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

• ClinicalTrials.gov Identifier: NCT05174039
• Recruitment Status: Active, not recruiting
• First Posted: December 30, 2021
• Last Update Posted: September 16, 2022
• Sponsor: Beyond Batten Disease Foundation
• Collaborator: Theranexus
• Information provided by (Responsible Party): Beyond Batten Disease Foundation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Batten Disease	Drug: Miglustat 100Mg Oral Capsule	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 2, 2022
• Estimated Primary Completion Date: September 2024
• Estimated Study Completion Date: October 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 104 weeks ]
   AEs will be assessed by CTCAE v5

Secondary Outcome Measures :

1. Miglustat PK [ Time Frame: 18 weeks ]
   maximum plasma concentration Cmax
2. Miglustat PK [ Time Frame: 18 weeks ]
   Time of Maximum concentration observedT max
3. Miglustat PK [ Time Frame: 18 weeks ]
   Area under the plasma concentration versus time curve AUC
4. Miglustat PK [ Time Frame: 18 weeks ]
   half life
5. Clinical efficacy based on UBDRS score [ Time Frame: 104 weeks ]
   Unified Battend Disease Rate Score (UBDRS) : minimum value : 8 and maximum values : 242. Higher scores means a worse outcome.
6. Clinical efficacy based on Vineland score [ Time Frame: 104 weeks ]
   Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160
7. Clinical efficacy with the seizure frequency [ Time Frame: 104 weeks ]
   seizure frequency will be assessed using a seizure diary
8. Clinical efficacy with ophtalmic assessment [ Time Frame: 104 weeks ]
   optical coherence tomography (OCT) will measure the retinal thickness to evaluate changes in retinal morphology and visual acuity in the patients
9. Clinical efficacy with MRI [ Time Frame: 104 weeks ]
   MRI assessments to measure any grey matter atrophy due to neuronal loss

Eligibility Criteria

• Ages Eligible for Study: 17 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

Texas Children Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Beyond Batten Disease Foundation

Theranexus

More Information

Additional Information:

Related Info 

• Responsible Party: Beyond Batten Disease Foundation
• ClinicalTrials.gov Identifier: NCT05174039
• Other Study ID Numbers: Batten-1-01
• First Posted: December 30, 2021
• Last Update Posted: September 16, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Beyond Batten Disease Foundation:

Batten disease; CLN3; treatment; miglustat; safety

Additional relevant MeSH terms:

Neuronal Ceroid-Lipofuscinoses; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Lipid Metabolism Disorders; Metabolic Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Miglustat; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Physiological Effects of Drugs