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

NCT04993755 | Unknown Phase 2 FDA Drug

• 1 other identifier: TPN-101-C9-201
• Study Type: interventional
• Target: 42
• Locations: 5 countries
• Sites: 19

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).

Conditions

Amyotrophic Lateral Sclerosis; Frontotemporal Dementia

Keywords

ALS; FTD

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

TPN-101, 400 mg/day

EXPERIMENTAL

Drug: TPN-101, 400 mg/day

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

TPN-101, 400 mg/day 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).

TPN-101, 400 mg/day

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Transposon Therapeutics, Inc.: lead

Study Sites (19)

University of California San Diego

La Jolla, California, 92037, United States

Location

University of California Irvine - ALS & Neuromuscular Center

Orange, California, 92868, United States

Location

UCSF Neurosciences Clinical Research Unit (NCRU)

San Francisco, California, 94158, United States

Location

John Hopkins University

Baltimore, Maryland, 21287, United States

Location

Johns Hopkins Outpatient Center

Baltimore, Maryland, 21287, United States

Location

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

Boston, Massachusetts, 02114, United States

Location

Mayo Family Clinic Northwest

Rochester, Minnesota, 55905, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University Medical Center - The Neurological Institute of New York

New York, New York, 10032, United States

Location

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

Chapel Hill, North Carolina, 27599, United States

Location

VIB-KU Leuven Center for Brain & Disease Research

Leuven, Flemish Brabankt, 3000, Belgium

Location

CHU Lille - CMRR Hôpital Roger Salengro

Lille, 59037, France

Location

CHU Dupuytren, Limoges

Limoges, 87042, France

Location

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

Paris, 75013, France

Location

Universitaetsklinikum Ulm - Klinik fuer Neurologie

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, A Coruña, 15706ES, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035ES, Spain

Location

Hospital Universitari I Politècnic La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 6, 2021
• Study Start: October 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: March 6, 2023

Record last verified: 2023-03

Locations

US (10); BE (1); ES (4); FR (3); DE (1)