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

Transposon Therapeutics

Status and phase

Active, not recruiting

Phase 2

Conditions

Frontotemporal Dementia

Amyotrophic Lateral Sclerosis

Treatments

Drug: TPN-101, 400 mg/day

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT04993755

TPN-101-C9-201

Details and patient eligibility

About

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).

Full 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.

Enrollment

42 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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