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

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

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

Study Overview

• Status: Recruiting
• Conditions: Mucopolysaccharidosis IH/S; Mucopolysaccharidosis IS
• Intervention / Treatment: Biological: Autologous Plasmablasts (B cells)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 11
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jake Wesley, PharmD, MS; Email: jake.wesley@immusoft.com

Study Locations

• United States
  • California
    • Oakland, California, United States, 94609
      • Recruiting
      • UCSF Benioff Children's Hospital Oakland
      • Contact: Matt Thura; Email: matt.thura@ucsf.edu
      • Principal Investigator: Paul Harmatz, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Principal Investigator: Paul Orchard, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous Plasmablasts (B cells) - Cohort - Target Dose A; Dose Level: 5 x 10e7 cells/kg on Day 0	Biological: Autologous Plasmablasts (B cells); Autologous plasmablasts (B cells) engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty (SB) transposon system.
Experimental: Autologous Plasmablasts (B cells) - Cohort - Target Dose B; Dose Level: Between 1 x 10e8 or to 2 x 10e8 cells/kg on Day 0	Biological: Autologous Plasmablasts (B cells); Autologous plasmablasts (B cells) engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty (SB) transposon system.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Immusoft of CA, Inc.
• Investigators: Study Director: Immusoft Clinical Development, Immusoft of CA, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2044

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 12, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: MPS IH/S; MPS IS
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Mucopolysaccharidosis I
• Other Study ID Numbers: MT2021-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No