A first-in-human study using ISP-001 in patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie.

This is a Phase 1, first-in-human, open-label, single-arm study in which 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.

Inclusion Criteria:

• Diagnosis of Mucopolysaccharidosis type I Hurler-Scheie or Scheie syndrome.
• Age ≥ 10 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.