CLN3Phase 1/2NCT03770572
Gene Therapy for Children With CLN3 Batten Disease
A Phase 1/2 study testing Low dose CLN-301 and High dose CLN-301 in people with CLN3 and Batten Disease, run by Neela Therapeutics at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 10 years
- Conditions the study is for
- CLN3, Batten Disease
- What is being tested?
- Low dose CLN-301 and High dose CLN-301
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Nov 2018to 30 Sep 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
- Aged ≥ 3 to < 11 years
- UBDRS physical impairment score of ≤ 7
- Able to walk independently at least 50 feet
Who cannot join
- 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)
- Presence of another neurological illness that may have caused cognitive decline (eg, trauma, meningitis, hemorrhage) before screening
- Active viral infection (includes HIV or serology positive for hepatitis B or C)
- 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)
- Subjects with anti-AAV9 antibody titers > 1:400 as determined by ELISA (enzyme-linked immunosorbent assay) binding immunoassay
- Abnormal laboratory values considered clinically significant
Show all 21Show fewer
- Presence of immunologic disease
- Has received stem cell or bone marrow transplantation
- Has received any form of organ transplant
- 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)
- Current use of cannabinoids and any by-products
- 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)
- Contraindications for MRI scans (eg, cardiac pacemaker, metal fragment or chip in the eye, aneurysm clip in the brain)
- Poorly controlled seizures - intractable epilepsy
- Episode of generalized motor status epilepticus within 4 weeks before the Gene Transfer visit
- History of corneal or intraocular surgery
- Severe infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, or meningitis) within 4 weeks before the Gene Transfer visit (Enrollment may be postponed.)
- Has received any investigational medication within 30 days before the infusion of study drug
- 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
- Pregnancy at screening or Day 0. Any female subject judged by the investigator to be of childbearing potential will be tested for pregnancy.
- Family does not want to disclose subject's study participation with primary care physician and other medical providers
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43201
About this study
Official title: Phase I/IIa Gene Transfer Clinical Trial for Juvenile Neuronal Ceroid Lipofuscinosis, Delivering the CLN3 Gene by Self-Complementary AAV9
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.
Read the detailed description
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 Neela Therapeutics at info@neelatx.com
- Conditions
- CLN3, Batten Disease
- Being tested
- Low dose CLN-301, High dose CLN-301
- Keywords
- CLN3, Neuronal ceroid lipofuscinosis, NCL, Gene Transfer
- Medical subject headings
- Neuronal Ceroid-Lipofuscinoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low dose CLN-301Genetic
Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at low dose
High dose CLN-301Genetic
Subjects with diagnosis of CLN3 Batten disease will receive a single dose of CLN-301 at high dose
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: CLN-301 Low-Dose | Experimental | No more than 5 mL of 6 x 1013 vg CLN-301 administered via intrathecal injection Receives: Genetic: Low dose CLN-301 |
| Cohort 2: CLN-301 High-Dose | Experimental | No more than 10 mL of 1.2 x 1014 vg of CLN-301 administered via intrathecal injection Receives: Genetic: High dose CLN-301 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety evaluation based on the development of dose-limiting toxicity (DLT).
The DLT is defined as any unanticipated AE that is considered related to CLN-301 and is Common Terminology Criteria for Adverse Events Grade 3 or higher.
Measured: 36 Months
Efficacy: Change in rating as determined using the Unified Batten Disease Rating Scale (UBDRS) rating scale.
The UBDRS is a clinical ratings instrument used specifically to assess motor, seizure, behavioral and functional capabilities. The "Physical Assessment" is a 20 item subscale that measures vision, speech, motor strength, gait, abnormal involuntary movements and balance. Each item has a score range of 0 to 4. The minimum score is 0 and the maximum score is 112. The items are summed up to obtain a total score.The higher the score, the more severe the disability and worse the outcome.
Measured: 36 months
Secondary outcomes (3)
QOL: Change in Quality of Life (QOL) as determined using the Pediatric Quality of Life (PedsQL™) scale.
The PedsQL is used to assess physical, emotional, social, and school functioning of pediatric subjects in ranging from 2 years to 18 years of age.
Measured: 36 months
Seizures: Change is seizure subscore as determined using Seizure subscale of the UBDRS scale.
The UBDRS seizure subscale is used to assess seizure history, type, frequency, duration, and frequency of seizure-related injury.
Measured: 36 months
Global impression: Change in disease severity using the UBDRS clinical global impression (CGI) subscale.
The clinical global impression subscale includes assessment of motor, seizure, behavioral and cognitive function in NCL subjects.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start13 Nov 2018
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for CLN3Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 7 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neela Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kathrin C Meyer, PhD, Principal investigator, Neela Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03770572
- Sponsor's protocol ID
- CLN-301
- Status last verified
- Aug 2025
- First submitted
- 7 Dec 2018
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23602993Phillips 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.
PubMed 15657902Munroe 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.
PubMed 9311735Drack 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.
PubMed 24547931Kwon 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.
PubMed 22013180Adams 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.
PubMed 24014508Ostergaard 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.
PubMed 21464428Cotman 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.
PubMed 12374761Johnson 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.
PubMed 37035740