Clinical trial NCT05238324: Safety and Efficacy of HMI-203 in ERT-Treated Adults With MPS II
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Mucopolysaccharidosis II
Keywords: MPS II
Hunter syndrome
Lead sponsor: Homology Medicines, Inc
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
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
timeFrame: Baseline through 260 weeks
measure: 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
timeFrame: Baseline through 260 weeks
measure: Evaluate the effect of HMI-203 single administration on urinary GAG levels within each dose cohort
timeFrame: Baseline to week 52
measure: Evaluate the effect of HMI-203 single administration on plasma I2S activity within each dose cohort
timeFrame: Baseline to week 52
Secondary outcomes:
measure: Evaluate the long-term effect of HMI-203 single administration on plasma I2S activity and concentration within each dose cohort
timeFrame: week 52 to week 260
measure: Evaluate the long-term effect of HMI-203 single administration on urinary GAG levels within each dose cohort
timeFrame: week 52 to week 260
measure: Evaluate the effect of HMI-203 on use of ERT
timeFrame: Baseline through week 260
measure: Changes from baseline in 6-minute Walk Test (6MWT) performance
timeFrame: Baseline to timepoints between Week 52 to Week 260
measure: Changes from baseline in cardiac mass
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline in cardiac function
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1 (Forced Expired Volume).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FVC (Forced Vital Capacity).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry with lung volumes for TLC (Total Lung Capacity).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry with lung volumes for RV (Residual Volume).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry with lung volumes for TV (Tidal Volume all in L).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry with lung volumes for FEV1/FVC ratio (Forced Expiry Volume in 1 second/Forced Vital Capacity).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Changes from baseline pulmonary function by evaluating spirometry by DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide mL/min/mmHg).
timeFrame: Baseline; weeks 52, 104, 156, 208, and 260
measure: Change in CSF levels of heparan sulfate
timeFrame: Baseline; weeks 52, 260
measure: Change in CSF levels of dermatan sulfate
timeFrame: Baseline; weeks 52, 260
measure: Change in CSF levels I2S activity and concentration
timeFrame: Baseline; weeks 52, 260
measure: Determine immune response to the HMI-203 delivery capsid by evaluating the incidence of antibodies
timeFrame: Baseline; weeks 52 and 260
measure: Determine immune response to iduronate 2-sulfatase enzyme (I2S)
timeFrame: Baseline; weeks -1, 1, 4, 8, 12, 24, 52, 78, 104, and 260
measure: Determine immune response via cytotoxic T-lymphocyte CD8+ (ELISpot)
timeFrame: Baseline; week 52
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: New Haven
country: United States
facility: Yale Center for Clinical Investigation
state: Connecticut
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Salt Lake City
country: United States
facility: University of Utah Pediatric Genetic & Metabolism Clinic
state: Utah
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center, Inc.
state: Virginia
city: Calgary
country: Canada
facility: M.A.G.I.C. Clinic, Ltd.
state: Alberta
Study officials:
References: