Clinical trial NCT05152914: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neuronal Ceroid Lipofuscinosis Type 2
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
First posted: 2021-12-10
Enrollment: 5
Sex: ALL
Minimum age (years): 24
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Monitoring for the development of unacceptable toxicity.
timeFrame: 2 years
Secondary outcomes:
measure: Efficacy of intravitreal cerliponase alfa to stabilize fundoscopic features.
timeFrame: 2 years
measure: Efficacy of intravitreal cerliponase alfa to stabilize retinal architecture.
timeFrame: 2 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Nationwide Children's Hospital
name: David Rogers, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.