A Study of JR-171 in Patients With Mucopolysaccharidosis I

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

18 Participants Needed

Trial Summary

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.

What safety data exists for JR-171 (lepunafusp alfa) or similar treatments?

There is no specific safety data available for JR-171 (lepunafusp alfa) in the provided research articles. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new treatment for patients with mucopolysaccharidosis type I (MPS I). The goal is to see if the treatment is safe and how it behaves in the body. The treatment likely works by replacing or supplementing a missing enzyme. Laronidase, an enzyme replacement therapy, has been used to treat MPS I by supplementing the deficient alpha-L-iduronidase enzyme.

Eligibility Criteria

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

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

Treatment Details

Interventions

• JR-171 (lepunafusp alfa)

Participant Groups

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+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis. [2023]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of canakinumab in the treatment of systemic juvenile idiopathic arthritis in Japanese patients: Results from an open-label Phase III study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

JAK inhibitors and black box warnings: what is the future for JAK inhibitors? [2023]