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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Batten Disease

Intervention / Treatment
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* Drug: Miglustat 100Mg Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals Have provided informed consents (TCH and NIH) by subject or parent/legal guardian/legally authorized representative (as appropriate). Are males or females ≥ 17 years of age at the time of screening 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. 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). Are able to complete study assessments (subject or caregiver) and return to the clinic as scheduled Exclusion criteria Individuals 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 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) 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

Ages Eligible for Study
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Minimum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral miglustat<br>The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID) | Drug: Miglustat 100Mg Oral Capsule<br>* 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.<br>|

What is the study measuring?
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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 | 104 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. | 104 weeks | 
| Clinical efficacy based on Vineland score | Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160 | 104 weeks | 
| Clinical efficacy with the seizure frequency | seizure frequency will be assessed using a seizure diary | 104 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 | 104 weeks | 
| Clinical efficacy with MRI | MRI assessments to measure any grey matter atrophy due to neuronal loss | 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Batten disease, CLN3, treatment, miglustat, safety