An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of CLN3 Disease

Batten Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05174039
• Other study ID #: Batten-1-01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 2, 2022
• Est. completion date: August 15, 2024

Study information

• Verified date: April 2024
• Source: Beyond Batten Disease Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. completion date: August 15, 2024
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 17 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Batten Disease
• Neuronal Ceroid-Lipofuscinoses

Intervention

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.

Locations

Country	Name	City	State
United States	Texas Children Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Beyond Batten Disease Foundation	Theranexus

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	AEs will be assessed by CTCAE v5	78 weeks
Secondary	Miglustat PK	maximum plasma concentration Cmax	18 weeks
Secondary	Miglustat PK	Time of Maximum concentration observedT max	18 weeks
Secondary	Miglustat PK	Area under the plasma concentration versus time curve AUC	18 weeks
Secondary	Miglustat PK	half life	18 weeks
Secondary	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
Secondary	Clinical efficacy based on Vineland score	Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160	78 weeks
Secondary	Clinical efficacy with the seizure frequency	seizure frequency will be assessed using a seizure diary	78 weeks
Secondary	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

External Links

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