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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04993755
Recruitment Status : Recruiting
First Posted : August 6, 2021
Last Update Posted : December 3, 2021
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Frontotemporal Dementia Drug: TPN-101, 400 mg/day Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 1, 2021
Estimated Primary Completion Date : September 1, 2023
Estimated Study Completion Date : September 1, 2023


Arm Intervention/treatment
Experimental: TPN-101, 400 mg/day Drug: TPN-101, 400 mg/day
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).

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




Primary Outcome Measures :
  1. Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) [ Time Frame: 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 :
  1. Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF) [ Time Frame: 48 weeks ]
  2. Assess the pharmacodynamic effect of TPN-101 on neurodegeneration as measured by changes in the levels of CSF and blood neurofilament light (NfL) [ Time Frame: 48 weeks ]
  3. Assess the clinical effect of TPN-101 as measured by changes in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have documentation of a clinical genetic test demonstrating the presence of a confirmed repeat expansion in the C9orf72 gene from a CLIA certified laboratory
  • Score ≥ 18 on the Mini-Mental State Exam (MMSE) at Screening
  • Have a reliable caregiver 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)
    • ALS Functional Rating Scale-Revised (ALSFRS-R) ≥ 30 at Screening
  • For patients with FTD:

    • A gradual, progressive decline in behavior, language, or motor function consistent with C9ORF72 hexanucleotide expansion-related syndrome such as behavioral variant FTD, primary progressive vaphasia, 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 significant brain abnormality, including, but not limited to, prior hemorrhage or infarct, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor such as meningioma); symptoms or signs of elevated intracranial pressure, e.g., symptoms or history of head injury or abnormal funduscopic exam. If there is history or evidence on neurologic exam suggesting possible subdural hematoma (SDH), patients should be fully evaluated, including magnetic resonance imaging (MRI) if indicated, to exclude significant, new SDH

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04993755


Contacts
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Contact: Jay Soto 310-261-5312 clinicaltrials@transposonrx.com

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: James Berry, MD, MPH         
Sponsors and Collaborators
Transposon Therapeutics, Inc.
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Responsible Party: Transposon Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04993755    
Other Study ID Numbers: TPN-101-C9-201
First Posted: August 6, 2021    Key Record Dates
Last Update Posted: December 3, 2021
Last Verified: December 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Transposon Therapeutics, Inc.:
ALS
FTD
Additional relevant MeSH terms:
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Dementia
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Sclerosis
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Neuromuscular Diseases
Spinal Cord Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Frontotemporal Lobar Degeneration
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations