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Ongoing Clinical Trials for Mucopolysaccharidosis

There are currently 12 clinical trials underway across Europe studying various treatments for mucopolysaccharidosis (MPS), a group of rare genetic disorders affecting the body’s ability to break down certain complex sugars. These trials are evaluating gene therapies, enzyme replacement therapies, and novel medications aimed at improving outcomes for patients with different MPS types, including Hunter syndrome (MPS II), Hurler syndrome (MPS IH), and Sanfilippo syndrome (MPS IIIA).

Clinical trial locations

Long-term Safety and Efficacy Study of JR-141 (Pabinafusp Alfa) for Male Patients with Hunter Syndrome (Mucopolysaccharidosis II)

This trial is studying the long-term safety and effectiveness of JR-141 in male patients with Hunter syndrome, also known as MPS II. Hunter syndrome is a rare genetic disorder that prevents the body from properly breaking down complex sugars, leading to their buildup in various tissues and causing multiple health problems.

Main inclusion criteria: To participate, patients must have completed a previous study called JR-141-GS31 without safety concerns. Written consent must be provided by the patient or their legal representative. Participants or their partners who can have children must agree to use highly effective birth control throughout the study. Those with hearing problems should use hearing aids during cognitive testing.

Main exclusion criteria: Patients cannot participate if they have a condition other than Hunter syndrome, are outside the specified age range, cannot follow study procedures, have medical conditions that might interfere with the study, are taking medications that could affect results, recently participated in another trial, are pregnant or breastfeeding, or have a history of allergic reactions to the study medication.

Focus and goal: The study evaluates how well patients tolerate JR-141 over an extended period and monitors its effects on central nervous system symptoms. Participants receive the medication through intravenous injection and undergo regular assessments including liver and spleen measurements, shoulder movement tests, walking ability evaluations, and various health indicators. The trial also monitors cerebrospinal fluid concentrations, neuropsychological function, and quality of life.

Investigational drug: JR-141 (pabinafusp alfa) is a modified enzyme replacement therapy delivered intravenously. It works by providing a modified enzyme that can cross the blood-brain barrier to replace the deficient enzyme in patients, potentially improving both neurological and physical symptoms.

Long-term safety study of rebisufligene etisparvovec gene therapy in patients previously treated for Mucopolysaccharidosis type IIIA

This study focuses on the long-term effects of a gene therapy called rebisufligene etisparvovec (also known as ABO-102 or UX111) in patients with MPS IIIA, also known as Sanfilippo syndrome type A. This condition causes harmful substances to build up in the brain and nervous system, leading to progressive neurological problems.

Main inclusion criteria: Participants must have previously received UX111 in an earlier clinical trial, be between 2 and 11 years old, and have a confirmed diagnosis of MPS IIIA. Parents or legal guardians must provide written consent and be able to follow all study procedures and attend scheduled visits.

Main exclusion criteria: Patients cannot participate if they have had a stem cell transplant, joined another clinical trial within 30 days, have serious medical conditions that could interfere with the study, have known allergies to the medication, are unable to comply with procedures, are pregnant or breastfeeding, are taking prohibited medications, have planned major surgery, show significant abnormal test results, or have mental conditions affecting consent or compliance.

Focus and goal: The trial monitors long-term safety and tracks any side effects following the gene therapy treatment. Researchers evaluate cognitive development, communication abilities, levels of heparan sulfate in spinal fluid, brain volume changes, and overall survival. The study continues until August 2027 with regular medical check-ups.

Investigational drug: Rebisufligene etisparvovec uses a modified virus (AAV9) to deliver a working copy of the SGSH gene to cells, enabling the body to produce the missing enzyme needed to break down complex sugars.

Study of Weekly Infusions of JR-441 for Patients with Mucopolysaccharidosis Type IIIA

This trial evaluates JR-441 in patients with MPS IIIA, a rare genetic disorder affecting the breakdown of certain sugar molecules. The condition leads to progressive neurological deterioration as harmful substances accumulate in the brain.

Main inclusion criteria: Participants must be between 1 and 18 years old with a confirmed diagnosis of MPS IIIA, including low activity of the SGSH enzyme and specific genetic mutations. They must weigh at least 10 kg and be in stable health. Those needing hearing aids should use them consistently, especially during developmental assessments. Participants or their partners who can have children must agree to use reliable birth control.

Main exclusion criteria: The specific exclusion criteria are not detailed, but generally patients unable to follow study requirements or with conditions interfering with participation would be excluded.

Focus and goal: The study assesses the safety of weekly JR-441 infusions and explores effectiveness in managing MPS IIIA symptoms. Participants receive the medication intravenously and undergo regular monitoring for side effects, changes in blood tests, vital signs, and heart function. The trial also evaluates cognitive function and adaptive behavior. The study runs until 2030.

Investigational drug: JR-441 is a lyophilized powder prepared for intravenous injection. It uses a protein targeting specific receptors to help improve the condition, representing a form of enzyme replacement therapy.

Study on Long-Term Safety and Effects of DNL310 for Patients with Mucopolysaccharidosis Type II (MPS II)

This trial examines the long-term safety and tolerability of DNL310 in patients with MPS II. The condition causes harmful substances to accumulate in body tissues due to a missing enzyme, leading to progressive damage affecting multiple organ systems.

Main inclusion criteria: Patients must have completed at least 49 weeks in Study DNLI-E-0002 or 96 weeks in Cohort A/48 weeks in Cohort B of Study DNLI-E-0007 without stopping treatment early. Both males and females can participate, and the study includes vulnerable populations.

Main exclusion criteria: Patients with medical conditions other than MPS II, those outside the specified age range, individuals unable to follow study procedures, those with health issues interfering with the study, current participants in other trials, pregnant or breastfeeding individuals, those with allergic reactions to the medication, and people with drug or alcohol abuse history cannot participate.

Focus and goal: The study monitors safety and tolerability over up to 5 years, tracking adverse events and infusion-related reactions. Researchers measure changes in urine glycosaminoglycan concentrations, cerebrospinal fluid heparan sulfate levels, cognitive scores, walking distance, and liver and spleen volumes through regular MRI assessments.

Investigational drug: DNL310 is an intravenous enzyme replacement therapy designed to cross the blood-brain barrier, potentially addressing both neurological and physical symptoms by delivering a modified enzyme to replace the deficient one in patients.

Study on Long-Term Safety of Idursulfase-IT and Elaprase for Patients with Hunter Syndrome and Cognitive Impairment

This trial studies the long-term safety of combining two treatments for Hunter syndrome patients with cognitive impairment: idursulfase-IT (HGT-2310) delivered directly into spinal fluid and Elaprase given intravenously.

Main inclusion criteria: Only male patients who completed studies HGT-HIT-046 or SHP609-302 and benefited from idursulfase-IT can participate. Informed consent must be signed by the patient or their legal representative. Patients must have continued receiving Elaprase regularly in the previous studies.

Main exclusion criteria: Females are excluded, as are those without Hunter syndrome with cognitive impairment, patients not receiving the specific treatments being studied, and those outside the specified age range.

Focus and goal: The study monitors long-term safety by tracking adverse events related to the medication, administration device, and procedures. Participants receive idursulfase-IT through intrathecal injection using a special implantable access port, along with continued intravenous Elaprase. The trial runs until January 2034.

Investigational drugs: Idursulfase-IT is delivered directly into the spinal fluid to help manage neurological symptoms. Elaprase is an enzyme replacement therapy given intravenously to provide the missing enzyme throughout the body.

Study on the Effectiveness and Safety of DNL310 vs Idursulfase for Children and Young Adults with Mucopolysaccharidosis Type II

This comparative trial evaluates whether DNL310 offers advantages over the existing treatment idursulfase in children and young adults with MPS II. The study examines effects on both brain function and physical health.

Main inclusion criteria: Participants must be aged 2 to less than 6 years for Cohort A or 6 to less than 26 years for Cohort B, with confirmed MPS II diagnosis. Those in non-run-in cohorts must have tolerated at least 4 months of idursulfase therapy before screening.

Main exclusion criteria: Patients with conditions other than MPS II, those outside the age range, individuals unable to follow procedures, or those considered part of excluded vulnerable populations cannot participate.

Focus and goal: The study compares DNL310’s effects to idursulfase on central nervous system symptoms and overall health over 96 weeks. Researchers measure changes in cerebrospinal fluid substances, improvements in daily activities, and various health indicators. Both treatments are given as intravenous infusions.

Investigational drugs: DNL310 is an experimental enzyme replacement therapy targeting central nervous system symptoms by crossing the blood-brain barrier. Idursulfase is the approved standard enzyme replacement therapy for MPS II, helping break down accumulated substances throughout the body.

Study on the Safety and Effectiveness of Rebisufligene Etisparvovec for Patients with Mucopolysaccharidosis Type IIIA

This trial tests UX111 (ABO-102), a gene therapy for MPS IIIA, which causes progressive neurological decline due to the buildup of harmful substances in the brain and nervous system.

Main inclusion criteria: Patients must have confirmed MPS IIIA with reduced SGSH enzyme activity and specific genetic mutations. Age criteria vary by cohort, with some accepting patients from birth to 2 years and others including older children with certain cognitive development levels. For specific cohorts, vaccination status must be up to date.

Main exclusion criteria: Patients with serious medical conditions interfering with the study, recent infections, medications conflicting with treatment, recent participation in other trials, allergies to similar treatments, inability to comply with procedures, or conditions making participation unsafe are excluded.

Focus and goal: The study evaluates safety and effectiveness by monitoring adverse events and measuring changes in cerebrospinal fluid components, including heparan sulfate and gangliosides. Researchers assess cognitive and communication development using standardized scales. The trial runs until July 2027.

Investigational drug: UX111 (ABO-102) is a gene therapy using a viral vector to deliver a healthy copy of the SGSH gene, enabling cells to produce the missing enzyme and potentially slowing disease progression.

Study on Gene Therapy with Autologous Stem Cells and Drug Combination for Children with Mucopolysaccharidosis Type I Hurler Variant

This trial tests OTL-203, a gene therapy using patients’ own genetically modified blood stem cells to treat MPS I Hurler variant. This condition causes harmful substances to accumulate throughout the body due to a missing enzyme.

Main inclusion criteria: Children between 28 days and 11 years old with confirmed MPS IH diagnosis can participate. They must have a Lansky Index score above 80%, need a stem cell transplant, lack a suitable sibling or specific cord blood donor, and have healthy heart, kidney, liver, and lung function. Parents or legal guardians must provide written permission.

Main exclusion criteria: Patients with conditions other than MPS I Hurler, those outside the age range, individuals who haven’t undergone required conditioning treatment, those unable to receive the specific cell treatment, and people unable to follow procedures are excluded.

Focus and goal: The study evaluates long-term safety and effectiveness of gene therapy using modified stem cells. The process involves collecting the patient’s stem cells, genetically modifying them in a laboratory to include the IDUA gene, then infusing them back after conditioning treatment. Regular monitoring tracks engraftment, enzyme activity levels, and any complications.

Investigational drugs: The treatment uses autologous stem cells modified with the IDUA lentiviral vector, along with supporting medications including Lenograstim, Plerixafor, Busulfan, Fludarabine, and Rituximab to prepare the body and support cell engraftment.

Study on the Effectiveness and Safety of OTL-203 for Patients with Hurler Syndrome (MPS-IH) Compared to Standard Treatment with Stem Cell Transplantation

This comparative trial evaluates whether OTL-203 gene therapy provides better outcomes than standard stem cell transplantation for MPS I Hurler syndrome.

Main inclusion criteria: Children aged 28 days to 30 months (with possible exceptions for older children meeting all requirements) can participate if they have a cognitive standard score of 70 or higher and confirmed MPS-IH diagnosis. This includes specific gene mutations and low IDUA enzyme activity, confirmed by a special review committee. Parents or legal guardians must provide written consent.

Main exclusion criteria: Patients with conditions other than MPS I Hurler, those outside the age range, individuals unable to follow procedures, those with interfering medical conditions, pregnant or breastfeeding individuals, recent participants in other trials, those with specific treatment histories affecting results, people with allergies to study medication, those with substance abuse history, and individuals with certain genetic family histories are excluded.

Focus and goal: The study compares OTL-203 gene therapy to standard allogeneic stem cell transplantation, monitoring survival without major health events, enzyme activity changes, cognitive function, joint movement, and quality of life. Assessments track immune responses, infections, and complications from both treatments.

Investigational drugs: OTL-203 uses genetically modified stem cells to deliver a working copy of the deficient gene. Supporting medications include Laronidase, Plerixafor, Busulfan, Fludarabine, and Rituximab administered through various routes.

Study on the Effects and Safety of JR-141 and Idursulfase for Patients with Hunter Syndrome

This trial compares JR-141 with Elaprase (idursulfase) and placebo to evaluate effectiveness and safety in managing Hunter syndrome symptoms affecting both the brain and body.

Main inclusion criteria: Patients must voluntarily provide informed consent (or through a legal representative for minors or those with intellectual disability). Diagnosis must be confirmed by low IDS enzyme activity (10% or less of normal), documented IDS gene changes, and increased urinary substances or characteristic symptoms. Patients can be treatment-naive or on stable enzyme replacement therapy with idursulfase for over 12 weeks. Specific cognitive scores are required for different age groups in Cohort A (30-71 months) and Cohort B (6 years and older). Those with hearing loss should consistently use hearing aids.

Main exclusion criteria: Patients with conditions other than MPS II, those outside specified age ranges, individuals not part of designated trial groups, and those from excluded vulnerable populations cannot participate.

Focus and goal: The two-year study evaluates how JR-141 affects central nervous system and physical symptoms compared to standard treatment. Regular assessments include cognitive tests, liver and spleen size measurements, walking tests, and lung function evaluations. The trial monitors safety and tracks disease progression.

Investigational drug: JR-141 is an intravenous enzyme replacement therapy designed to cross the blood-brain barrier, potentially addressing both neurological and physical symptoms more effectively than current treatments.

Study on the Safety and Initial Effects of AAV9-CAG-coh-SGSH in Children with Sanfilippo A Syndrome

This trial tests AAV9-hSGSH, a gene therapy delivered directly into the brain for children with Sanfilippo A syndrome (MPS IIIA), which causes severe neurological deterioration.

Main inclusion criteria: Children aged 2 years or older with confirmed MPS IIIA (including genetic mutations and low sulfamidase enzyme activity) can participate. First symptoms must have appeared before age 6. Children should have certain adaptive behavior levels, be able to walk without wheelchair assistance, lack severe vision or hearing problems, have stable symptom treatment for 3 months, have no medical reasons preventing surgery or anesthesia, and be in stable condition for study requirements including travel.

Main exclusion criteria: Patients with conditions other than MPS IIIA, those outside the age range, individuals unable to safely receive treatment, those with interfering medical conditions, people unable to follow procedures, recent trial participants, pregnant or breastfeeding individuals, and those with known allergies to treatment components are excluded.

Focus and goal: The study evaluates safety and initial effectiveness of gene therapy delivered through intracerebroventricular injection. Monitoring includes physical exams, blood tests, MRI scans, immune response assessments, sulfamidase enzyme measurements, and evaluations of development and quality of life. The trial concludes in November 2025.

Investigational drug: AAV9-hSGSH uses an adeno-associated virus vector to deliver the human sulfamidase gene directly to the brain, aiming to restore enzyme production in affected areas.

Summary

The 12 ongoing clinical trials for mucopolysaccharidosis represent a diverse research effort across Europe, with significant concentration in countries like Spain, France, Germany, and Italy. Several trials are multi-national, reflecting the rarity of these conditions and the need for broader patient recruitment.

A notable trend is the focus on Hunter syndrome (MPS II), with multiple trials testing DNL310 and JR-141 as potential alternatives or improvements to current enzyme replacement therapy. Several studies specifically target central nervous system symptoms, which have historically been difficult to treat due to the challenge of delivering therapies across the blood-brain barrier.

Gene therapy approaches are prominently featured, particularly for MPS IIIA (Sanfilippo syndrome) and MPS I Hurler variant. These include both systemic gene therapies using viral vectors and approaches using genetically modified stem cells. The trials for MPS IIIA reflect the urgent need for effective treatments for this devastating condition, which currently lacks approved therapies.

Many trials are long-term safety studies following earlier efficacy trials, indicating that some experimental treatments have shown promising initial results and are now being evaluated for sustained safety and benefit. The age ranges across trials vary considerably, from infants to young adults, reflecting the different manifestations and progression patterns of various MPS types.

Ongoing Clinical Trials on Mucopolysaccharidosis

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