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: April 26, 2024
• Sponsor: Beyond Batten Disease Foundation
• Collaborator: Theranexus
• Information provided by (Responsible Party): Beyond Batten Disease Foundation

Tracking Information

• First Submitted Date: November 18, 2021
• First Posted Date: December 30, 2021
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: February 2, 2022
• Estimated Primary Completion Date: May 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 25, 2024)

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 78 weeks ]

AEs will be assessed by CTCAE v5

Original Primary Outcome Measures (submitted: December 13, 2021)

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

Current Secondary Outcome Measures (submitted: April 25, 2024)

• Miglustat PK [ Time Frame: 18 weeks ]
  maximum plasma concentration Cmax
• Miglustat PK [ Time Frame: 18 weeks ]
  Time of Maximum concentration observedT max
• Miglustat PK [ Time Frame: 18 weeks ]
  Area under the plasma concentration versus time curve AUC
• Miglustat PK [ Time Frame: 18 weeks ]
  half life
• Clinical efficacy based on UBDRS score [ Time Frame: 78 weeks ]
  Unified Battend Disease Rate Score (UBDRS) : minimum value : 8 and maximum values : 242. Higher scores means a worse outcome.
• Clinical efficacy based on Vineland score [ Time Frame: 78 weeks ]
  Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160
• Clinical efficacy with the seizure frequency [ Time Frame: 78 weeks ]
  seizure frequency will be assessed using a seizure diary
• Clinical efficacy with ophtalmic assessment [ Time Frame: 78 weeks ]
  optical coherence tomography (OCT) will measure the retinal thickness to evaluate changes in retinal morphology and visual acuity in the patients

Original Secondary Outcome Measures (submitted: December 13, 2021)

• Miglustat and Trehalose PK [ Time Frame: 18 weeks ]
  maximum plasma concentration Cmax
• Miglustat and Trehalose PK [ Time Frame: 18 weeks ]
  Time of Maximum concentration observedT max
• Miglustat and Trehalose PK [ Time Frame: 18 weeks ]
  Area under the plasma concentration versus time curve AUC
• Miglustat and Trehalose PK [ Time Frame: 18 weeks ]
  half life
• 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.
• 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
• Clinical efficacy with the seizure frequency [ Time Frame: 104 weeks ]
  seizure frequency will be assessed using a seizure diary
• 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
• Clinical efficacy with MRI [ Time Frame: 104 weeks ]
  MRI assessments to measure any grey matter atrophy due to neuronal loss

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of CLN3 Disease
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Batten Disease

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.

Study Arms

Experimental: Oral miglustat

The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)

Intervention: Drug: Miglustat 100Mg Oral Capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 13, 2021): 6
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 15, 2024
• Estimated Primary Completion Date: May 15, 2024 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 17 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05174039
• Other Study ID Numbers: Batten-1-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Beyond Batten Disease Foundation
• Original Responsible Party: Same as current
• Current Study Sponsor: Beyond Batten Disease Foundation
• Original Study Sponsor: Same as current
• Collaborators: Theranexus
• Investigators: Not Provided
• PRS Account: Beyond Batten Disease Foundation
• Verification Date: April 2024