Gene Therapy for Batten Disease

(CLN5-200 Trial)

Not currently recruiting at 1 trial location

Overseen By Contact Center

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Neurogene Inc.

Must not be taking: Prohibited medications

Disqualifiers: Other neurologic disease, Seizure mutation, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment, NGN-101, for children with Batten Disease, specifically Subtype 5 (CLN5). The goal is to assess the treatment's safety and effectiveness at different doses. The study includes three groups receiving varying doses to find the best balance between safety and benefit. Children aged 3 to 9 years with movement, language, or vision difficulties due to this condition may be suitable for the trial. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the opportunity to be among the first to potentially benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial mentions the use of prohibited medications, but it does not specify which ones. It's best to discuss your current medications with the study team to see if any need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that NGN-101, a gene therapy for Batten disease, is still under study to assess its safety. Gene therapies like NGN-101 use a virus to deliver healthy genes to cells. Studies of similar treatments have generally found these therapies to be safe for people.

In earlier research, patients who received similar gene therapies experienced few serious side effects. The most common issues were mild, such as headaches or fevers, which usually resolved on their own. The studies on NGN-101 are among the first in humans, so researchers continue to gather information.

The trial tests different doses to evaluate their safety, with careful monitoring for any side effects. Since this trial is in an early stage, safety remains a primary focus, and close monitoring helps ensure participants' well-being. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NGN-101 for Batten Disease because it uses gene therapy with a unique approach. Unlike traditional treatments that manage symptoms, NGN-101 delivers a codon-optimized human CLN5 transgene using a recombinant serotype 9 adeno-associated virus. This gene therapy aims to correct the underlying genetic defect responsible for Batten Disease. The treatment is administered in different doses, with some cohorts receiving higher doses, potentially offering more effective results. This innovative approach could significantly alter the disease's progression, offering new hope for patients and their families.

What evidence suggests that this gene therapy could be an effective treatment for Batten disease?

Research shows that NGN-101, a gene therapy, is designed to help children with CLN5 Batten disease by providing a healthy version of the CLN5 gene to the body. This treatment aims to slow brain cell damage and prevent vision loss, common issues in this disease. Studies on similar gene therapies have shown promise in slowing neurodegenerative diseases by improving cell function. The treatment uses a virus to deliver the gene, a method safely used in other genetic conditions. While specific data for NGN-101 is still being collected, early results suggest this method could improve outcomes for children with this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Effie Albanis, MD

Principal Investigator

Neurogene Inc.

Are You a Good Fit for This Trial?

This trial is for children aged 3 to 9 with a confirmed genetic diagnosis of CLN5 Batten Disease who can walk (with or without help) and comply with study procedures like MRI scans. They must not have been in another drug study recently, have certain infections or allergies, need major surgery soon, or be on ventilatory support.

Inclusion Criteria

I can walk, even if I need some help or use a device.

I can undergo tests like blood tests, MRI, and others that may need sedation.

My condition is due to a CLN5 gene mutation.

Exclusion Criteria

I've had seizures lasting over 5 minutes or multiple seizures within 5 minutes without fully recovering in the last 12 weeks.

You have a high level of antibodies against AAV9 in your blood.

I have a genetic mutation linked to seizures, not including CLN5.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single administration of gene therapy via intracerebroventricular and intravitreal injection

1 day

Follow-up

Participants are monitored for safety and efficacy, including assessments of motor, language, visual, and cognitive function

5 years

Multiple visits

What Are the Treatments Tested in This Trial?

Interventions

• NGN-101

Trial Overview The trial tests NGN-101 gene therapy in a single dose escalation format. It's an open-label study where all participants receive the treatment. The aim is to see how different doses are tolerated and how effective they are against CLN5 Batten Disease symptoms.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon- optimized human CLN5 transgene (hCLN5opt).

Group II: Cohort 2 Experimental Treatment 1 Intervention

The study treatment is a higher dose of recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).

Group III: Cohort 1 Experimental Treatment 1 Intervention

The study treatment is a recombinant serotype 9 adeno-associated virus encoding a codon-optimized human CLN5 transgene (hCLN5opt).

Who Is Running the Clinical Trial?

Neurogene Inc.

Lead Sponsor

Trials

6

Recruited

150+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05228145

Gene Therapy Study for Children With CLN5 Batten 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

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10628725/

Efficacy of dual intracerebroventricular and intravitreal CLN5 ... This study evaluated dual intracerebroventricular (ICV) and intravitreal (IVT) administration of a self-complementary adeno-associated viral ...

3. clinicaltrial.be clinicaltrial.be/en/details/33189?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Gene Therapy Study for Children With CLN5 Batten ... The study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an ...

4. neurogene.com neurogene.com/patients-and-families/about-batten-disease/cln5-batten-disease-clinical-trial/

CLN5 Batten Disease Clinical Trial This CLN5 Batten disease gene therapy clinical trial is designed to address the neurodegeneration and vision loss associated with the disease.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8056991/

Slowing Late Infantile Batten Disease by Direct Brain ... They injected an adeno-associated virus vector expressing the normal human CLN2 coding sequence directly into the brain parenchyma of children with the disease.

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05228145/

Trial | NCT05228145 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 ...

7. frontiersin.org frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1212228/full

Long-term safety and dose escalation of ... This study evaluated the efficacy of intracerebroventricular (ICV) delivery of an adeno-associated viral vector encoding ovine CLN5 (scAAV9/oCLN5)