Back to resultsIntravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2
Primary Purpose
Neuronal Ceroid Lipofuscinosis Type 2
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cerliponase Alfa
Sponsored by
About this trial
This is an interventional treatment trial for Neuronal Ceroid Lipofuscinosis Type 2
Eligibility Criteria
Inclusion Criteria:
- Genotypic confirmation of classical CLN2 Batten's disease from a CLIA certified lab.
- Enzyme level deficiency of tripeptidyl-peptidase
- Minimum age requirement: 24 months of age at enrollment
- Maximum age requirement: 72 months of age at enrollment
- Currently receiving intraventricular cerliponase alfa
- Willing to participate in the proposed study visits over the 2-year period
- Minimum central retinal thickness (CRT) of 140μm based upon OCT assessment
- Clear ocular media
- No ocular pathology present to account for vision loss other than optic atrophy and pigmentary retinopathy that is felt to be due to the CLN2 disease process
Exclusion Criteria:
- Any opacities in the clear ocular media including vitreous debris.
- History of ocular trauma or prior ocular surgery.
- Episode of generalized motor status epilepticus within four weeks before the First Dose visit
- Severe infection (e.g., upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within four weeks before the First Dose visit (enrollment may be postponed)
- Those with a history of bleeding disorders.
- History of or current chemotherapy, radiotherapy or other immunosuppression therapy within the past 30 days (corticosteroid treatment may be permitted at the discretion of the PI)
- Has a medical condition, or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability
Sites / Locations
- Nationwide Children's Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Intervention
Arm Description
Outcomes
Primary Outcome Measures
Monitoring for the development of unacceptable toxicity.
Based on the development of unacceptable toxicity, defined as the occurrence of any Grade 3 or higher, unanticipated, treatment related toxicity.
Secondary Outcome Measures
Efficacy of intravitreal cerliponase alfa to stabilize fundoscopic features.
Efficacy will be determined by measuring the Weill Cornell LINCL Ophthalmic Severity Score prior to each injection.
Efficacy of intravitreal cerliponase alfa to stabilize retinal architecture.
Efficacy will be determined by measuring central retinal thickness via OCT imaging prior to each injection.
Full Information
NCT ID
NCT05152914
First Posted
November 29, 2021
Last Updated
September 11, 2023
Sponsor
David L Rogers, MD
1. Study Identification
Unique Protocol Identification Number
NCT05152914
Brief Title
Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2
Official Title
Intravitreal Enzyme Replacement Therapy to Prevent Retinal Disease Progression in Children With Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
November 1, 2025 (Anticipated)
Study Completion Date
November 1, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
David L Rogers, MD
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 a phase I/II randomized, masked, clinical trial to determine the safety and efficacy of intravitreal administration of cerliponase alfa.
Detailed Description
This is a Phase I/II study for 5 subjects receiving an intravitreal injection of cerliponase alfa under sedation into the proclaimed study eye(s) in a 4-week interval over 24 months. This study will be monitored by a Data Safety Monitoring Committee (DSMB). Each subject will participate in the ongoing study for an active period of 2 years. Subjects will then transfer to a bi-annual monitoring program where data will be collected from bi-annual standard of care visits for an additional 3 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuronal Ceroid Lipofuscinosis Type 2
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
5 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Cerliponase Alfa
Other Intervention Name(s)
Brineura
Intervention Description
Brineura is a hydrolytic lysosomal N-terminal tripeptidyl peptidase indicated to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency.
Primary Outcome Measure Information:
Title
Monitoring for the development of unacceptable toxicity.
Description
Based on the development of unacceptable toxicity, defined as the occurrence of any Grade 3 or higher, unanticipated, treatment related toxicity.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Efficacy of intravitreal cerliponase alfa to stabilize fundoscopic features.
Description
Efficacy will be determined by measuring the Weill Cornell LINCL Ophthalmic Severity Score prior to each injection.
Time Frame
2 years
Title
Efficacy of intravitreal cerliponase alfa to stabilize retinal architecture.
Description
Efficacy will be determined by measuring central retinal thickness via OCT imaging prior to each injection.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
24 Months
Maximum Age & Unit of Time
72 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Genotypic confirmation of classical CLN2 Batten's disease from a CLIA certified lab.
Enzyme level deficiency of tripeptidyl-peptidase
Minimum age requirement: 24 months of age at enrollment
Maximum age requirement: 72 months of age at enrollment
Currently receiving intraventricular cerliponase alfa
Willing to participate in the proposed study visits over the 2-year period
Minimum central retinal thickness (CRT) of 140μm based upon OCT assessment
Clear ocular media
No ocular pathology present to account for vision loss other than optic atrophy and pigmentary retinopathy that is felt to be due to the CLN2 disease process
Exclusion Criteria:
Any opacities in the clear ocular media including vitreous debris.
History of ocular trauma or prior ocular surgery.
Episode of generalized motor status epilepticus within four weeks before the First Dose visit
Severe infection (e.g., upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within four weeks before the First Dose visit (enrollment may be postponed)
Those with a history of bleeding disorders.
History of or current chemotherapy, radiotherapy or other immunosuppression therapy within the past 30 days (corticosteroid treatment may be permitted at the discretion of the PI)
Has a medical condition, or extenuating circumstance that, in the opinion of the investigator, might compromise the subject's ability to comply with the protocol required testing or procedures or compromise the subject's wellbeing, safety, or clinical interpretability
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Rogers, MD
Organizational Affiliation
Nationwide Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23602993
Citation
Schulz A, Kohlschutter A, Mink J, Simonati A, Williams R. NCL diseases - clinical perspectives. Biochim Biophys Acta. 2013 Nov;1832(11):1801-6. doi: 10.1016/j.bbadis.2013.04.008. Epub 2013 Apr 17.
Results Reference
background
PubMed Identifier
9295267
Citation
Sleat DE, Donnelly RJ, Lackland H, Liu CG, Sohar I, Pullarkat RK, Lobel P. Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. Science. 1997 Sep 19;277(5333):1802-5. doi: 10.1126/science.277.5333.1802.
Results Reference
background
PubMed Identifier
29688815
Citation
Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschutter A; CLN2 Study Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J Med. 2018 May 17;378(20):1898-1907. doi: 10.1056/NEJMoa1712649. Epub 2018 Apr 24.
Results Reference
background
PubMed Identifier
31283065
Citation
Gardner E, Bailey M, Schulz A, Aristorena M, Miller N, Mole SE. Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. Hum Mutat. 2019 Nov;40(11):1924-1938. doi: 10.1002/humu.23860. Epub 2019 Jul 26.
Results Reference
background
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Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2
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