Mucopolysaccharidosis Type IPhase 1NCT06519552
A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of JWK008 in Patients With Mucopolysaccharidosis Type I
A Phase 1 study testing JWK008 Single intravenous infusion administration in people with Mucopolysaccharidosis Type I, run by West China Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucopolysaccharidosis Type I
- What is being tested?
- JWK008 Single intravenous infusion administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 22 Jul 2024to 22 Jun 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 19Show fewer
- 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.
- Previously received gene therapy or participated in interventional clinical studies within the past 12 weeks;
- Pregnant or lactating females.
- The researcher believes that the subject is not suitable to participate in any concurrent clinically significant major diseases or other situations in the study;
- Unable or unwilling to comply with the visit and study evaluation schedule described in the clinical protocol.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
West China Hospital, Sichuan Universit
Chengdu, Sichuan, 610041
XingChen Peng, Ph.D, +8618980606753, pxx2014@163.com
About this study
Official title: 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 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.
Read the detailed description
MPS I is a rare autosomal recessive disease caused by deficiency of the α-L-iduronidase (IDUA) gene, which encodes a lysosomal enzyme required for degradation of glycosaminoglycans (GAGs).While currently available therapies, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), provide clinical benefit over untreated disease progression,they still have significant limitations. ERT does not cross the blood-brain barrier and, therefore, does not treat the central nervous system (CNS) effects of the disease. And HSCT, although it can prevent cognitive decline in patients, has a high mortality rate and morbidity. The investigators have designed a novel IDUA fusion protein with the ability to cross the blood-brain barrier through the addition of the brain-targeting peptide Mtfp. On this basis, the investigators constructed an IDUA gene expression cassette for liver-targeted expression, and used a highly efficient liver-specific promoter to make the IDUA gene specifically and efficiently expressed in liver tissue, and the expressed protein can enter the central nervous system to exert therapeutic effects.
- Conditions
- Mucopolysaccharidosis Type I
- Being tested
- JWK008 Single intravenous infusion administration
- Keywords
- Mucopolysaccharidosis Type I, MPS I, Gene Therapy, AAV, Adeno-associated virus
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JWK008 Single intravenous infusion administrationGenetic
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.
| Study group | Role | What they receive |
|---|---|---|
| JWK008 injection | Experimental | The participants will be given 5.0×10^12vg/kg or 2.0×10^13vg/kg body weight of JWK008 Receives: Genetic: JWK008 Single intravenous infusion administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
adverse events
Adverse events defined as the number of participants with adverse events according CTCAE 5.0
Measured: 5 years
Secondary outcomes (6)
IDUA enzyme activity in blood and cerebrospinal fluid
Changes in IDUA activity in blood and cerebrospinal fluid before and after treatment are detected by laboratory testing.
Measured: 5 years
GAG levels in blood, urine, and cerebrospinal fluid
Changes in GAG levels in blood, urine, and cerebrospinal fluid before and after treatment are detected by laboratory testing.
Measured: 5 years
Six-Minute Walk Test
The distance that the patient could withstand the fastest walking distance on flat ground within 6 minutes before and after treatment was measured
Measured: 5 years
Range of the joint motion(JROM) testing by measuring ruler
A measuring ruler was used to detect changes in the participant's range of the joint motion before and after treatment
Measured: 5 years
Liver and spleen size were detected by CT
Changes in liver and spleen size were detected by CT
Measured: 5 years
Vector shedding
As measured by vector concentration (quantitative polymerase chain reaction to JWK008 deoxyribonucleic acid ) in CSF, serum, and urine
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2024
- Study start22 Jul 2024 (estimated)
- Primary completion22 Jun 2026 (estimated)
- Study completion22 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mucopolysaccharidosis Type IStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xingchen Peng, West China Hospital
- Investigators
- Xingchen Peng, Ph.D, Principal investigator, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06519552
- Sponsor's protocol ID
- 2023-1287
- Status last verified
- Jul 2024
- First submitted
- 23 Jun 2024
- Last updated
- 25 Jul 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study Evaluating the Safety, Tolerability, and Initial Efficacy of JWK008 Given by a Single Intravenous Infusion in Patients With Mucopolysaccharidosis Type I
- ClinicalTrials.gov ID
- NCT06519552
- Acronym / sponsor ID
- 2023-1287
- Conditions
- Mucopolysaccharidosis Type I
- Keywords
- Mucopolysaccharidosis Type I, MPS I, Gene Therapy, AAV, Adeno-associated virus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 22 Jul 2024 (estimated)
- Primary completion
- 22 Jun 2026 (estimated)
- Study completion
- 22 Jun 2029 (estimated)
- First posted
- 25 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
MPS I is a rare autosomal recessive disease caused by deficiency of the α-L-iduronidase (IDUA) gene, which encodes a lysosomal enzyme required for degradation of glycosaminoglycans (GAGs).While currently available therapies, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), provide clinical benefit over untreated disease progression,they still have significant limitations. ERT does not cross the blood-brain barrier and, therefore, does not treat the central nervous system (CNS) effects of the disease. And HSCT, although it can prevent cognitive decline in patients, has a high mortality rate and morbidity. The investigators have designed a novel IDUA fusion protein with the ability to cross the blood-brain barrier through the addition of the brain-targeting peptide Mtfp. On this basis, the investigators constructed an IDUA gene expression cassette for liver-targeted expression, and used a highly efficient liver-specific promoter to make the IDUA gene specifically and efficiently expressed in liver tissue, and the expressed protein can enter the central nervous system to exert therapeutic effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| JWK008 injection | Experimental | Genetic: JWK008 Single intravenous infusion administrationThe participants will be given 5.0×10^12vg/kg or 2.0×10^13vg/kg body weight of JWK008 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JWK008 Single intravenous infusion administrationSix 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. | Genetic | JWK008 injection |
Primary outcome
adverse events
Time frame: 5 years
Adverse events defined as the number of participants with adverse events according CTCAE 5.0
6 secondary outcomes
IDUA enzyme activity in blood and cerebrospinal fluid
Time frame: 5 years
GAG levels in blood, urine, and cerebrospinal fluid
Time frame: 5 years
Six-Minute Walk Test
Time frame: 5 years
Range of the joint motion(JROM) testing by measuring ruler
Time frame: 5 years
Liver and spleen size were detected by CT
Time frame: 5 years
Vector shedding
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Individual participant dataSharing planned: No
Related trials for Mucopolysaccharidosis Type I
RecruitingObservational study
Cardiac Structure and Function in MPS
MPS I, MPS IV A
Not yet recruitingPhase 3
A Study to Investigate the Safety, Pharmacokinetics (PK), and Efficacy of Garetosmab in Children and Adolescents With Fibrodysplasia Ossificans Progressiva (FOP)
Fibrodysplasia Ossificans Progressiva, FOP
Active, not recruitingPhase 1/2
An Open-label Phase I/II Study of JR-446 in Mucopolysaccharidosis Type IIIB
Mucopolysaccharidosis III-B
RecruitingPhase 1/2
A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)
Mucopolysaccharidosis IIIB
Active, not recruitingPhase 1/2
Phase I/II Study of JR-441 in Patients With Mucopolysaccharidosis Type IIIA
Mucopolysaccharidosis III-A
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Xingchen Peng, Ph.D principal investigator
West China Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JWK008 Single intravenous infusion administration in people with Mucopolysaccharidosis Type I, run by West China Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xingchen Peng, Ph.D (+8618980606753, pxx2014@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
adverse events (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.