Miglustat for Batten Disease

Overseen By Mary Beth Kiser

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Beyond Batten Disease Foundation

Must not be taking: Flupirtine, Brineura

Disqualifiers: Medical condition, Abnormal lab values, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of an oral medication called miglustat for individuals with CLN3 disease, a genetic condition affecting the nervous system. Researchers aim to determine how well patients tolerate different doses of miglustat and whether it can help manage symptoms over two years. The trial is open to individuals aged 17 and older with a confirmed genetic diagnosis of CLN3 disease. Participants must attend regular clinic visits and follow the study plan. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you do not use any therapy intended to modify the course of neuronal ceroid lipofuscinosis disease, such as flupirtine or cerliponase alfa. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that miglustat is likely to be safe for humans?

Research has shown that miglustat has been safe in past studies. These studies found that patients generally tolerated the treatment well, and it helped slow physical decline compared to past data. Some side effects occurred, but they were usually mild and manageable. The FDA has already approved miglustat for other conditions, which increases confidence in its safety for humans. Overall, the evidence suggests that miglustat is safe for treating conditions like Batten disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Miglustat is unique because it offers a new approach to treating Batten Disease by targeting the underlying mechanisms of the condition. Most current treatments for Batten Disease focus on managing symptoms rather than addressing the root cause. Miglustat works by inhibiting glycosphingolipid synthesis, which may help slow disease progression. Researchers are excited about miglustat because this new mechanism of action could potentially offer improved outcomes for patients with Batten Disease.

What evidence suggests that miglustat might be an effective treatment for Batten disease?

Research has shown that miglustat might help with Batten disease. In previous studies, patients took miglustat and were checked every six months. The main focus was on how quickly their condition changed using a special Batten disease scale. Results showed that miglustat could slow down the worsening of symptoms. This suggests that miglustat might be effective for treating Batten disease. Participants in this trial will receive oral miglustat to further evaluate its effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Gary D. Clark, MD

Principal Investigator

Texas Children Hospital

An N. Dang Do, MD, PhD

Principal Investigator

National Institute of Health Clinical Center

Are You a Good Fit for This Trial?

This trial is for individuals aged 17 or older with genetically confirmed CLN3 disease, a form of Batten Disease. Participants must be able to perform study tasks and visit the clinic as needed. They should agree to use effective contraception during the trial and for a month after it ends.

Inclusion Criteria

Individuals have provided informed consents (TCH and NIH) by subject or parent/legal guardian/legally authorized representative (as appropriate).

Individuals have provided informed consents (TCH and NIH) by subject or parent/legal guardian/legally authorized representative (as appropriate)

I am using or willing to use effective birth control during and for 30 days after the trial.

Exclusion Criteria

Individuals have a medical condition that in the opinion of the PI would interfere with the safety assessments or increase the subject's risk of AEs

I have not used treatments like flupirtine or Brineura for neuronal ceroid lipofuscinosis.

Have, in the opinion of the PI, a clinically significant abnormality in their clinical laboratory values (hematology, chemistry, or urinalysis) at screening that would preclude their participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral miglustat at the maximum tolerable dose for CLN3 disease

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Miglustat

Trial Overview The study tests Miglustat's safety, how it's processed in the body (pharmacokinetics), and effectiveness in treating CLN3 disease at doses from 100 mg once daily up to 200 mg three times daily over two years across two centers.

How Is the Trial Designed?

Group I: Oral miglustat Experimental Treatment 1 Intervention

The proposed dosing regimen is daily oral miglustat (MTD, up to 200 mg TID)

Miglustat is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zavesca for:

• Type I Gaucher disease
• Niemann-Pick disease type C
• Pompe disease (in combination with cipaglucosidase alfa)

Approved in United States as Zavesca for:

• Type I Gaucher disease

Approved in Canada as Zavesca for:

• Type I Gaucher disease
• Niemann-Pick disease type C

Approved in Japan as Zavesca for:

• Type I Gaucher disease
• Niemann-Pick disease type C

Who Is Running the Clinical Trial?

Beyond Batten Disease Foundation

Lead Sponsor

Trials

2

Recruited

20,000+

Theranexus

Industry Sponsor

Trials

5

Recruited

310+

Published Research Related to This Trial

Miglustat, an oral medication developed for type 1 Gaucher disease, works by inhibiting glucosylceramide glucosyltransferase, which is crucial for managing this genetic disorder.

Approved in the EU in November 2002 and launched in the UK in March 2003, miglustat is also being explored for treating other glycolipid storage disorders, indicating its potential broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Miglustat. Oxford GlycoSciences/Actelion. Lachmann, RH.[2016]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL.0000000000214110

Long-Term Open-Label Study Evaluating Oral Miglustat ... Patients were assessed every 6 months using the Unified Batten Disease Rating Scale (UBDRS). The primary outcome was the annual rate of change ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05174039

Study Details | NCT05174039 | An Open-label Safety, ... This is an open label study in approximately 6 subjects in 2 centers to assess the safety, PK, and efficacy of the maximum tolerable dose (MTD) of oral ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7736171/

an expert update on agents in preclinical and clinical trials The Neuronal Ceroid Lipofuscinoses (NCLs; Batten disease) are a group of rare inherited fatal diseases that are characterized by the buildup of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05174039?cond=%22Ceroid%20Lipofuscinosis,%20Neuronal,%203%22&intr=%22hypoglycemic%20agents%22&viewType=Table&rank=1

An Open-label Safety, Pharmacokinetic, and Efficacy Study ... This is an open label study in approximately 6 subjects in 2 centers to assess the safety, PK, and efficacy of the maximum tolerable dose (MTD) of oral ...

5. firstwordpharma.com firstwordpharma.com/story/6060801

Long-Term Open-Label Study Evaluating Oral Miglustat ... Patients were assessed every 6 months using the Unified Batten Disease Rating Scale (UBDRS). The primary outcome was the annual rate of change ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12424071/

Long-Term Open-Label Study Evaluating Oral Miglustat ... Miglustat showed a favorable safety profile and was associated with a slower rate of physical decline compared with historical controls.

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000214224

Is Miglustat an Effective Treatment for CLN3 (Batten) ... Long-term open-label study evaluating oral miglustat treatment in patients with neuronal ceroid lipofuscinosis ... Quantifying physical decline in juvenile ...

8. journals.sagepub.com journals.sagepub.com/doi/10.1177/08830738251374538

Visual Recovery and Neurological Stabilization Following ... An open-label safety study of batten-1 (miglustat) for the treatment of CLN3 disease: preliminary safety and pharmacokinetic (PK) results. Paper ...