An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of Subjects With Batten Ceroid Lipofuscinosis, Neuronal 3 (CLN3) Disease

An Open-label Safety, Pharmacokinetic, and Efficacy Study of the Combination of Miglustat for the Treatment of CLN3 Disease in Patients 17 Years of Age and Older

This is an open label study in approximately 6 subjects in 2 centers to assess the safety, PK, and efficacy of the maximum tolerable dose (MTD) of oral miglustat (100 mg once daily [QD] to 200 mg 3 times daily [TID]) in subjects ≥ 17 years of age with CLN3 disease over a period of 104 weeks.

Study Overview

• Status: Completed
• Conditions: Batten Disease
• Intervention / Treatment: Drug: Miglustat 100 milligrams (mg) Oral Capsule

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Individuals

1. Have provided informed consents (TCH and NIH) by subject or parent/legal guardian/legally authorized representative (as appropriate).
2. Are males or females ≥ 17 years of age at the time of screening

3. Have genetically confirmed diagnosis of syndromic CLN3 disease with

   EITHER:

   A. Two pathogenic mutations in the CLN3 gene, OR B. One confirmed pathogenic AND one variant of unknown significance, OR 2 variants of unknown significance, PLUS (+) secondary confirmation with evidence of characteristic inclusions on electron microscopy AND characteristic clinical course. There is no restriction on the specific CLN3 mutations for eligibility to enroll in the study. The mutations will be recorded in the electronic case report form (eCRF) for potential use in determining if CLN3 genotype is associated with tolerability and/or effectiveness of Beyond Batten Disease Foundation-1 (BBDF-1) (miglustat) therapy.

4. Male and female participants must use a highly effective method of contraception and must continue for the duration of the trial (and for 30 days after the end of treatment).
5. Are able to complete study assessments (subject or caregiver) and return to the clinic as scheduled

Exclusion criteria

Individuals

1. Have a medical condition that in the opinion of the PI would interfere with the safety assessments or increase the subject's risk of adverse events (AEs)
2. Use of any therapy (approved, off-label, or unapproved) intended to modify the course of any neuronal ceroid lipofuscinosis disease, including but not limited to flupirtine or flupirtine derivatives, cerliponase alfa (Brineura)
3. Have, in the opinion of the PI, a clinically significant abnormality in their clinical laboratory values (hematology, chemistry, or urinalysis) at screening that would preclude their participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral miglustat; The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)	Drug: Miglustat 100 milligrams (mg) Oral Capsule; Subjects will initiate miglustat at Week 1 and dosing will be escalated until 600mg/d. If a subject has not reached the maximum dose (600 mg/d) by Week 8, the Week 8 dose will be subject's MTD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment-emergent Adverse Events.	Number of treatment-emergent adverse events (TEAEs) assessed at all visits and phone calls, with severity classified according to CTCAE v5.0	78 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Miglustat Pharmacokinetic (PK) Parameter Cmax	Maximum plasma concentration Cmax	8 weeks
Miglustat PK Parameter Tmax	Time of Maximum concentration observed T max	8 weeks
Miglustat PK Parameter Area Under Curve (AUC)	Area under the plasma concentration versus time curve Area Under Curve from pre-administration to 8 hours post-administration (AUC0-8hour). Blood draws were taken at the following time points: pre-miglustat dose (0), 1, 2, 2.5, 3, 4, 6, and 8 hours after 8 weeks of treatment.	8 weeks
Miglustat PK Parameter T1/2	Miglustat elimination half life T1/2	8 weeks
Clinical Efficacy Based on Unified Batten Disease Rating Scale Subscores	Change from baseline of the modified Unified Batten Disease Rating Scale (UBDRS) Physical Assessment subscale (score from 0 to 112), specifically developed to assess motor symptoms in subjects with Batten Ceroid Lipofuscinosis, Neuronal 3 (CLN3) disease. Higher scores indicate more severe disease.	78 weeks
Clinical Efficacy With the Seizure Frequency	Seizure frequency were to be assessed using a seizure diary	78 weeks

Collaborators and Investigators

• Sponsor: Beyond Batten Disease Foundation
• Collaborators: Theranexus
• Investigators: Principal Investigator: Gary D. Clark, MD, Texas Children Hospital; Principal Investigator: An N. Dang Do, MD, PhD, National Institute of Health Clinical Center

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Actual): May 30, 2024
• Study Completion (Actual): May 30, 2024

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 30, 2021

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: treatment; safety; Batten disease; CLN3; miglustat
• Additional Relevant MeSH Terms: Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Neuronal Ceroid-Lipofuscinoses; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Glycoside Hydrolase Inhibitors; Miglustat
• Other Study ID Numbers: Batten-1-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No