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

NCT ID: NCT04993755

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-01
• Study Completion Date: 2023-09-01

Brief 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).

Detailed 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.

Conditions

Amyotrophic Lateral Sclerosis; Frontotemporal Dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TPN-101, 400 mg/day

Group Type: EXPERIMENTAL

TPN-101, 400 mg/day

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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).

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Transposon Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California San Diego

La Jolla, California, United States

University of California Irvine - ALS & Neuromuscular Center

Orange, California, United States

UCSF Neurosciences Clinical Research Unit (NCRU)

San Francisco, California, 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

Mayo Family Clinic Northwest

Rochester, Minnesota, United States

Hospital for Special Surgery

New York, New York, United States

Columbia University Medical Center - The Neurological Institute of New York

New York, New York, United States

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

Chapel Hill, North Carolina, United States

VIB-KU Leuven Center for Brain & Disease Research

Leuven, Flemish Brabankt, Belgium

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, , France

Universitaetsklinikum Ulm - Klinik fuer Neurologie

Ulm, Baden-Wurttemberg, Germany

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, A Coruña, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital Universitari I Politècnic La Fe

Valencia, , Spain

Countries

United States; Belgium; France; Germany; Spain

Other Identifiers

TPN-101-C9-201

Identifier Type: -

Identifier Source: org_study_id