Safety and Efficacy of HMI-203 in ERT-Treated Adults With MPS II

NCT05238324 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: HMI-203-101
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 6

Brief Summary

Phase 1, open-label, sequential ascending dose-escalation study. Designed to evaluate the safety and efficacy of a single IV infusion of investigational gene therapy HMI-203. Males, ages 18 to 45 years inclusive, with MPS II (Hunter syndrome) currently receiving idursulfase ERT (or the equivalent) are eligible to participate. Participants will be followed for safety and efficacy for 5 years.

Conditions

Mucopolysaccharidosis II

Keywords

MPS II; Hunter syndrome

Outcome Measures

Primary Outcomes (4)

• Evaluate the incidence and severity of treatment emergent adverse events (TEAEs) after a single dose administration of HMI-203 (at each dose level) in adult participants with MPS II

  The following events are defined as TEAEs; 1. Elevation in serum transaminases (concentration that is \> 1.5× ULN) and/or 2. Elevation in serum direct bilirubin (concentration that is \> 1.5× ULN)

  Baseline through 260 weeks

• Evaluate the incidence and severity of adverse events of special interest (AESIs) after a single dose administration of HMI-203 (at each dose level) in adult participants with MPS II

  The following events are defined as AESIs; 1. Elevation in serum transaminases (concentration that is \> 1.5× ULN) and/or 2. Elevation in serum direct bilirubin (concentration that is \> 1.5× ULN)

  Baseline through 260 weeks

• Evaluate the effect of HMI-203 single administration on urinary GAG levels within each dose cohort

  Single urine sample GAG levels

  Baseline to week 52

• Evaluate the effect of HMI-203 single administration on plasma I2S activity within each dose cohort

  Measure trough I2S plasma activity

  Baseline to week 52

Secondary Outcomes (19)

• Evaluate the long-term effect of HMI-203 single administration on plasma I2S activity and concentration within each dose cohort

  week 52 to week 260

• Evaluate the long-term effect of HMI-203 single administration on urinary GAG levels within each dose cohort

  week 52 to week 260

• Evaluate the effect of HMI-203 on use of ERT

  Baseline through week 260

• Changes from baseline in 6-minute Walk Test (6MWT) performance

  Baseline to timepoints between Week 52 to Week 260

• Changes from baseline in cardiac mass

  Baseline; weeks 52, 104, 156, 208, and 260

Study Arms (3)

HMI-203 Low Dose Level Cohort 1

EXPERIMENTAL

Biological: Genetic HMI-203

HMI-203 Intermediate Dose Level Cohort 2

EXPERIMENTAL

Biological: Genetic HMI-203

HMI-203 High Dose Level Cohort 3

EXPERIMENTAL

Biological: Genetic HMI-203

Interventions

Genetic HMI-203 BIOLOGICAL

HMI-203 delivered intravenously

HMI-203 High Dose Level Cohort 3; HMI-203 Intermediate Dose Level Cohort 2; HMI-203 Low Dose Level Cohort 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult males 18-45 years of age at the time of informed consent
• Has capacity and is able to understand the purpose and risks of the study and is willing, able and committed to comply with all study procedures for the duration of the trial (a total of 5 years after gene therapy administration)
• Diagnosis of MPS II based on historically decreased I2S enzyme activity and elevated urine GAGs and/or presence of hemizygous IDS pathogenic variant
• Kaufman Brief Intelligence Test-Second Edition (KBIT2) score ≥ 80
• Compliance with regular treatments of ERT for MPS II for at least 12 months prior to enrollment
• Clinically stable relative to urinary GAG levels, ambulation, and cardiopulmonary status for 12 months preceding enrollment

You may not qualify if:

• Multiple sulfatase disorder as determined by abnormal activity of another lysosomal sulfatase
• Unresponsive and/or intolerant to idursulfase treatment
• History of BMT, stem cell transplant, or gene therapy
• Presence of anti-capsid neutralizing antibodies
• ALT or AST \> ULN; Total or Direct bilirubin \> ULN
• International normalized ratio (INR) \>1.2 ULN
• Hematology values below the normal range
• Hemoglobin A1c ≥ 6.5% or fasting glucose ≥126 mg/dL
• Contraindication to corticosteroid or tacrolimus use
• Any condition that would not allow the potential participant to complete follow-up examinations during the course of the study or, in the opinion of the investigator, makes the potential participant unsuitable for the study

Sponsors & Collaborators

• Homology Medicines, Inc: lead

Study Sites (6)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Utah Pediatric Genetic & Metabolism Clinic

Salt Lake City, Utah, 84113, United States

Location

Lysosomal and Rare Disorders Research and Treatment Center, Inc.

Fairfax, Virginia, 22030, United States

Location

M.A.G.I.C. Clinic, Ltd.

Calgary, Alberta, T2E 7Z4, Canada

Location

MeSH Terms

Conditions

Mucopolysaccharidosis II; Sudden Infant Death

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant Death

Study Design

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

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: February 14, 2022
• Study Start: September 8, 2022
• Primary Completion: October 1, 2024
• Study Completion (Estimated): January 1, 2029
• Last Updated: August 28, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (5)