Clinical trial NCT05174039: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Batten Disease
Keywords: Batten disease
CLN3
treatment
miglustat
safety
Lead sponsor: Beyond Batten Disease Foundation
Sponsor class: OTHER
Collaborators: name: Theranexus
First posted: 2021-12-30
Enrollment: 6
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: 78 weeks
Secondary outcomes:
measure: Miglustat PK
timeFrame: 18 weeks
measure: Miglustat PK
timeFrame: 18 weeks
measure: Miglustat PK
timeFrame: 18 weeks
measure: Miglustat PK
timeFrame: 18 weeks
measure: Clinical efficacy based on UBDRS score
timeFrame: 78 weeks
measure: Clinical efficacy based on Vineland score
timeFrame: 78 weeks
measure: Clinical efficacy with the seizure frequency
timeFrame: 78 weeks
measure: Clinical efficacy with ophtalmic assessment
timeFrame: 78 weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: Texas Children Hospital
state: Texas
Study officials:
References: