JR-171 for Hurler Syndrome

No longer recruiting at 6 trial locations

Overseen By JCR Pharmaceuticals Co., Ltd.

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: JCR Pharmaceuticals Co., Ltd.

Must be taking: Laronidase

Disqualifiers: Gene therapy, Pregnancy, Serious drug allergy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a new treatment called JR-171 (lepunafusp alfa) for individuals with Mucopolysaccharidosis I (MPS I), a rare genetic disorder that impairs the body's ability to break down certain sugars. Researchers will evaluate how the body processes the drug and whether it improves symptoms. Participants will receive the treatment through an intravenous (IV) infusion, with doses adjusted to determine the optimal amount. The trial is open to those diagnosed with MPS I who have been taking another treatment, laronidase, for at least three months. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants must have been on a stable dosage of laronidase for at least 2 weeks before starting the trial, unless they are laronidase naïve or have had a specific treatment called HSCT.

Is there any evidence suggesting that JR-171 (lepunafusp alfa) is likely to be safe for humans?

Research has shown that JR-171, also known as lepunafusp alfa, has been tested for safety in treating mucopolysaccharidosis type I (MPS I). A 52-week study found that JR-171 is generally safe for long-term use in people with this condition. The results revealed no major safety issues, suggesting that the treatment is likely well-tolerated. In these studies, patients received JR-171 through an IV drip, and researchers tested different doses to ensure safety at various levels. While more research is needed, these early results are promising for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Mucopolysaccharidosis I (MPS I) focus on enzyme replacement therapy, such as laronidase, to help break down the complex sugars that build up in the body. However, JR-171 (lepunafusp alfa) offers something new by crossing the blood-brain barrier, potentially addressing neurological symptoms that other treatments cannot reach. Researchers are excited about JR-171 because it not only involves a unique delivery method—an IV infusion with dose escalation—but it also holds promise for more comprehensive symptom management by targeting the brain directly, which is a significant step forward in treating MPS I.

What evidence suggests that JR-171 might be an effective treatment for MPS I?

Research shows that JR-171, also known as lepunafusp alfa, could help treat mucopolysaccharidosis type I (MPS I). Studies suggest this treatment might improve both physical and brain-related symptoms of MPS I. JR-171 is a specially designed protein that combines an enzyme with an antibody to better target cells. Early findings indicate it may improve conditions in patients with nerve-related MPS I over a 52-week period. These initial results are promising for those considering joining this trial, which includes different treatment arms with varying doses of JR-171. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Inclusion Criteria

Activity of IDUA enzyme below 10% of lower reference level in leucocytes or cultured skin fibroblasts, AND increased age-related urinary levels of GAGs (before enzyme replacement therapy)

Activity of IDUA enzyme below 10% of lower reference level in leucocytes or cultured skin fibroblasts, AND presence of one pathogenic mutation in each of the alleles of the IDUA gene

Increased age-related urinary levels of GAGs (before enzyme replacement therapy), AND presence of one pathogenic mutation in each of the alleles of the IDUA gene

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive JR-171 intravenously with dose escalation, either 2.0 or 4.0 mg/kg/week

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• JR-171 (lepunafusp alfa)

How Is the Trial Designed?

Group I: Part2 JR-171 Experimental Treatment 1 Intervention

Drug: JR-171 IV infusion, dose escalation, low dose, high dose

Group II: Part1 JR-171 Experimental Treatment 1 Intervention

Drug: JR-171 IV infusion, dose escalation

Who Is Running the Clinical Trial?

JCR Pharmaceuticals Co., Ltd.

Lead Sponsor

Trials

13

Recruited

320+

Published Research Related to This Trial

In a study of 10 patients with juvenile dermatomyositis (JDM) treated with Janus kinase inhibitors (JAKis) for at least 6 months, 5 patients achieved clinically inactive disease, indicating that JAKis can be effective for refractory cases.

While JAKis showed promise in improving muscle vasculopathy and reducing steroid use, there was a notable risk of herpes zoster infections in some patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. Le Voyer, T., Gitiaux, C., Authier, FJ., et al.[2021]

In a study of 101 patients with juvenile dermatomyositis (JDM), Janus kinase inhibitors (JAKi) showed promising results, with 65.5% of patients experiencing improved rashes and 39.6% able to eliminate glucocorticoids after a median follow-up of 19 months.

Cytokine analysis revealed that certain cytokines, particularly IL-1RA, were significantly elevated in active JDM patients, and a panel of six cytokines was developed to effectively differentiate between active and stable disease states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis. Huang, B., Wang, X., Niu, Y., et al.[2023]

The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommends that oral Janus kinase inhibitors (JAKi) should only be used in patients aged 65 and older or those with cardiovascular disease risk factors when no suitable alternatives are available, highlighting safety concerns.

Despite these precautions, the benefit-risk profile of JAKi remains favorable for patients with atopic dermatitis under 65 years old and without cardiovascular or malignancy risk factors, allowing for their use as first-line systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed look at the European Medicines Agency's recommendations for use of Janus kinase inhibitors in patients with atopic dermatitis. Wollenberg, A., Thyssen, JP., Bieber, T., et al.[2023]

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S1525001624000091

Original Article α-L-iduronidase fused with humanized anti ...

We have developed a novel genetically modified protein consisting of IDUA fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa; JR- ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04453085

NCT04453085 | An Extension Study of JR-171-101 ...

Drug : JR-171. Intravenous (IV) infusion. Other Names: lepunafusp alfa. What is the study measuring? Primary Outcome Measures. Outcome Measure, Measure ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10220318/

Enzyme replacement with transferrin receptor-targeted α-L ...

This study provides nonclinical evidence that JR-171 might potentially prevent and even improve disease conditions in patients with neuronopathic MPS I without ...

4.

biospace.com

biospace.com/jcr-pharmaceuticals-announces-52-week-interim-data-from-its-global-phase-i-ii-study-of-jr-171-in-individuals-with-mucopolysaccharidosis-type-i-mps-i

JCR Pharmaceuticals Announces 52-Week Interim Data ...

“Based on these data, JR-171 has the potential to treat both the somatic and neurological symptoms of individuals with MPS I, which is ...

5.

cell.com

cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(24)00009-1

α-L-iduronidase fused with humanized anti ...

This article presents the results of the first-in-human study of JR-171 in patients with MPS I, in which the safety, tolerability, and ...

6.

researchgate.net

researchgate.net/publication/377889087_Efficacy_and_safety_data_52-week_from_a_phase_12_trial_and_extension_study_of_JR-171_lepunafusp_alfa_used_in_enzyme_replacement_therapy_for_patients_with_MPS_I

Efficacy and safety data (52-week) from a phase 1/2 trial ...

Efficacy and safety data (52-week) from a phase 1/2 trial and extension study of JR-171 (lepunafusp alfa) used in enzyme replacement therapy ...