A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD
- Conditions
- Amyotrophic Lateral SclerosisFrontotemporal Dementia
- Interventions
- Drug: TPN-101, 400 mg/dayDrug: Placebo
- Registration Number
- NCT04993755
- Lead Sponsor
- Transposon Therapeutics, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 42
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TPN-101, 400 mg/day TPN-101, 400 mg/day - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) 48 weeks 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
- Secondary Outcome Measures
Name Time Method Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF) 48 weeks 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 Assess the clinical effect of TPN-101 as measured by changes in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) 48 weeks 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.
Trial Locations
- Locations (19)
Massachusetts General Hospital (MGH) - Amyotrophic Lateral Sclerosis (ALS) Multidisciplinary Clinic
🇺🇸Boston, Massachusetts, United States
John Hopkins University
🇺🇸Baltimore, Maryland, United States
CHU Dupuytren, Limoges
🇫🇷Limoges, France
Hospital for Special Surgery
🇺🇸New York, New York, United States
CHU Lille - CMRR Hôpital Roger Salengro
🇫🇷Lille, France
Mayo Family Clinic Northwest
🇺🇸Rochester, Minnesota, United States
Universitaetsklinikum Ulm - Klinik fuer Neurologie
🇩🇪Ulm, Baden-Wuerttemberg, Germany
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
Hospital Universitari I Politècnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
University of California Irvine - ALS & Neuromuscular Center
🇺🇸Orange, California, United States
UCSF Neurosciences Clinical Research Unit (NCRU)
🇺🇸San Francisco, California, United States
Johns Hopkins Outpatient Center
🇺🇸Baltimore, Maryland, United States
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Groupe Hospitalier Pitie-Salpetriere - La Federation de Maladies du Systeme Nerveux
🇫🇷Paris, France
VIB-KU Leuven Center for Brain & Disease Research
🇧🇪Leuven, Flemish Brabankt, Belgium
Complejo Hospitalario Universitario de Santiago (CHUS)
🇪🇸Santiago de Compostela, A Coruña, Spain
University of California San Diego
🇺🇸La Jolla, California, United States