N-Acetyl-L-Leucine for Niemann-Pick Disease Type C

Recruiting at 16 trial locations

Overseen By Michael Strupp, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: IntraBio Inc

Must not be taking: N-Acetyl-DL-Leucine, Sulfasalazine

Disqualifiers: Hypersensitivity, Pregnancy, Severe vision impairment, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called N-acetyl-L-leucine for individuals with Niemann-Pick Disease Type C (NPC), a rare genetic disorder that impairs the body's ability to process cholesterol and other fats. The researchers aim to determine if this treatment is safe and effective compared to the usual care for NPC. Participants will be randomly assigned to receive either the new treatment or a placebo (a substance with no therapeutic effect) to compare outcomes. Individuals with a confirmed diagnosis of NPC who can manage daily life activities and are willing to share their current treatment plans might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, like N-Acetyl-DL-Leucine, N-Acetyl-L-Leucine (unless provided in the trial), Sulfasalazine, and Rosuvastatin, for at least 42 days before starting the study and throughout its duration. However, you can continue other medications for Niemann-Pick Disease Type C if they have been stable for at least 42 days before the trial and remain unchanged during the study.

Is there any evidence suggesting that N-acetyl-L-leucine is likely to be safe for humans?

Research has shown that N-acetyl-L-leucine (IB1001) is safe for treating Niemann-Pick disease type C. In one study, patients who took this treatment for 12 weeks showed better brain function than those who took a placebo, indicating good tolerance of the treatment.

An international trial also reported positive safety results for IB1001. Although specific side effects were not listed, the positive outcomes suggest that serious side effects were rare. The trial phase indicates that earlier stages have already tested the treatment, supporting its safety.

Overall, while more long-term information may be needed, current evidence suggests that N-acetyl-L-leucine is generally safe for people with Niemann-Pick disease type C. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Niemann-Pick disease type C?

N-Acetyl-L-Leucine is unique because it offers a novel approach to treating Niemann-Pick Disease Type C by potentially stabilizing or improving neurological symptoms more effectively than existing treatments. Unlike standard therapies that primarily manage symptoms or slow disease progression, this compound acts on the central nervous system with a new mechanism of action. Researchers are excited about N-Acetyl-L-Leucine as it could provide better symptom control and an improved quality of life for patients, especially since it's administered orally and tailored to age-specific dosages.

What evidence suggests that N-Acetyl-L-Leucine might be an effective treatment for Niemann-Pick Disease Type C?

Research has shown that N-acetyl-L-leucine (IB1001), which participants in this trial may receive, may help treat Niemann-Pick Disease Type C (NPC). Studies have found that this modified amino acid greatly improves symptoms like movement and thinking abilities compared to a placebo. It also appears to protect the brain, potentially slowing the disease's progression. Those who have used N-acetyl-L-leucine previously have experienced significant benefits, suggesting it could be a helpful treatment for individuals with NPC. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals aged 4 and older with a confirmed genetic diagnosis of Niemann-Pick disease type C. Participants must weigh at least 15 kg, have stable medication doses, and not be pregnant or breastfeeding. Men must agree to use contraception, and women who can bear children must either abstain from sex or use effective birth control.

Inclusion Criteria

I am 4 years or older and have a confirmed genetic diagnosis of NPC.

Written informed consent signed by the patient and/or their legal representative/parent/impartial witness

I agree to share my current NPC symptom treatments and keep doses consistent.

Exclusion Criteria

I have not been in a drug study within the last 42 days.

I do not have any health conditions that could risk my safety or affect the study's results.

I can avoid certain medications for 42 days before my first visit and until my sixth visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Baseline

Baseline assessments conducted before randomization

2 weeks

2 visits (in-person)

Treatment Period I

Participants receive either IB1001 or Placebo for 12 weeks

12 weeks

2 visits (in-person)

Treatment Period II

Participants crossover to receive the opposite treatment for 12 weeks

12 weeks

2 visits (in-person)

Extension Phase

Participants may opt into continuation of treatment with IB1001

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• N-Acetyl-L-Leucine

Trial Overview The study tests the safety and effectiveness of N-Acetyl-L-Leucine (IB1001) compared to a placebo in treating Niemann-Pick disease type C. It's randomized, meaning participants are randomly assigned to receive either the drug or placebo without choosing which one.

How Is the Trial Designed?

Group I: N-acetyl-L-leucine (IB1001) Experimental Treatment 1 Intervention

Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day); patients \<13 will receive weight-tiered doses.

Group II: Placebo comparator Placebo Group 1 Intervention

Oral administration (granule in a sachet for suspension in water, orange juice, or almond milk). Patients ≥13 years old will receive a total daily dose of 4 g/day (administered as 3 doses per day); patients \<13 will receive weight-tiered doses.

Who Is Running the Clinical Trial?

IntraBio Inc

Lead Sponsor

Trials

5

Recruited

220+

Published Research Related to This Trial

The innovative master protocol and primary outcome assessment for N-acetyl-L-leucine (IB1001) are designed to address the unique challenges of treating ultra-rare neurodegenerative disorders, involving three multinational phase II trials for Niemann-Pick disease type C, GM2 gangliosidoses, and ataxia telangiectasia.

The novel Clinical Impression of Change in Severity (CI-CS) assessment allows for a personalized evaluation of treatment effects, capturing meaningful clinical changes in patients' functional performance, which is crucial for understanding the efficacy of N-acetyl-L-leucine in these rare diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A master protocol to investigate a novel therapy acetyl-L-leucine for three ultra-rare neurodegenerative diseases: Niemann-Pick type C, the GM2 gangliosidoses, and ataxia telangiectasia. Fields, T., Patterson, M., Bremova-Ertl, T., et al.[2021]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL-.0000000000205236

Results of a Phase III, Randomized, Placebo-controlled ... NALL demonstrated a statistically significant improvement over placebo with a clinically meaningful benefit in symptoms (motor and cognitive), functioning, ...

2. nnpdf.org nnpdf.org/wp-content/uploads/2024/02/IntraBio-Bremova-Ertl-NEJM-Publication-02.01.2024.pdf

Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C We evaluated the safety and efficacy of N-acetyl-l-leucine (NALL) ... Long-term survival outcomes of patients with Niemann–Pick disease type.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37248494/

N-acetyl-L-leucine for Niemann-Pick type C: a multinational ... The modified amino acid N-acetyl-leucine has been associated with positive symptomatic and neuroprotective, disease-modifying effects in various studies.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03759639

N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC) The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the symptomatic treatment of NPC. The Extension Phase evaluates the long- ...

5. intrabio.com intrabio.com/news/intrabio-reports-positive-data-from-ib1001-multinational-clinical-trial-for-the-treatment-of-niemann-pick-disease-type-c/

IntraBio Reports Positive Data from IB1001 Multinational ... IntraBio Inc today announced positive data from its multinational clinical trial of IB1001 for the treatment of Niemann-Pick disease Type C (NPC).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38294974/

Trial of N-Acetyl-l-Leucine in Niemann-Pick Disease Type C Among patients with Niemann-Pick disease type C, treatment with NALL for 12 weeks led to better neurologic status than placebo.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03759639

N-Acetyl-L-Leucine for Niemann-Pick Disease, Type C (NPC) The Parent Study evaluates the safety and efficacy of N-Acetyl-L-Leucine (IB1001) for the symptomatic treatment of NPC. The Extension Phase evaluates the long- ...