ISP-001: Sleeping Beauty Transposon-Engineered B Cells for MPS I

Study Overview
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Brief Summary
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A first-in-human study using ISP-001 in adult patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie.

Detailed Description
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This is a Phase 1, first-in-human, open-label, single-arm study in which adult patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie are treated with autologous plasmablasts engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty transposon system (ISP-001). This study will evaluate the safety and tolerability of ISP-001.

Official Title
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A Phase I Open Label Study to Evaluate the Safety and Tolerability of ISP-001 in Adult Patients With Mucopolysaccharidosis Type I Hurler-Scheie and Scheie

Conditions
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Mucopolysaccharidosis IH/S, Mucopolysaccharidosis IS

Intervention / Treatment
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* Biological: Autologous Plasmablasts (B cells)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Mucopolysaccharidosis type I Hurler-Scheie or Scheie syndrome. Age ≥ 18 years at time of study registration. Creatinine clearance, calculated or measured directly, that is >60ml/min/1.73m2. Ejection fraction ≥ 40% by echocardiogram. Must commit to traveling to the study site for the necessary follow-up evaluations. Must agree to stay <45-minute drive from the study site for a minimum of 5 days after cell infusion. Exclusion Criteria: Known familial inherited cancer syndrome. Suspected cases will be investigated, per the physicians discretion, using relevant genetic tests to determine presence of germline mutations. History of B cell related cancer, EBV lymphoproliferative disease or autoimmune disorders. Evidence of active graft-vs-host disease. Underwent a previous hematopoietic stem cell transplant (HSCT). Requirement for systemic immune suppression. Requirement for continuous supplemental oxygen. Any medical condition likely to interfere with assessment of safety or efficacy of the study treatment. In the investigator's judgement, the subject is unlikely to complete all protocol-required study visits or procedures, including follow up visits, or comply with the study requirements for participation. Other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous Plasmablasts (B cells)<br>Dose Level: 5 x 10e7 cells/kg on Day 0 | Biological: Autologous Plasmablasts (B cells)<br>* Autologous plasmablasts (B cells) engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty (SB) transposon system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events and serious adverse events | Incidence of Adverse Events as assessed by CTCAE (v 5.0) | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events and serious adverse events | Incidence of Adverse Events as assessed by CTCAE (v 5.0) | 48 Weeks | 
| Determination of Absolute Numbers of B and T cell populations | Determination of Absolute Numbers of B and T cell populations in peripheral blood at baseline and at scheduled time points post infusion. | 1Year | 
| Concentration of IDUA | Determine IDUA concentration in plasma at baseline and at scheduled time points post infusion. | 1 Year | 
| Assessment of Storage Material (glycosaminoglycan, or GAG) | Assessment of Storage Material (glycosaminoglycan, or GAG) in urine at baseline and at scheduled time points post infusion. | 1 Year | 
| Levels of Circulating Antibodies (IgG, IgM, IgA, and IgE) | Determine levels of circulating antibodies (IgG, IgM, IgA, and IgE) at baseline and at scheduled time points post infusion. | 1 Year | 
| Analysis of PBMCs | PBMCs will be analyzed at baseline and at scheduled time points post infusion. | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS IH/S, MPS IS