What side effects are associated with this type of intervention?

The most common treatments for MPS-IH (Hurler Syndrome) include gene therapy and allogeneic hematopoietic stem cell transplantation (HSCT). Gene therapy can cause immune reactions, insertional mutagenesis, and off-target effects. Allogeneic HSCT carries risks of graft-versus-host disease (GVHD), infections, and organ toxicity from the conditioning regimen.

What prior FDA approvals exist?

The FDA has approved enzyme replacement therapy (ERT) with laronidase (Aldurazyme) for the treatment of MPS-IH (Hurler Syndrome). This treatment helps to replace the deficient enzyme in patients. While gene therapy specifically for MPS-IH has not been widely approved yet, ongoing clinical trials like OTL-203 are investigating the efficacy and safety of gene therapy approaches, which aim to introduce or alter genetic material to treat or prevent the disease.

What other types of research exist?

Promising novel alternatives to OTL-203 for MPS-IH (Hurler Syndrome) patients include gene editing techniques such as CRISPR-Cas9, which is being investigated for its potential to correct genetic mutations at the DNA level. Additionally, RNA silencing therapies, which have shown efficacy in other genetic disorders by reducing the production of harmful proteins, could be considered. These approaches are still under investigation but represent cutting-edge advancements in genetic disease treatment.

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Stem Cell Transplant

Gene Therapy vs Stem Cell Treatment for Hurler Syndrome (HURCULES Trial)

Phase 3

Recruiting

Research Sponsored by Orchard Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Confirmed laboratory diagnosis of MPS-IH as demonstrated by biallelic mutation(s) in the gene coding for IDUA enzyme

Be younger than 18 years old

Must not have

Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)

Malignant neoplasia (except local skin cancer)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years post-treatment

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares a new gene therapy called OTL-203 with traditional stem cell transplants in patients with a severe genetic disorder called MPS-IH. The goal is to see if gene therapy can better correct the genetic defect causing the disease compared to replacing damaged cells with healthy ones from a donor.

Who is the study for?

This trial is for patients with Hurler syndrome (MPS-IH) who have a cognitive score of ≥70 and confirmed MPS-IH diagnosis. They must not have uncontrolled seizures, active infections resistant to treatment, severe organ damage, or other conditions that risk safety or data quality. Those previously treated with stem cell transplants or gene therapy, enrolled in another interventional study, unable to follow the protocol, or positive for certain infectious diseases are excluded.

What is being tested?

The trial compares OTL-203 (a new gene therapy) against the standard allogeneic hematopoietic stem cell transplant (HSCT). It's designed to see which one is more effective and safer for treating Hurler syndrome. Patients will be randomly assigned to receive either the experimental gene therapy or the standard HSCT treatment.

What are the potential side effects?

Potential side effects may include immune system reactions due to genetic modification in OTL-203 and complications related to stem cell transplantation like graft-versus-host disease. Specific side effects depend on individual patient responses and can vary widely.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with MPS-IH through genetic testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with MDS or AML.

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I have cancer, but it's not just skin cancer.

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I have a history of seizures that are not controlled by medication.

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I have had a bone marrow transplant or gene therapy before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Event-free survival

Secondary study objectives

Change from baseline to Year 2 in the ratio to the upper limit of normal (ULN) of urinary heparan sulfate levels

Change from baseline to Year 2 in α-L-iduronidase (IDUA) activity in leukocytes

Immune response against IDUA enzyme

+3 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: OTL-203Experimental Treatment1 Intervention

Eligible subjects randomized to Arm 1 will receive an intravenous (IV) infusion of OTL-203 gene therapy. Subjects will receive conditioning regimen with busulfan and fludarabine prior to OTL-203 infusion.

Group II: Allo-HSCTActive Control1 Intervention

Eligible subjects randomized to Arm 2 will receive allogeneic hematopoietic stem cell transplantation. Subjects will receive conditioning regimen with busulfan and fludarabine prior to allo-HSCT.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for MPS-IH (Hurler Syndrome) include gene therapy and hematopoietic stem cell transplantation (HSCT). Gene therapy works by introducing or altering genetic material within a patient's cells to correct the genetic defect, leading to the production of the missing or defective enzyme needed to break down glycosaminoglycans (GAGs). HSCT involves transplanting healthy donor stem cells that can produce the necessary enzyme to reduce GAG accumulation. Both treatments aim to restore enzyme activity, which is essential for preventing the progressive organ and tissue damage characteristic of MPS-IH.

Trends in haematopoietic cell transplantation for inborn errors of metabolism.