An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of 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: Active, not recruiting
• Conditions: Batten Disease
• Intervention / Treatment: Drug: Miglustat 100Mg 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 BBDF-101 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 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 100Mg 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 participants with treatment-related adverse events as assessed by CTCAE v5.0	AEs will be assessed by CTCAE v5	78 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Miglustat PK	maximum plasma concentration Cmax	18 weeks
Miglustat PK	Time of Maximum concentration observedT max	18 weeks
Miglustat PK	Area under the plasma concentration versus time curve AUC	18 weeks
Miglustat PK	half life	18 weeks
Clinical efficacy based on UBDRS score	Unified Battend Disease Rate Score (UBDRS) : minimum value : 8 and maximum values : 242. Higher scores means a worse outcome.	78 weeks
Clinical efficacy based on Vineland score	Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160	78 weeks
Clinical efficacy with the seizure frequency	seizure frequency will be assessed using a seizure diary	78 weeks
Clinical efficacy with ophtalmic assessment	optical coherence tomography (OCT) will measure the retinal thickness to evaluate changes in retinal morphology and visual acuity in the patients	78 weeks

Collaborators and Investigators

• Sponsor: Beyond Batten Disease Foundation
• Collaborators: Theranexus

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Estimated): May 15, 2024
• Study Completion (Estimated): August 15, 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): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: treatment; safety; Batten disease; CLN3; miglustat
• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Lipid Metabolism Disorders; Lipidoses; Lipid Metabolism, Inborn Errors; Neuronal Ceroid-Lipofuscinoses; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; 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