Neuronal Ceroid Lipofuscinosis CLN5Phase 1/2CLN5-200NCT05228145
Gene Therapy Study for Children With CLN5 Batten Disease
A Phase 1/2 study testing NGN-101 in people with Neuronal Ceroid Lipofuscinosis CLN5, run by Neurogene Inc. at 2 sites in 2 countries.
Trial summary
This is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with Neuronal Ceroid Lipofuscinosis (Batten) Subtype 5 (CLN5) disease. Read more about this study
- Who is it for?
- Ages 3 to 9 years
- Conditions the study is for
- Neuronal Ceroid Lipofuscinosis CLN5
- What is being tested?
- NGN-101
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 31 Jan 2022to Nov 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 9 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age from 3 to 9 years (Child)
- Molecular genetic diagnosis of the CLN5 gene
- Confirmed clinical diagnosis of CLN5 disease
- Impaired motor and/or language function and/or impaired visual acuity
- Written informed consent from parent or legal guardian and assent from study participant, if appropriate
- Able to comply with protocol required assessments (laboratory sample collection, lumbar puncture (LP), nerve conduction studies (NCS), magnetic resonance imaging (MRI), etc.), which may require sedation or general anesthesia
- Able to walk with or without assistance (assistance may include a walker, braces, or with one hand held)
- Agree to reside within a 1-hour drive of the study site for at least 6 months following treatment (or a safely drivable distance for the study participant and caregivers according to investigator's discretion)
Who cannot join
- Has another neurologic disease or illness that may have caused cognitive decline before study entry
- Known pathogenic or clinically suspected variant in a seizure associated genetic mutation besides CLN5
- Any active infections or severe infections within the 30 days prior to study treatment administration
- Presence of a concomitant medical condition that precludes intracerebroventricular (ICV) injection, lumbar puncture (LP), or use of anesthetics needed for study-related procedures
- Presence of any concomitant medical conditions that preclude intravitreal (IVT) administration
- Has status epilepticus that lasts longer than 5 minutes or having more than 1 seizure within a 5-minute period, without returning to a normal level of consciousness between episodes within 12 weeks before study treatment
Show all 17Show fewer
- Total anti-AAV9 antibody titer greater than 1:400
- Any anticipated need for major surgery in the next 24 months
- Participation in an Investigational New Drug, Investigational Device Exemption, or equivalent clinical study in the past 6 months
- Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
- Participation in other investigational studies and non-interventional studies that have similar study assessments as this protocol while the study participant is enrolled in this study with the exception of sister studies sponsored by Neurogene
- History of or current chemotherapy, radiotherapy, or other immunosuppressive therapy within the past 3 months
- Use of prohibited medications
- Immunizations of any kind in the 45 days prior to study treatment
- Requiring daytime or nighttime ventilatory support at the time of Screening
- Any item which would exclude the study participant from being able to undergo brain magnetic resonance imaging (MRI) according to local institutional policy
- Known allergies or hypersensitivities to the required immunosuppression regime
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United Kingdom1 site
Great Ormond Street Hospital for Children
London, WC1N 3JH
About this study
Official title: A Phase 1/2 Intracerebroventricular and Intravitreal Administration of NGN-101 for Treatment of Neuronal Ceroid Lipofuscinosis (NCL) Subtype 5 (CLN5) Disease
This is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with Neuronal Ceroid Lipofuscinosis (Batten) Subtype 5 (CLN5) disease.
Read the detailed description
The study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding human ceroid-lipofuscinosis neuronal protein 5 (CLN5) in subjects with CLN5 Batten disease. The study treatment will be delivered via intracerebroventricular (ICV) and intravitreal (IVT) injection on the same day. Each participant will be followed for safety and efficacy for 5 years after treatment. Efficacy assessments in this study will evaluate motor, language, visual and cognitive function.
- Conditions
- Neuronal Ceroid Lipofuscinosis CLN5
- Being tested
- NGN-101
- Keywords
- Batten Disease, Neuronal Ceroid Lipofuscinosis Disease, Neuronal Ceroid Lipofuscinosis Subtype 5 Disease, NCL, Gene Therapy, Gene Transfer, CLN5, CLN
- 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.
NGN-101Genetic
Participants with confirmed mutations in the CLN5 gene who meet all the inclusion and none of the exclusion criteria will be treated with a single intracerebroventricular (ICV) dose and a single intravitreal (IVT) dose of the study treatment.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt). Receives: Genetic: NGN-101 |
| Cohort 2 | Experimental | The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt). Receives: Genetic: NGN-101 |
| Cohort 3 | Experimental | The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt). Receives: Genetic: NGN-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment Emergent Adverse Events (TEAEs)
Incidence, type, severity, and frequency of TEAEs
Measured: 5 years (multiple visits)
Incidence of Serious Adverse Events (SAEs)
Incidence, type, severity, and frequency of SAEs
Measured: 5 years (multiple visits)
Incidence of clinical laboratory abnormalities
Incidence, type, severity, and frequency of clinical laboratory abnormalities
Measured: 5 years (multiple visits)
Incidence of new nerve conduction study (NCS) abnormalities
Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities
Measured: 5 years (multiple visits)
Incidence of new physical and neurologic exam abnormalities
Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
Measured: 5 years (multiple visits)
Secondary outcomes (6)
Change in Hamburg Scale, Motor and Language domain scores
Change from baseline in Hamburg Scale, Motor and Language domain scores (each domain is rated from 0 to 3, with 3 reflecting normal function for age and 0 reflecting complete loss of function)
Measured: 5 years (multiple visits)
Change in Spectral Domain-Optical Coherence Tomography (SD-OCT)
Change from baseline in SD-OCT parameters including Ellipsoid Zone (EZ) defect area measurements, macular volume and thickness, retinal nerve fiber layer thickness, and ganglion cell layer thickness
Measured: 5 years (multiple visits)
Change in Unified Batten Diseases Rating Scale (UBDRS)
Change from baseline in total score and individual domains of the Unified Batten Diseases Rating Scale (UBDRS; total score 0 to 277, with higher scores indicating worse function)
Measured: 5 years (multiple visits)
Change in Caregiver global impression of change
Caregiver global impression of change throughout the study
Measured: 5 years (multiple visits)
Change in visual acuity measurements
Change from baseline in visual acuity measured using Teller acuity cards, Lea symbol chart, Landolt C chart, or low contrast visual acuity (measure to be used will depend on subject's level of cognitive and visual function)
Measured: 5 years (multiple visits)
Change in color vision
Change from baseline in color vision measured using Ishihara color blindness testing
Measured: 5 years (multiple visits)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2022
- Study start31 Jan 2022
- Primary completionNov 2028 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neuronal Ceroid Lipofuscinosis CLN5Studies 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
- Sequential
- Model description
- Dose escalation cohort study of NGN-101 administered by intracerebroventricular (ICV) infusion and intravitreal (IVT) injection; cohorts will be assigned sequentially.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurogene Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Effie Albanis, MD, Study director, Neurogene Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05228145
- Sponsor's protocol ID
- CLN5-200
- Acronym
- CLN5-200
- Status last verified
- Aug 2024
- First submitted
- 17 Dec 2021
- Last updated
- 12 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Gray SJ, Palmer DN, Mitchell NL. Efficacy of dual intracerebroventricular and intravitreal CLN5 gene therapy in sheep prompts the first clinical trial to treat CLN5 Batten disease. Front Pharmacol. 2023 Oct 24;14:1212235. doi: 10.3389/fphar.2023.1212235. eCollection 2023.
PubMed 37942487Mitchell NL, Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Palmer MJ, Pulickan A, Prendergast PM, Casy W, Gray SJ, Palmer DN. Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease. Front Genet. 2023 Aug 8;14:1212228. doi: 10.3389/fgene.2023.1212228. eCollection 2023.
PubMed 37614821
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Intracerebroventricular and Intravitreal Administration of NGN-101 for Treatment of Neuronal Ceroid Lipofuscinosis (NCL) Subtype 5 (CLN5) Disease
- ClinicalTrials.gov ID
- NCT05228145
- Acronym / sponsor ID
- CLN5-200 / CLN5-200
- Conditions
- Neuronal Ceroid Lipofuscinosis CLN5
- Keywords
- Batten Disease, Neuronal Ceroid Lipofuscinosis Disease, Neuronal Ceroid Lipofuscinosis Subtype 5 Disease, NCL, Gene Therapy, Gene Transfer, CLN5, CLN
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Neurogene Inc.Industry (pharma, biotech, devices)
- Study start
- 31 Jan 2022 (actual)
- Primary completion
- Nov 2028 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 8 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, non-randomized, open-label, dose escalation study of a single administration of gene therapy in children who are 3 to 9 years old with Neuronal Ceroid Lipofuscinosis (Batten) Subtype 5 (CLN5) disease.
Detailed description
The study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding human ceroid-lipofuscinosis neuronal protein 5 (CLN5) in subjects with CLN5 Batten disease. The study treatment will be delivered via intracerebroventricular (ICV) and intravitreal (IVT) injection on the same day. Each participant will be followed for safety and efficacy for 5 years after treatment. Efficacy assessments in this study will evaluate motor, language, visual and cognitive function.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Dose escalation cohort study of NGN-101 administered by intracerebroventricular (ICV) infusion and intravitreal (IVT) injection; cohorts will be assigned sequentially.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Genetic: NGN-101The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt). |
| Cohort 2 | Experimental | Genetic: NGN-101The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt). |
| Cohort 3 | Experimental | Genetic: NGN-101The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt). |
Who may qualify
- Ages
- 3 to 9 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Age from 3 to 9 years (Child)
- Molecular genetic diagnosis of the CLN5 gene
- Confirmed clinical diagnosis of CLN5 disease
- Impaired motor and/or language function and/or impaired visual acuity
- Written informed consent from parent or legal guardian and assent from study participant, if appropriate
Key exclusion criteria (17 listed)
- Has another neurologic disease or illness that may have caused cognitive decline before study entry
- Known pathogenic or clinically suspected variant in a seizure associated genetic mutation besides CLN5
- Any active infections or severe infections within the 30 days prior to study treatment administration
- Presence of a concomitant medical condition that precludes intracerebroventricular (ICV) injection, lumbar puncture (LP), or use of anesthetics needed for study-related procedures
- Presence of any concomitant medical conditions that preclude intravitreal (IVT) administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGN-101Participants with confirmed mutations in the CLN5 gene who meet all the inclusion and none of the exclusion criteria will be treated with a single intracerebroventricular (ICV) dose and a single intravitreal (IVT) dose of the study treatment. | Genetic | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time frame: 5 years (multiple visits)
Incidence, type, severity, and frequency of TEAEs
Incidence of Serious Adverse Events (SAEs)
Time frame: 5 years (multiple visits)
Incidence, type, severity, and frequency of SAEs
Incidence of clinical laboratory abnormalities
Time frame: 5 years (multiple visits)
Incidence, type, severity, and frequency of clinical laboratory abnormalities
Incidence of new nerve conduction study (NCS) abnormalities
Time frame: 5 years (multiple visits)
Incidence, type, severity, and frequency of new nerve conduction study (NCS) abnormalities
Incidence of new physical and neurologic exam abnormalities
Time frame: 5 years (multiple visits)
Incidence, type, severity, and frequency of new physical and neurologic exam abnormalities
6 secondary outcomes
Change in Hamburg Scale, Motor and Language domain scores
Time frame: 5 years (multiple visits)
Change in Spectral Domain-Optical Coherence Tomography (SD-OCT)
Time frame: 5 years (multiple visits)
Change in Unified Batten Diseases Rating Scale (UBDRS)
Time frame: 5 years (multiple visits)
Change in Caregiver global impression of change
Time frame: 5 years (multiple visits)
Change in visual acuity measurements
Time frame: 5 years (multiple visits)
Change in color vision
Time frame: 5 years (multiple visits)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2024.
- Derived from this study: PubMed 37942487Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Gray SJ, Palmer DN, Mitchell NL. Efficacy of dual intracerebroventricular and intravitreal CLN5 gene therapy in sheep prompts the first clinical trial to treat CLN5 Batten disease. Front Pharmacol. 2023 Oct 24;14:1212235. doi: 10.3389/fphar.2023.1212235. eCollection 2023.
- Derived from this study: PubMed 37614821Mitchell NL, Murray SJ, Wellby MP, Barrell GK, Russell KN, Deane AR, Wynyard JR, Palmer MJ, Pulickan A, Prendergast PM, Casy W, Gray SJ, Palmer DN. Long-term safety and dose escalation of intracerebroventricular CLN5 gene therapy in sheep supports clinical translation for CLN5 Batten disease. Front Genet. 2023 Aug 8;14:1212228. doi: 10.3389/fgene.2023.1212228. eCollection 2023.
- Individual participant dataSharing planned: No
Related trials for Neuronal Ceroid Lipofuscinosis CLN5
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RecruitingObservational study
Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database
Neuronal Ceroid Lipofuscinosis, Batten Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Effie Albanis, MD study director
Neurogene Inc.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NGN-101 in people with Neuronal Ceroid Lipofuscinosis CLN5, run by Neurogene Inc. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment Emergent Adverse Events (TEAEs) (time frame: 5 years (multiple visits)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05228145, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2024.