Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2

Study Overview
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Brief Summary
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This is a phase I/II randomized, masked, clinical trial to determine the safety and efficacy of intravitreal administration of cerliponase alfa.

Detailed Description
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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.

Official Title
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Intravitreal Enzyme Replacement Therapy to Prevent Retinal Disease Progression in Children With Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)

Conditions
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Neuronal Ceroid Lipofuscinosis Type 2

Intervention / Treatment
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* Drug: Cerliponase Alfa


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 24 Months
Maximum Age: 72 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br> | Drug: Cerliponase Alfa<br>* 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.<br>* Other names: Brineura;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 
| 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. | 2 years |