Gene Therapy for Children With CLN3 Batten Disease

NCT ID: NCT03770572

Last Updated: 2025-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-13

Study Completion Date

2029-09-30

Brief Summary

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This is a phase 1/2, open-label, single dose, dose-escalation clinical trial to evaluate the safety and efficacy of CLN-301 (previous NCH Code: scAAV9.P546.CLN3) delivered intrathecally into the lumbar spinal cord region of subjects with CLN3 Batten disease.

Detailed Description

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This is a phase 1/2, open-label, single-dose, dose-escalation study of CLN-301 administered intrathecally into the lumbar spinal cord region of pediatric patients with CLN3 Batten disease.

This study consists of a one-time injection of CLN-301 with follow-up visits on Day 7, 14, 21, and 30, followed by every 3 months through 1 year post-dose, and then every 6 months through the fifth year. There are two Cohorts with a low dose and a high dose.

The primary outcome for this clinical study is to evaluate safety. The co-primary objective is to determine the efficacy of CLN-301 as measured by United Batten Disease Rating Scale (UBDRS) physical subscale.

The secondary outcome measures include Pediatric Quality of Life (PedsQL) inventory, seizure subscale of the UBDRS and global impression subscale of the UBDRS.

The exploratory outcome measures include visual impairment assessment, cognitive evaluations, Brain magnetic resonance imaging (MRI), electroencephalogram (EEG), electrocardiogram (ECG) and echocardiogram (ECHO).

For more information about this study, please contact Alcyone Therapeutics at [email protected]

Conditions

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CLN3 Batten Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Single Treatment Group (AAV9-CLN3) - 2 Cohort Assignment (Low-dose, High-dose)

Dose escalation in this study will begin with low-dose, determined to be the minimal efficacious dose as determined in non-clinical studies. Dose escalation to a high-dose (2x the minimally effective dose (MED) as evaluated in Cohort 1) will proceed as part of Cohort 2 of the study upon demonstration of safety of the low-dose in Cohort 1 of the study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1: CLN-301 Low-Dose

No more than 5 mL of 6 x 1013 vg CLN-301 administered via intrathecal injection

Group Type EXPERIMENTAL

Low dose CLN-301

Intervention Type GENETIC

Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at low dose

Cohort 2: CLN-301 High-Dose

No more than 10 mL of 1.2 x 1014 vg of CLN-301 administered via intrathecal injection

Group Type EXPERIMENTAL

High dose CLN-301

Intervention Type GENETIC

Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at high dose

Interventions

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Low dose CLN-301

Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at low dose

Intervention Type GENETIC

High dose CLN-301

Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at high dose

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis of CLN3 Batten disease determined by genotype available at screening by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified laboratory (or a non-US laboratory with an equivalent national accreditation/certification)
2. Aged ≥ 3 to \< 11 years
3. UBDRS physical impairment score of ≤ 7
4. Able to walk independently at least 50 feet

Exclusion Criteria

1. Presence of another inherited neurologic or metabolic disease, eg, other forms of Batten disease (also known as neuronal ceroid lipofuscinosis; NCL) or seizures unrelated to CLN3 Batten disease (subjects with febrile seizures may be eligible at the discretion of the investigator)
2. Presence of another neurological illness that may have caused cognitive decline (eg, trauma, meningitis, hemorrhage) before screening
3. Active viral infection (includes HIV or serology positive for hepatitis B or C)
4. Subjects with 2 consecutive aminotransaminase liver tests \> 3 times the upper limit of normal or \> 1.5 times the upper limit of normal if taking valproic acid at Visit 1 (screening/baseline)
5. Subjects with anti-AAV9 antibody titers \> 1:400 as determined by ELISA (enzyme-linked immunosorbent assay) binding immunoassay
6. Abnormal laboratory values considered clinically significant
7. Presence of immunologic disease
8. Has received stem cell or bone marrow transplantation
9. Has received any form of organ transplant
10. 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 investigator)
11. Current use of cannabinoids and any by-products
12. Contraindications for intrathecal administration of the product or lumbar puncture (for collection of CSF), such as bleeding disorders or other medical conditions (eg, spina bifida, meningitis, or clotting abnormalities)
13. Contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
14. Poorly controlled seizures - intractable epilepsy
15. Episode of generalized motor status epilepticus within 4 weeks before the Gene Transfer visit
16. History of corneal or intraocular surgery
17. Severe infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the Gene Transfer visit (Enrollment may be postponed.)
18. Has received any investigational medication within 30 days before the infusion of study drug
19. 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
20. Pregnancy at screening or Day 0. Any female subject judged by the investigator to be of childbearing potential will be tested for pregnancy.
21. Family does not want to disclose subject's study participation with primary care physician and other medical providers
Minimum Eligible Age

3 Years

Maximum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alcyone Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kathrin C Meyer, PhD

Role: PRINCIPAL_INVESTIGATOR

Alcyone Therapeutics

Locations

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Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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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)

Phillips SN, Benedict JW, Weimer JM, Pearce DA. CLN3, the protein associated with batten disease: structure, function and localization. J Neurosci Res. 2005 Mar 1;79(5):573-83. doi: 10.1002/jnr.20367.

Reference Type BACKGROUND
PMID: 15657902 (View on PubMed)

Munroe PB, Mitchison HM, O'Rawe AM, Anderson JW, Boustany RM, Lerner TJ, Taschner PE, de Vos N, Breuning MH, Gardiner RM, Mole SE. Spectrum of mutations in the Batten disease gene, CLN3. Am J Hum Genet. 1997 Aug;61(2):310-6. doi: 10.1086/514846.

Reference Type BACKGROUND
PMID: 9311735 (View on PubMed)

Drack AV, Mullins RF, Pfeifer WL, Augustine EF, Stasheff SF, Hong SD. Immunosuppressive Treatment for Retinal Degeneration in Juvenile Neuronal Ceroid Lipofuscinosis (Juvenile Batten Disease). Ophthalmic Genet. 2015;36(4):359-64. doi: 10.3109/13816810.2014.886271. Epub 2014 Feb 19.

Reference Type BACKGROUND
PMID: 24547931 (View on PubMed)

Kwon JM, Adams H, Rothberg PG, Augustine EF, Marshall FJ, Deblieck EA, Vierhile A, Beck CA, Newhouse NJ, Cialone J, Levy E, Ramirez-Montealegre D, Dure LS, Rose KR, Mink JW. Quantifying physical decline in juvenile neuronal ceroid lipofuscinosis (Batten disease). Neurology. 2011 Nov 15;77(20):1801-7. doi: 10.1212/WNL.0b013e318237f649. Epub 2011 Oct 19.

Reference Type BACKGROUND
PMID: 22013180 (View on PubMed)

Adams HR, Mink JW; University of Rochester Batten Center Study Group. Neurobehavioral features and natural history of juvenile neuronal ceroid lipofuscinosis (Batten disease). J Child Neurol. 2013 Sep;28(9):1128-36. doi: 10.1177/0883073813494813.

Reference Type BACKGROUND
PMID: 24014508 (View on PubMed)

Ostergaard JR, Rasmussen TB, Molgaard H. Cardiac involvement in juvenile neuronal ceroid lipofuscinosis (Batten disease). Neurology. 2011 Apr 5;76(14):1245-51. doi: 10.1212/WNL.0b013e31821435bd.

Reference Type BACKGROUND
PMID: 21464428 (View on PubMed)

Cotman SL, Vrbanac V, Lebel LA, Lee RL, Johnson KA, Donahue LR, Teed AM, Antonellis K, Bronson RT, Lerner TJ, MacDonald ME. Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth. Hum Mol Genet. 2002 Oct 15;11(22):2709-21. doi: 10.1093/hmg/11.22.2709.

Reference Type BACKGROUND
PMID: 12374761 (View on PubMed)

Johnson TB, Brudvig JJ, Likhite S, Pratt MA, White KA, Cain JT, Booth CD, Timm DJ, Davis SS, Meyerink B, Pineda R, Dennys-Rivers C, Kaspar BK, Meyer K, Weimer JM. Early postnatal administration of an AAV9 gene therapy is safe and efficacious in CLN3 disease. Front Genet. 2023 Mar 24;14:1118649. doi: 10.3389/fgene.2023.1118649. eCollection 2023.

Reference Type DERIVED
PMID: 37035740 (View on PubMed)

Other Identifiers

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CLN-301

Identifier Type: -

Identifier Source: org_study_id

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