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

Phase 1
Active, not recruiting
Conditions
Batten Disease
Interventions
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

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
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 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
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Oral miglustatMiglustat 100Mg Oral CapsuleThe proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)
Primary Outcome Measures
NameTimeMethod
Number of participants with treatment-related adverse events as assessed by CTCAE v5.078 weeks

AEs will be assessed by CTCAE v5

Secondary Outcome Measures
NameTimeMethod
Clinical efficacy with the seizure frequency78 weeks

seizure frequency will be assessed using a seizure diary

Clinical efficacy with ophtalmic assessment78 weeks

optical coherence tomography (OCT) will measure the retinal thickness to evaluate changes in retinal morphology and visual acuity in the patients

Miglustat PK18 weeks

half life

Clinical efficacy based on Vineland score78 weeks

Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160

Clinical efficacy based on UBDRS score78 weeks

Unified Battend Disease Rate Score (UBDRS) : minimum value : 8 and maximum values : 242. Higher scores means a worse outcome.

Trial Locations

Locations (1)

Texas Children Hospital

🇺🇸

Houston, Texas, United States

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