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).
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.
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