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

Phase 1

Completed

• Conditions: Batten Disease
• Interventions: Drug: Miglustat 100 milligrams (mg) Oral Capsule

• Registration Number: NCT05174039
• Lead Sponsor: Beyond Batten Disease Foundation

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-18
• Study First Submitted QC: 2021-12-13
• Study First Posted: 2021-12-30
• Study Start: 2022-03-10
• Primary Completion: 2024-05-30
• Study Completion: 2024-05-30
• Status Verified: 2025-07
• Results First Submitted: 2025-07-04
• Results First Submitted QC: 2025-08-19
• Last Update Submitted: 2025-08-19
• Results First Posted: 2025-09-09
• Last Update Posted: 2025-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Oral miglustat	Miglustat 100 milligrams (mg) Oral Capsule	The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Miglustat PK Parameter Tmax	8 weeks	Time of Maximum concentration observed T max
Miglustat PK Parameter Area Under Curve (AUC)	8 weeks	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.
Miglustat PK Parameter T1/2	8 weeks	Miglustat elimination half life T1/2
Miglustat Pharmacokinetic (PK) Parameter Cmax	8 weeks	Maximum plasma concentration Cmax
Clinical Efficacy Based on Unified Batten Disease Rating Scale Subscores	78 weeks	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.
Clinical Efficacy With the Seizure Frequency	78 weeks	Seizure frequency were to be assessed using a seizure diary

Trial Locations

Locations (1)

Texas Children Hospital; 🇺🇸 Houston, Texas, United States