A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of JWK008 in Patients With Mucopolysaccharidosis Type I

NCT06519552 | Recruiting Phase 1

• 1 other identifier: 2023-1287
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, single-arm, non-randomized, open-label, non controlled, dose-escalation, prospective clinical trial designed to assess the safety, tolerability, and preliminary efficacy of JWK008 injection in patients with MPS I.

Conditions

Mucopolysaccharidosis Type I

Keywords

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

Outcome Measures

Primary Outcomes (1)

• adverse events

  Adverse events defined as the number of participants with adverse events according CTCAE 5.0

  5 years

Secondary Outcomes (6)

• IDUA enzyme activity in blood and cerebrospinal fluid

  5 years

• GAG levels in blood, urine, and cerebrospinal fluid

  5 years

• Six-Minute Walk Test

  5 years

• Range of the joint motion(JROM) testing by measuring ruler

  5 years

• Liver and spleen size were detected by CT

  5 years

Study Arms (1)

JWK008 injection

EXPERIMENTAL

The participants will be given 5.0×10\^12vg/kg or 2.0×10\^13vg/kg body weight of JWK008

Genetic: JWK008 Single intravenous infusion administration

Interventions

JWK008 Single intravenous infusion administration GENETIC

Six participants with MPS I will be enrolled in the study. The participantss will be divided into two different dose groups, and a "3+3" dose escalation design is used. The low dose is 5.0×10\^12vg/kg, and the high dose is 2.0×10\^13vg/kg. Only one intravenous infusion of JWK008 will be administered to each participant.

JWK008 injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥ 18 years old;
• Diagnosis of MPS type I;
• Be able to understand the purpose, content, and possible risks of this clinical study, voluntarily participate in and sign the informed consent form;
• 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.
• Magnetic resonance imaging (MRI) of the liver mass read by the radiologist is negative.

You may not qualify if:

• 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.
• Serum AAV5 neutralizing antibody titer is greater than 1:100.
• Has contraindications for Corticosteroids.
• Current treatment with systemic (intravenous or oral) immunomodulators or steroid use (topical treatments such as asthma or eczema are allowed).
• Has contraindications for lumbar puncture.
• When filtering, one of the following situations exists:
• 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);
• Hepatitis C virus antibody (HCV-Ab) is positive, and the copy number of hepatitis C virus ribonucleic acid (HCV-RNA) is\>ULN;
• Receiving antiviral treatment for hepatitis B or C;
• The human immunodeficiency virus (HIV) test is positive and the CD4+T lymphocyte count is ≤ 200/mm3;
• 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.).
• Have a history of chronic infections or other chronic diseases that researchers believe pose an unacceptable risk;
• 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;
• History of active malignancy within the past 5 years (non-melanotic skin cancer or carcinoma in situ of the cervix is allowed).
• Circulating alpha-fetoprotein (AFP) is elevated or abnormal.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital, Sichuan Universit

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Conditions

Mucopolysaccharidosis I

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Xingchen Peng, Ph.D

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng, Ph.D

CONTACT

+8618980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Professor

Study Record Dates

• First Submitted: June 23, 2024
• First Posted: July 25, 2024
• Study Start: July 22, 2024
• Primary Completion (Estimated): June 22, 2026
• Study Completion (Estimated): June 22, 2029
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)