Mucopolysaccharidosis I
Conditions
Interventions
Single group:JWK008 Single intravenous infusion administration
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Subjects who meet all the following criteria are eligible for enrollment: (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
Exclusion criteria: Those who meet any of the following criteria are not eligible for enrollment: (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: a. 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); b. Hepatitis C virus antibody (HCV-Ab) is positive, and the copy number of hepatitis C virus ribonucleic acid (HCV-RNA) is>ULN; c. Receiving antiviral treatment for hepatitis B or C; d. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| IDUA enzyme activity;GAG levels in blood, urine, and cerebrospinal fluid;Six-Minute Walk Test;Range of the joint motion;Upper limb muscle strength test;Pulmonary function tests;Liver and spleen size;Vector shedding; | — |
Countries
China
Contacts
Public ContactXingchen Peng
West China Hospital, Sichuan University
Outcome results
None listed