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

Phase 1
Recruiting
Conditions
Mucopolysaccharidosis IH/S
Mucopolysaccharidosis IS
Interventions
Biological: Autologous Plasmablasts (B cells)
Registration Number
NCT05682144
Lead Sponsor
Immusoft of CA, Inc.
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Autologous Plasmablasts (B cells)Autologous Plasmablasts (B cells)Dose Level: 5 x 10e7 cells/kg on Day 0
Primary Outcome Measures
NameTimeMethod
Number of participants with treatment-related adverse events and serious adverse events24 Weeks

Incidence of Adverse Events as assessed by CTCAE (v 5.0)

Secondary Outcome Measures
NameTimeMethod
Determination of Absolute Numbers of B and T cell populations1Year

Determination of Absolute Numbers of B and T cell populations in peripheral blood at baseline and at scheduled time points post infusion.

Assessment of Storage Material (glycosaminoglycan, or GAG)1 Year

Assessment of Storage Material (glycosaminoglycan, or GAG) in urine at baseline and at scheduled time points post infusion.

Number of participants with treatment-related adverse events and serious adverse events48 Weeks

Incidence of Adverse Events as assessed by CTCAE (v 5.0)

Levels of Circulating Antibodies (IgG, IgM, IgA, and IgE)1 Year

Determine levels of circulating antibodies (IgG, IgM, IgA, and IgE) at baseline and at scheduled time points post infusion.

Concentration of IDUA1 Year

Determine IDUA concentration in plasma at baseline and at scheduled time points post infusion.

Analysis of PBMCs1 Year

PBMCs will be analyzed at baseline and at scheduled time points post infusion.

Trial Locations

Locations (2)

UCSF Benioff Children's Hospital Oakland

🇺🇸

Oakland, California, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

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