MT2018-18: Sleeping Beauty Transposon-Engineered Plasmablasts for Hurler Syndrome Post Allo HSCT

NCT04284254 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2018LS094MT2018-18
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single center, Phase 1/2 study in which patients with Hurler syndrome who have previously undergone allogeneic hematopoietic stem cell transplantation are treated with autologous plasmablasts engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty transposon system.

Conditions

Mucopolysaccharidosis Type IH (MPS IH, Hurler Syndrome); Mucopolysaccharidosis Type IH; MPS IH, Hurler Syndrome

Keywords

MPS IH; Hurler syndrome

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  Maximum tolerated dose (MTD) of autologous plasmablasts engineered to express large amounts of α-L-iduronidase (IDUA) using a Sleeping Beauty transposon approach

  1 Year

• Growth Velocity (cm/year)

  Growth velocity in centimeters/year over a one-year period through determinations of sitting and standing height at baseline and post infusion

  1 Year

• Safety and Tolerability after Infusion: Incidence of Adverse Events

  Incidence of Adverse Events

  1 Year

Secondary Outcomes (3)

• Z-score Growth Rate

  1 Year

• Donor Engraftment

  Baseline, 6 months and 1 Year

• Levels of circulating antibodies (IgG, IgM, IgA and IgE)

  1 Year

Study Arms (2)

Phase 1: Dose Escalation

EXPERIMENTAL

Drug: Autologous Plasmablasts

Phase 2 - Expansion at MTD

EXPERIMENTAL

Drug: Autologous Plasmablasts

Interventions

Autologous Plasmablasts DRUG

Autologous Plasmablasts engineered to express α-L-iduronidase (IDUA) using the Sleeping Beauty transposon system. Phase 1: * Dose Level 1: 5 x 10e7 cells/kg on Day 0 * Dose Level 2: 1 x 10e8 cells/kg on Day 0 * Dose Level 3: 1 x 10e8 cells/kg x 2 doses on Day 0 and Day 30 +/-3 days. Phase 2: \- Maximum Tolerated Dose (MTD) established in Phase I

Also known as: Sleeping Beauty

Phase 1: Dose Escalation; Phase 2 - Expansion at MTD

Eligibility Criteria

• Age: 3 Years - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of Mucopolysaccharidosis type IH (MPS IH, Hurler syndrome)
• Underwent a previous hematopoietic stem cell transplant \>1 year prior to study enrollment
• Age ≥3 years and ≤8 years at time of study registration
• ≥ 10 kilograms body weight
• Creatinine \<1.5 normal for gender and age.
• Ejection fraction ≥ 40% by echocardiogram
• Must commit to traveling to the University of Minnesota for the necessary followup evaluations
• Must agree to stay in the Twin Cities area (\<45-minute drive from the Masonic Children's Hospital) for a minimum of 5 days after each cell infusion
• Voluntary written parental consent prior to the performance of any study related procedures

You may not qualify if:

• Prior enzyme replacement therapy within 4 months prior to enrolling on study
• History of B cell related cancer, EBV lymphoproliferative disease or autoimmune disorders
• Evidence of active graft vs. host disease
• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

MeSH Terms

Conditions

Mucopolysaccharidosis I

Interventions

sleeping beauty transposase, human

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Paul Orchard, MD

  University of Minnesota, Department of Pediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: February 25, 2020
• Study Start: December 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: October 7, 2022

Record last verified: 2022-10