Gene Therapy for Sanfilippo Syndrome

Recruiting at 2 trial locations

Overseen By HCPs Contact: Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ultragenyx Pharmaceutical Inc

Must not be taking: Prednisolone, Strong CYP3A4 inhibitors

Disqualifiers: HIV, Hepatitis, Cardiomyopathy, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of a gene therapy treatment called UX111 (also known as ABO-102 or scAAV9.U1a.hSGSH) for MPS IIIA, or Sanfilippo Syndrome, a rare genetic disorder affecting the breakdown of certain sugars in the body. The study tests different doses to determine the most effective one. Suitable participants include those diagnosed with MPS IIIA who exhibit noticeable symptoms or genetic findings related to this condition. The trial divides participants into groups receiving different doses, and they must not have certain other medical conditions or infections. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for those seeking new treatment options.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention avoiding certain substances like grapefruit juice and specific drugs that interact with sirolimus. It's best to discuss your current medications with the trial team to ensure safety and compliance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ABO-102, also known as scAAV9.U1a.hSGSH, has been tested in earlier studies for Sanfilippo Syndrome, a rare disease. In these studies, patients received a single dose of the treatment intravenously. Results indicated that most patients tolerated the treatment well. However, as with any medical treatment, some side effects were reported. Although specific details about these side effects were not widely shared, the treatment received special recognition from health authorities, suggesting confidence in its safety.

This trial is in Phase 2/3, indicating some existing information about the treatment's effectiveness in people. This phase usually follows earlier studies that found the treatment safe enough for larger groups. While this is promising, it is important to remember that reactions can vary. Anyone considering joining the trial should discuss the potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ABO-102 and scAAV9.U1a.hSGSH for Sanfilippo Syndrome because these gene therapies have the potential to address the root cause of the condition rather than just managing symptoms. Unlike standard treatments that focus on symptomatic relief, these therapies use a vector to deliver a healthy copy of the SGSH gene directly to the patient's cells. This approach could potentially halt or even reverse the progression of the disease by enabling the body to produce the enzyme it lacks. The possibility of a one-time treatment providing long-lasting benefits is a major leap forward compared to current management options.

What evidence suggests that this trial's treatments could be effective for Sanfilippo Syndrome?

Research has shown that ABO-102, a type of gene therapy, holds potential for treating MPS IIIA, a form of Sanfilippo Syndrome. Studies indicate that this treatment can lower harmful substances in the brain, potentially slowing the disease's progression. Early data suggest that the therapy can safely deliver a healthy version of the SGSH gene to critical areas like the central nervous system. Importantly, this gene therapy has demonstrated long-term safety, indicating it is generally well-tolerated by patients. These findings offer hope that ABO-102 could effectively treat MPS IIIA by targeting the disease's root cause.

In this trial, participants will receive varying doses of the gene therapy, from low to high, to evaluate its safety and effectiveness across different treatment arms. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Ultragenyx Pharmaceutical Inc

Are You a Good Fit for This Trial?

This trial is for children diagnosed with MPS IIIA, a genetic disorder. Eligible participants are from birth to 2 years old or older than 2 with a cognitive score of at least 60. They must have confirmed mutations in the SGSH gene and reduced enzyme activity. Children can't join if they have uncontrolled seizures, heart issues, previous gene therapy, or conditions that interfere with testing.

Inclusion Criteria

I am under 2 years old or older with a cognitive score above 60.

I have been diagnosed with MPS IIIA through specific genetic and enzyme tests.

Exclusion Criteria

I am not pregnant nor have I tested positive for pregnancy.

You have a high level of antibodies against AAV9 in your blood.

I have a condition that makes spinal taps unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous dose of UX111 (scAAV9.U1a.hSGSH) with optional prophylactic immunomodulatory therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including CSF Heparan Sulfate and Ganglioside exposure, up to 24 months

24 months

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ABO-102
• scAAV9.U1a.hSGSH

Trial Overview The study tests ABO-102's effectiveness and safety in treating MPS IIIA alongside adjuvant immunosuppression therapy. It aims to see how well this gene transfer approach works by delivering a functional copy of the SGSH gene into patients.

How Is the Trial Designed?

Group I: Cohort 4 High Dose (Spain Only) Experimental Treatment 3 Interventions

Dose of 3 X 10\^13 vg/kg

Group II: Cohort 3 High Dose Experimental Treatment 3 Interventions

Dose of 3 X 10\^13 vg/kg

Group III: Cohort 2 Mid Dose Experimental Treatment 3 Interventions

Dose of 1 X 10\^13 vg/kg

Group IV: Cohort 1 Low Dose Experimental Treatment 3 Interventions

Dose of 0.5 X 10\^13 vg/kg

Who Is Running the Clinical Trial?

Ultragenyx Pharmaceutical Inc

Lead Sponsor

Trials

94

Recruited

104,000+

Dr. Emil D. Kakkis

Ultragenyx Pharmaceutical Inc

Chief Executive Officer since 2010

MD/PhD in Biological Chemistry from UCLA

Dr. Eric Crombez

Ultragenyx Pharmaceutical Inc

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Abeona Therapeutics, Inc

Industry Sponsor

Trials

12

Recruited

1,100+

Published Research Related to This Trial

In a study involving 21 patients with Sanfilippo syndrome type A, treatment with intrathecal recombinant human heparan-N-sulfatase (rhHNS) was generally well tolerated, with mostly mild adverse events and no treatment-related deaths over a period of up to 96 weeks.

While most patients experienced cognitive decline, a small number showed improvements in specific developmental areas, suggesting that earlier intervention may enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter open-label extension study of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A. Wijburg, FA., Whitley, CB., Muenzer, J., et al.[2022]

Gene therapy for Sanfilippo A syndrome is feasible, as demonstrated by the successful use of a retroviral vector to deliver the sulfamidase gene, resulting in complete correction of the enzymatic defect in fibroblasts.

The study achieved phenotypic correction even at low levels of viral transduction, indicating that effective gene therapy may not require high viral loads, but careful selection of target cells is crucial for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction of Sanfilippo A skin fibroblasts by retroviral vector-mediated gene transfer. Bielicki, J., Hopwood, JJ., Anson, DS.[2008]

Sanfilippo disease, a type of mucopolysaccharidosis (MPS III), is caused by genetic defects leading to the accumulation of heparan sulfate, resulting in severe neurodegenerative changes and cognitive disabilities.

While there are currently no approved therapies for Sanfilippo disease, recent advancements in clinical trials are exploring enzyme replacement therapy, gene therapy, and substrate reduction therapy as potential treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How close are we to therapies for Sanfilippo disease? Gaffke, L., Pierzynowska, K., Piotrowska, E., et al.[2019]

Sanfilippo A syndrome (MPS-IIIA) is caused by a deficiency in the enzyme sulphamidase, which is essential for breaking down heparan sulphate, leading to lysosomal storage issues.

The sulphamidase gene, located on chromosome 17, consists of 8 exons and spans about 11 kilobases, with detailed analysis of its structure and sequence providing insights into the genetic basis of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structure and sequence of the human sulphamidase gene. Karageorgos, LE., Guo, XH., Blanch, L., et al.[2022]

The novel intracerebral gene therapy for Sanfilippo B demonstrated a good safety profile over 5.5 years, with no serious drug reactions reported despite 30 treatment-emergent adverse events, three of which were severe.

Sustained enzyme production was observed in the cerebrospinal fluid, and while one younger patient showed cognitive improvement, the older patients did not exhibit significant cognitive benefits, suggesting that earlier intervention may be crucial for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral Gene Therapy in Four Children with Sanfilippo B Syndrome: 5.5-Year Follow-Up Results. Deiva, K., Ausseil, J., de Bournonville, S., et al.[2022]

In a study of 19 patients with Sanfilippo syndrome type B, cognitive abilities, adaptive behavior, and brain volume declined over 12 months, particularly in younger patients diagnosed before age 6, indicating significant disease progression.

While urine GAG and cerebrospinal fluid heparan sulfate levels remained stable, younger patients had higher levels, suggesting these biomarkers may have prognostic value but need further investigation to confirm their sensitivity to disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B. Whitley, CB., Cleary, M., Eugen Mengel, K., et al.[2019]

In a phase IIb trial involving 21 patients with Sanfilippo syndrome type A, intrathecal administration of recombinant human heparan-N-sulfatase (rhHNS) successfully reduced levels of heparan sulfate and glycosaminoglycans in the cerebrospinal fluid and urine, indicating a biochemical response to treatment.

Although the primary goal of preventing neurocognitive decline was not achieved, the treatment was generally safe with mostly mild adverse events, and no serious complications or deaths occurred, suggesting that rhHNS IT may be a tolerable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. Wijburg, FA., Whitley, CB., Muenzer, J., et al.[2019]

Hematopoietic stem cell gene therapy (HSCGT) using a lentiviral vector for the SGSH gene shows promise for treating Mucopolysaccharidosis type IIIA (MPSIIIA), with pre-clinical studies indicating effective gene transfer and safety in humanized mouse models.

The therapy demonstrated effective engraftment and biodistribution without vector shedding or germline transmission, and showed low genotoxicity, suggesting it is a safe and viable option for clinical trials in treating this neurological disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical Safety and Efficacy of Lentiviral Vector-Mediated Ex Vivo Stem Cell Gene Therapy for the Treatment of Mucopolysaccharidosis IIIA. Ellison, SM., Liao, A., Wood, S., et al.[2020]

A phase 1/2 study involving four young children with Mucopolysaccharidosis type IIIB showed that intracerebral gene therapy using rAAV2/5 was well tolerated, with no unexpected serious adverse reactions, and resulted in improved neurocognitive progression compared to the natural history of the disease.

The therapy led to sustained production of the NAGLU enzyme in the brain, and the youngest patient showed cognitive function close to that of healthy children, suggesting that early intervention may be crucial for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial. Tardieu, M., Zérah, M., Gougeon, ML., et al.[2022]

Sanfilippo syndrome (MPS III) is a neurodegenerative disorder caused by enzyme deficiencies that lead to heparan sulfate accumulation, resulting in severe neurological symptoms starting in childhood, but currently, there is no effective therapy available.

Research using animal models has advanced the understanding of MPS III and is paving the way for potential treatments, including planned clinical trials for enzyme replacement and gene therapy specifically targeting MPS IIIA and MPS IIIB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sanfilippo syndrome: causes, consequences, and treatments. Fedele, AO.[2022]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL.98.18_supplement.213

Updated results of Transpher A, a multicenter, single-dose ... Investigational ABO-102 in patients with MPS IIIA showed a favorable long-term safety profile and led to significant reductions in central ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04088734

Gene Transfer Study of ABO-102 in Patients With Middle ... This is an open-label, single dose clinical trial. All participants will receive 3 X 10^13 vg/kg of ABO-102 delivered one time through a venous catheter ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02716246

Study Details | NCT02716246 | Phase I/II/III Gene Transfer ... The main objective of this study is to evaluate the efficacy and safety of UX111 for the treatment of MPS IIIA.

4. ir.ultragenyx.com ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-acquires-global-rights-aav-gene-therapy-abo-102

Ultragenyx Acquires Global Rights to AAV Gene Therapy ... ABO-102 / UX111 is being evaluated in ongoing pivotal Transpher A trial in patients with MPS IIIA. Interim data featured in encore oral ...

5. investors.abeonatherapeutics.com investors.abeonatherapeutics.com/press-releases/detail/198/new-positive-phase-12-interim-data-presented-at

New Positive Phase 1/2 Interim Data Presented at ... The data shows ABO-102's ability to deliver a functional copy of the disease-causing SGSH gene to cells of the CNS and peripheral organs, as ...

6. investors.abeonatherapeutics.com investors.abeonatherapeutics.com/press-releases/detail/56/abeona-therapeutics-announces-fast-track-designation-from

Abeona Therapeutics Announces Fast Track Designation ... Abeona Therapeutics Announces Fast Track Designation from FDA for ABO-102 in Sanfilippo Syndrome Type A. Download as PDF October 25, 2016 ...

7. ir.ultragenyx.com ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-receives-complete-response-letter-fda-ux111-aav-gene

Ultragenyx Receives Complete Response Letter from FDA ... Ultragenyx Receives Complete Response Letter from FDA for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA). July 11, 2025.

8. clinicalleader.com clinicalleader.com/doc/abeona-therapeutics-announces-data-clinical-trial-for-sanfilippo-syndrome-type-a-0001

Abeona Therapeutics Announces Data Safety Monitoring ... ABO-102 is an adeno-associated viral (AAV)-based gene therapy for patients with MPS IIIA (Sanfilippo syndrome), that is delivered as a one-time ...