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Homology Medicines has discontinued development of this program.
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HMI-203 Low Dose Level Cohort 1 | Experimental |
| |
| HMI-203 Intermediate Dose Level Cohort 2 | Experimental |
| |
| HMI-203 High Dose Level Cohort 3 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genetic HMI-203 | Biological | HMI-203 delivered intravenously |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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;
| 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;
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | week 52 to week 260 |
| Evaluate the long-term effect of HMI-203 single administration on urinary GAG levels within each dose cohort |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital Oakland | Oakland | California | 94609 | United States | ||
| Yale Center for Clinical Investigation |
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| ID | Term |
|---|---|
| D016532 | Mucopolysaccharidosis II |
| D013398 | Sudden Infant Death |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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Single urine sample GAG levels |
| week 52 to week 260 |
| 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. | Baseline through week 260 |
| Changes from baseline in 6-minute Walk Test (6MWT) performance | Change from baseline in mean 6-minute walk test (6MWT) | Baseline to timepoints between Week 52 to Week 260 |
| Changes from baseline in cardiac mass | Cardiac mass will be evaluated by performing a transthoracic 2-dimensional echocardiogram. | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline in cardiac function | Cardiac function will be evaluated by performing a transthoracic 2-dimensional echocardiogram with doppler flow. | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1 (Forced Expired Volume). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FVC (Forced Vital Capacity). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry with lung volumes for TLC (Total Lung Capacity). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry with lung volumes for RV (Residual Volume). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry with lung volumes for TV (Tidal Volume all in L). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1/FVC ratio (Forced Expiry Volume in 1 second/Forced Vital Capacity). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Changes from baseline pulmonary function by evaluating spirometry by DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide mL/min/mmHg). | Baseline; weeks 52, 104, 156, 208, and 260 |
| Change in CSF levels of heparan sulfate | Measure CSF heparan sulfate | Baseline; weeks 52, 260 |
| Change in CSF levels of dermatan sulfate | Measure CSF dermatan sulfate | Baseline; weeks 52, 260 |
| Change in CSF levels I2S activity and concentration | Measure CSF I2S activity and concentration | Baseline; weeks 52, 260 |
| Determine immune response to the HMI-203 delivery capsid by evaluating the incidence of antibodies | Measurement of anti-AAVHSC antibodies (total and neutralizing) | Baseline; weeks 52 and 260 |
| Determine immune response to iduronate 2-sulfatase enzyme (I2S) | Measurement of anti-I2S antibodies (total and neutralizing) | Baseline; weeks -1, 1, 4, 8, 12, 24, 52, 78, 104, and 260 |
| Determine immune response via cytotoxic T-lymphocyte CD8+ (ELISpot) | Baseline; week 52 |
| New Haven |
| Connecticut |
| 06519 |
| United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| University of Utah Pediatric Genetic & Metabolism Clinic | Salt Lake City | Utah | 84113 | United States |
| Lysosomal and Rare Disorders Research and Treatment Center, Inc. | Fairfax | Virginia | 22030 | United States |
| M.A.G.I.C. Clinic, Ltd. | Calgary | Alberta | T2E 7Z4 | Canada |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003645 | Death, Sudden |
| D003643 | Death |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D066088 | Infant Death |