Evaluating JWK008 for Mucopolysaccharidosis Type I

A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of JWK008 Given by a Single Intravenous Infusion in Patients With Mucopolysaccharidosis Type I

This study is testing a new gene therapy called JWK008 to see if it can safely help people with Mucopolysaccharidosis Type I by improving their symptoms.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06519552 on ClinicalTrials.gov

What this trial studies

This clinical trial is designed to assess the safety, tolerability, and initial efficacy of JWK008, a novel gene therapy, in patients with Mucopolysaccharidosis Type I (MPS I). The study employs a single-center, open-label, non-randomized, dose-escalation approach to evaluate the effects of a single intravenous infusion of JWK008. The therapy aims to address the limitations of current treatments by enabling the IDUA enzyme to cross the blood-brain barrier, potentially providing therapeutic benefits for both systemic and central nervous system symptoms of MPS I. Participants will be closely monitored for safety and efficacy outcomes throughout the trial.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older diagnosed with Mucopolysaccharidosis Type I who can provide informed consent.

Not a fit: Patients who have previously shown unresponsiveness to enzyme replacement therapy or have serious adverse reactions to related treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with MPS I by addressing both systemic and neurological symptoms.

How similar studies have performed: While gene therapy approaches for MPS I are emerging, this specific method utilizing an IDUA fusion protein is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Age≥ 18 years old;
2. Diagnosis of MPS type I;
3. Be able to understand the purpose, content, and possible risks of this clinical study, voluntarily participate in and sign the informed consent form;
4. If the subject is female, her sexual partner must agree to use reliable contraception until 2 consecutive tests of vector sequence in the blood are negative; If the subject is male, the subject agrees to use reliable contraception until the semen sample is negative for 2 consecutive tests of the vector sequence.
5. Magnetic resonance imaging (MRI) of the liver mass read by the radiologist is negative.

Exclusion Criteria:

1. Known to be unresponsive to ERT; or those who have been treated with intrathecal or intravenous laronidase and have serious adverse reactions, such as significant infusion-related reactions (IARs) or anaphylactic shock.
2. Serum AAV5 neutralizing antibody titer is greater than 1:100.
3. Has contraindications for Corticosteroids.
4. Current treatment with systemic (intravenous or oral) immunomodulators or steroid use (topical treatments such as asthma or eczema are allowed).
5. Has contraindications for lumbar puncture.
6. When filtering, one of the following situations exists:

   1. Hepatitis B surface antigen (HBsAg) is positive, and the copy number of hepatitis B virus deoxyribonucleic acid (HBV-DNA) is\>the upper limit of normal value (ULN);
   2. Hepatitis C virus antibody (HCV-Ab) is positive, and the copy number of hepatitis C virus ribonucleic acid (HCV-RNA) is\>ULN;
   3. Receiving antiviral treatment for hepatitis B or C;
   4. The human immunodeficiency virus (HIV) test is positive and the CD4+T lymphocyte count is ≤ 200/mm3;
7. Abnormal laboratory values considered clinically significant (ALT and/or AST \>3× upper limit of normal (ULN), total bilirubin \> 1.5× ULN, serum creatinine \> 1.5× ULN, etc.).
8. Have a history of chronic infections or other chronic diseases that researchers believe pose an unacceptable risk;
9. Active severe infection or any other significant accompanying, uncontrolled medical condition(except for those caused by MPS I), including but not limited to kidney, liver, blood, gastrointestinal, endocrine, lung, nervous system, brain or mental illness, alcoholism, drug dependence, or any psychological disorder assessed by the researcher that may interfere with adherence to experimental protocol procedures or tolerance to JWK008 injection;
10. History of active malignancy within the past 5 years (non-melanotic skin cancer or carcinoma in situ of the cervix is allowed).
11. Circulating alpha-fetoprotein (AFP) is elevated or abnormal.
12. Previously received gene therapy or participated in interventional clinical studies within the past 12 weeks;
13. Pregnant or lactating females.
14. The researcher believes that the subject is not suitable to participate in any concurrent clinically significant major diseases or other situations in the study;
15. Unable or unwilling to comply with the visit and study evaluation schedule described in the clinical protocol.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan Universit — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Xingchen Peng, Ph.D — West China Hospital
• Study coordinator: Xingchen Peng, Ph.D

Conditions Mucopolysaccharidosis Type I; MPS I; Gene Therapy; AAV; Adeno-associated virus