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Trial record 1 of 1 for:    NCT05238324
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Safety and Efficacy of HMI-203 in ERT-Treated Adults With MPS II

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ClinicalTrials.gov Identifier: NCT05238324
Recruitment Status : Withdrawn (Homology Medicines has discontinued development of this program.)
First Posted : February 14, 2022
Last Update Posted : August 28, 2023
Sponsor:
Information provided by (Responsible Party):
Homology Medicines, Inc

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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis II Biological: Genetic HMI-203 Phase 1

Detailed Description:

This Phase 1 study will evaluate the safety and efficacy of HMI-203 gene therapy in adult male participants with MPS II currently being treated with standard-of-care idursulfase ERT or equivalent. Participants will receive a single dose of HMI-203 administered intravenously. There are 3 planned dose cohorts which will consist of 3 participants each.

Entry into the first dose cohort will be separated by a 60-day dosing interval between each participant to allow the Homology Medicines medical monitor to review safety and efficacy data prior to the second and third participants being enrolled. Enrollment of subsequent participants, in cohorts 2 and 3, will be separated by a 21-day dosing interval between each participant for review of safety and efficacy data.

Escalation to the next dose cohort will occur after 21 days of safety, efficacy, and biomarker data have been reviewed by the Homology Medicines independent DMC.

This entire study is comprised of 5 years, with the most frequent follow up visits occurring in the first year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-203 in ERT-Treated Adults With Mucopolysaccharidosis Type II (MPS II) (juMPStart Trial)
Actual Study Start Date : September 8, 2022
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : January 2029


Arm Intervention/treatment
Experimental: HMI-203 Low Dose Level Cohort 1 Biological: Genetic HMI-203
HMI-203 delivered intravenously

Experimental: HMI-203 Intermediate Dose Level Cohort 2 Biological: Genetic HMI-203
HMI-203 delivered intravenously

Experimental: HMI-203 High Dose Level Cohort 3 Biological: Genetic HMI-203
HMI-203 delivered intravenously




Primary Outcome Measures :
  1. 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 [ Time Frame: Baseline through 260 weeks ]

    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)

  2. 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 [ Time Frame: Baseline through 260 weeks ]

    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)

  3. Evaluate the effect of HMI-203 single administration on urinary GAG levels within each dose cohort [ Time Frame: Baseline to week 52 ]
    Single urine sample GAG levels

  4. Evaluate the effect of HMI-203 single administration on plasma I2S activity within each dose cohort [ Time Frame: Baseline to week 52 ]
    Measure trough I2S plasma activity


Secondary Outcome Measures :
  1. Evaluate the long-term effect of HMI-203 single administration on plasma I2S activity and concentration within each dose cohort [ Time Frame: week 52 to week 260 ]
    Measure trough I2S plasma activity and measure trough I2S plasma concentration

  2. Evaluate the long-term effect of HMI-203 single administration on urinary GAG levels within each dose cohort [ Time Frame: week 52 to week 260 ]
    Single urine sample GAG levels

  3. Evaluate the effect of HMI-203 on use of ERT [ Time Frame: Baseline through week 260 ]
    Incidence of ERT discontinuation by 52 weeks following HMI-203 administration and among participants who have discontinued ERT by 52 weeks. Annualized frequency of ERT infusions at weeks 24, 52, 76, 104, 156, 208 and 260.

  4. Changes from baseline in 6-minute Walk Test (6MWT) performance [ Time Frame: Baseline to timepoints between Week 52 to Week 260 ]
    Change from baseline in mean 6-minute walk test (6MWT)

  5. Changes from baseline in cardiac mass [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
    Cardiac mass will be evaluated by performing a transthoracic 2-dimensional echocardiogram.

  6. Changes from baseline in cardiac function [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
    Cardiac function will be evaluated by performing a transthoracic 2-dimensional echocardiogram with doppler flow.

  7. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1 (Forced Expired Volume). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  8. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FVC (Forced Vital Capacity). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  9. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for TLC (Total Lung Capacity). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  10. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for RV (Residual Volume). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  11. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for TV (Tidal Volume all in L). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  12. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1/FVC ratio (Forced Expiry Volume in 1 second/Forced Vital Capacity). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  13. Changes from baseline pulmonary function by evaluating spirometry by DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide mL/min/mmHg). [ Time Frame: Baseline; weeks 52, 104, 156, 208, and 260 ]
  14. Change in CSF levels of heparan sulfate [ Time Frame: Baseline; weeks 52, 260 ]
    Measure CSF heparan sulfate

  15. Change in CSF levels of dermatan sulfate [ Time Frame: Baseline; weeks 52, 260 ]
    Measure CSF dermatan sulfate

  16. Change in CSF levels I2S activity and concentration [ Time Frame: Baseline; weeks 52, 260 ]
    Measure CSF I2S activity and concentration

  17. Determine immune response to the HMI-203 delivery capsid by evaluating the incidence of antibodies [ Time Frame: Baseline; weeks 52 and 260 ]
    Measurement of anti-AAVHSC antibodies (total and neutralizing)

  18. Determine immune response to iduronate 2-sulfatase enzyme (I2S) [ Time Frame: Baseline; weeks -1, 1, 4, 8, 12, 24, 52, 78, 104, and 260 ]
    Measurement of anti-I2S antibodies (total and neutralizing)

  19. Determine immune response via cytotoxic T-lymphocyte CD8+ (ELISpot) [ Time Frame: Baseline; week 52 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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

Key Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05238324


Locations
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United States, California
UCSF Benioff Children's Hospital Oakland
Oakland, California, United States, 94609
United States, Connecticut
Yale Center for Clinical Investigation
New Haven, Connecticut, United States, 06519
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Utah
University of Utah Pediatric Genetic & Metabolism Clinic
Salt Lake City, Utah, United States, 84113
United States, Virginia
Lysosomal and Rare Disorders Research and Treatment Center, Inc.
Fairfax, Virginia, United States, 22030
Canada, Alberta
M.A.G.I.C. Clinic, Ltd.
Calgary, Alberta, Canada, T2E 7Z4
Sponsors and Collaborators
Homology Medicines, Inc
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Responsible Party: Homology Medicines, Inc
ClinicalTrials.gov Identifier: NCT05238324    
Other Study ID Numbers: HMI-203-101
First Posted: February 14, 2022    Key Record Dates
Last Update Posted: August 28, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Homology Medicines, Inc:
MPS II
Hunter syndrome
Additional relevant MeSH terms:
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Mucopolysaccharidosis II
Mucopolysaccharidoses
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System