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Mucopolysaccharidosis IIPhase 1NCT05238324

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

A Phase 1 study testing Genetic HMI-203 in people with Mucopolysaccharidosis II, run by Homology Medicines, Inc at 6 sites in 2 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 45 years, men only
Conditions the study is for
Mucopolysaccharidosis II
What is being tested?
Genetic HMI-203
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
6 sitesin 2 countries
Study dates
8 Sep 2022to Jan 2029
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Men only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States5 sites

  • Lysosomal and Rare Disorders Research and Treatment Center, Inc.

    Fairfax, Virginia, 22030

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Yale Center for Clinical Investigation

    New Haven, Connecticut, 06519

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • University of Utah Pediatric Genetic & Metabolism Clinic

    Salt Lake City, Utah, 84113

Other trials in United States

Canada1 site

  • M.A.G.I.C. Clinic, Ltd.

    Calgary, Alberta, T2E 7Z4

Other trials in Canada

About this study

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)

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.

Read the 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.

Being tested
Genetic HMI-203
Keywords
MPS II, Hunter syndrome
Medical subject headings
Mucopolysaccharidosis II, Sudden Infant Death

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Genetic HMI-203Biological

    HMI-203 delivered intravenously

Study groups in NCT05238324
Study groupRoleWhat they receive
HMI-203 Low Dose Level Cohort 1ExperimentalNot described
Receives: Biological: Genetic HMI-203
HMI-203 Intermediate Dose Level Cohort 2ExperimentalNot described
Receives: Biological: Genetic HMI-203
HMI-203 High Dose Level Cohort 3ExperimentalNot described
Receives: Biological: Genetic HMI-203

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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)

    Measured: Baseline through 260 weeks

  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

    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)

    Measured: Baseline through 260 weeks

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

    Single urine sample GAG levels

    Measured: Baseline to week 52

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

    Measure trough I2S plasma activity

    Measured: Baseline to week 52

Secondary outcomes (19)

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

    Measure trough I2S plasma activity and measure trough I2S plasma concentration

    Measured: week 52 to week 260

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

    Single urine sample GAG levels

    Measured: week 52 to week 260

  3. Evaluate the effect of HMI-203 on use of ERT

    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.

    Measured: Baseline through week 260

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

    Change from baseline in mean 6-minute walk test (6MWT)

    Measured: Baseline to timepoints between Week 52 to Week 260

  5. Changes from baseline in cardiac mass

    Cardiac mass will be evaluated by performing a transthoracic 2-dimensional echocardiogram.

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

  6. Changes from baseline in cardiac function

    Cardiac function will be evaluated by performing a transthoracic 2-dimensional echocardiogram with doppler flow.

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

  7. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1 (Forced Expired Volume).

    Measured: 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).

    Measured: 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).

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

  10. Changes from baseline pulmonary function by evaluating spirometry with lung volumes for RV (Residual Volume).

    Measured: 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).

    Measured: 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).

    Measured: 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).

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

  14. Change in CSF levels of heparan sulfate

    Measure CSF heparan sulfate

    Measured: Baseline; weeks 52, 260

  15. Change in CSF levels of dermatan sulfate

    Measure CSF dermatan sulfate

    Measured: Baseline; weeks 52, 260

  16. Change in CSF levels I2S activity and concentration

    Measure CSF I2S activity and concentration

    Measured: Baseline; weeks 52, 260

  17. Determine immune response to the HMI-203 delivery capsid by evaluating the incidence of antibodies

    Measurement of anti-AAVHSC antibodies (total and neutralizing)

    Measured: Baseline; weeks 52 and 260

  18. Determine immune response to iduronate 2-sulfatase enzyme (I2S)

    Measurement of anti-I2S antibodies (total and neutralizing)

    Measured: Baseline; weeks -1, 1, 4, 8, 12, 24, 52, 78, 104, and 260

  19. Determine immune response via cytotoxic T-lymphocyte CD8+ (ELISpot)

    Measured: Baseline; week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Feb 2022
  2. Study start8 Sep 2022
  3. Primary completionOct 2024 (estimated)
  4. Study completionJan 2029 (estimated)

Why it stopped: Homology Medicines has discontinued development of this program.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05238324
Sponsor's protocol ID
HMI-203-101
Status last verified
Aug 2023
First submitted
7 Dec 2021
Last updated
28 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Genetic HMI-203 in people with Mucopolysaccharidosis II, run by Homology Medicines, Inc at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05238324.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2023.

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