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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04993755
• Other study ID #: TPN-101-C9-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 1, 2021
• Est. completion date: September 1, 2023

Study information

• Verified date: March 2023
• Source: Transposon Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: September 1, 2023
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Aphasia, Primary Progressive
• Dementia
• Frontotemporal Dementia
• Motor Neuron Disease
• Pick Disease of the Brain
• Sclerosis

Intervention

Drug:
• TPN-101, 400 mg/day
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).
• Placebo
Placebo once daily for 24 weeks (double-blind treatment) followed by 400 mg/day TPN-101 for 24 weeks (open-label treatment).

Locations

Country	Name	City	State
Belgium	VIB-KU Leuven Center for Brain & Disease Research	Leuven	Flemish Brabankt
France	CHU Lille - CMRR Hôpital Roger Salengro	Lille
France	CHU Dupuytren, Limoges	Limoges
France	Groupe Hospitalier Pitie-Salpetriere - La Federation de Maladies du Systeme Nerveux	Paris
Germany	Universitaetsklinikum Ulm - Klinik fuer Neurologie	Ulm	Baden-Wuerttemberg
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Complejo Hospitalario Universitario de Santiago (CHUS)	Santiago de Compostela	A Coruña
Spain	Hospital Universitari I Politècnic La Fe	Valencia
United States	John Hopkins University	Baltimore	Maryland
United States	Johns Hopkins Outpatient Center	Baltimore	Maryland
United States	Massachusetts General Hospital (MGH) - Amyotrophic Lateral Sclerosis (ALS) Multidisciplinary Clinic	Boston	Massachusetts
United States	The University of North Carolina at Chapel Hill, Department of Neurology	Chapel Hill	North Carolina
United States	University of California San Diego	La Jolla	California
United States	Columbia University Medical Center - The Neurological Institute of New York	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	University of California Irvine - ALS & Neuromuscular Center	Orange	California
United States	Mayo Family Clinic Northwest	Rochester	Minnesota
United States	UCSF Neurosciences Clinical Research Unit (NCRU)	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Transposon Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)	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 C9ORF72 ALS/FTD	48 weeks
Secondary	Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)		48 weeks
Secondary	Assess the pharmacodynamic effect of TPN-101 on neurodegeneration as measured by changes in the levels of CSF and blood neurofilament light (NfL)		48 weeks
Secondary	Assess the clinical effect of TPN-101 as measured by changes in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)	The ALSFRS-R measures speech, salivation, swallowing, handwriting, cutting food and handling utensils (with or without gastrostomy), dressing and hygiene, turning in bed and adjusting bed clothes, walking, climbing, stairs, and breathing. Scores range from 0 to 40, with higher scores indicating that more function is retained.	48 weeks