Intravitreal ERT to Prevent Retinal Disease Progression in Children With CLN2

NCT ID: NCT05152914

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2027-11-01

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.

Conditions

Neuronal Ceroid Lipofuscinosis Type 2

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

Group Type: EXPERIMENTAL

Cerliponase Alfa

Intervention Type: DRUG

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.

Interventions

Cerliponase Alfa

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.

Intervention Type: DRUG

Other Intervention Names

Brineura

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

• Minimum Eligible Age: 24 Months
• Maximum Eligible Age: 72 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

David L Rogers, MD

OTHER

Sponsor Role: lead

Responsible Party

David L Rogers, MD

Chief of the Department of Ophthalmology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David Rogers, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23602993 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9295267 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29688815 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31283065 (View on PubMed)

Other Identifiers

STUDY00001444

Identifier Type: -

Identifier Source: org_study_id