Back to resultsAn Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of CLN3 Disease
Primary Purpose
Batten Disease
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Miglustat 100Mg Oral Capsule
Sponsored by
About this trial
This is an interventional treatment trial for Batten Disease focused on measuring Batten disease, CLN3, treatment, miglustat, safety
Eligibility Criteria
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
Sites / Locations
- Texas Children Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Oral miglustat
Arm Description
The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)
Outcomes
Primary Outcome Measures
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
AEs will be assessed by CTCAE v5
Secondary Outcome Measures
Miglustat PK
maximum plasma concentration Cmax
Miglustat PK
Time of Maximum concentration observedT max
Miglustat PK
Area under the plasma concentration versus time curve AUC
Miglustat PK
half life
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.
Clinical efficacy based on Vineland score
Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160
Clinical efficacy with the seizure frequency
seizure frequency will be assessed using a seizure diary
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
Clinical efficacy with MRI
MRI assessments to measure any grey matter atrophy due to neuronal loss
Full Information
NCT ID
NCT05174039
First Posted
November 18, 2021
Last Updated
September 15, 2022
Sponsor
Beyond Batten Disease Foundation
Collaborators
Theranexus
1. Study Identification
Unique Protocol Identification Number
NCT05174039
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2, 2022 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beyond Batten Disease Foundation
Collaborators
Theranexus
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Batten Disease
Keywords
Batten disease, CLN3, treatment, miglustat, safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Oral miglustat
Arm Type
Experimental
Arm Description
The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)
Intervention Type
Drug
Intervention Name(s)
Miglustat 100Mg Oral Capsule
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
AEs will be assessed by CTCAE v5
Time Frame
104 weeks
Secondary Outcome Measure Information:
Title
Miglustat PK
Description
maximum plasma concentration Cmax
Time Frame
18 weeks
Title
Miglustat PK
Description
Time of Maximum concentration observedT max
Time Frame
18 weeks
Title
Miglustat PK
Description
Area under the plasma concentration versus time curve AUC
Time Frame
18 weeks
Title
Miglustat PK
Description
half life
Time Frame
18 weeks
Title
Clinical efficacy based on UBDRS score
Description
Unified Battend Disease Rate Score (UBDRS) : minimum value : 8 and maximum values : 242. Higher scores means a worse outcome.
Time Frame
104 weeks
Title
Clinical efficacy based on Vineland score
Description
Vineland scale, higher score meaning a better outcome. Score minimal : 20 and score maximal is 160
Time Frame
104 weeks
Title
Clinical efficacy with the seizure frequency
Description
seizure frequency will be assessed using a seizure diary
Time Frame
104 weeks
Title
Clinical efficacy with ophtalmic assessment
Description
optical coherence tomography (OCT) will measure the retinal thickness to evaluate changes in retinal morphology and visual acuity in the patients
Time Frame
104 weeks
Title
Clinical efficacy with MRI
Description
MRI assessments to measure any grey matter atrophy due to neuronal loss
Time Frame
104 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Texas Children Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://beyondbatten.org
Description
Related Info
Learn more about this trial
An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of CLN3 Disease
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