Clinical trial NCT04993755: A Phase 2a Study of TPN-101 in Patients With C9ORF72 ALS/FTD
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Keywords: ALS
FTD
Lead sponsor: Transposon Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)
timeFrame: 48 weeks
Secondary outcomes:
measure: Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)
timeFrame: 48 weeks
measure: Assess the pharmacodynamic effect of TPN-101 on neurodegeneration as measured by changes in the levels of CSF and blood neurofilament light (NfL)
timeFrame: 48 weeks
measure: Assess the clinical effect of TPN-101 as measured by changes in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
timeFrame: 48 weeks
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Orange
country: United States
facility: University of California Irvine - ALS & Neuromuscular Center
state: California
city: San Francisco
country: United States
facility: UCSF Neurosciences Clinical Research Unit (NCRU)
state: California
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) - Amyotrophic Lateral Sclerosis (ALS) Multidisciplinary Clinic
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Family Clinic Northwest
state: Minnesota
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - The Neurological Institute of New York
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill, Department of Neurology
state: North Carolina
city: Leuven
country: Belgium
facility: VIB-KU Leuven Center for Brain & Disease Research
state: Flemish Brabankt
city: Lille
country: France
facility: CHU Lille - CMRR Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU Dupuytren, Limoges
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere - La Federation de Maladies du Systeme Nerveux
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm - Klinik fuer Neurologie
state: Baden-Wuerttemberg
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
state: A Coruña
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Valencia
country: Spain
facility: Hospital Universitari I Politècnic La Fe
Study officials:
References: