levy, MD, PhD

Paris 75013

Universitaetsklinikum Ulm - Klinik fuer Neurologie | Recruiting

Albert C Ludolph, MD

Ulm, Baden-Wuerttemberg 89081

Complejo Hospitalario Universitario de Santiago (CHUS) | Recruiting

Julio Pardo Fernandez, MD, PhD

Santiago de Compostela, A Coruña 15706ES

Hospital de la Santa Creu i Sant Pau | Recruiting

Alberto Lleo Bisa, MD, PhD

Barcelona 08025

Hospital Universitario Vall d'Hebron | Recruiting

Raul Juntas Morales, MD

Barcelona 08035ES

Hospital Universitari I Politècnic La Fe | Recruiting

Miquel Baquero Toledo, MD

Valencia 46026