HMI-203 for Hunter Syndrome

No longer recruiting at 5 trial locations

Overseen By Tracy McGregor, M.D.

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Homology Medicines, Inc

Must be taking: Idursulfase ERT

Must not be taking: Corticosteroids, Tacrolimus

Disqualifiers: Multiple sulfatase disorder, BMT, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called HMI-203 to determine its safety and effectiveness in treating MPS II, also known as Hunter syndrome. MPS II is a rare genetic disorder that disrupts the breakdown of certain substances in the body. The trial targets individuals already receiving enzyme replacement therapy (ERT). Participants will receive a single dose of the gene therapy and undergo monitoring for five years. Eligible participants are males who have lived with MPS II, have used ERT for at least a year, and have stable health conditions. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires participants to be on regular enzyme replacement therapy (ERT) for MPS II. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that HMI-203 is likely to be safe for humans?

Research has shown that HMI-203 is safe in early animal studies. In these studies, both mice with MPS II (Hunter syndrome) and healthy mice tolerated the treatment well. This outcome gave researchers enough confidence to begin testing HMI-203 in humans.

Since this trial is in its first phase, the main goal is to ensure the treatment's safety for humans. At this stage, researchers closely monitor participants for any side effects. Because HMI-203 is still in the early stages of human testing, more information is needed to fully understand its safety. However, reaching this phase suggests that earlier tests did not reveal major safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

HMI-203 is unique because it offers a potentially transformative approach for treating MPS II, also known as Hunter syndrome. Unlike the current standard enzyme replacement therapies (ERTs) that require regular infusions, HMI-203 is a gene therapy designed to deliver a functional copy of the IDS gene directly to cells. This could provide a long-lasting solution by allowing the body to produce the needed enzyme itself, reducing or even eliminating the need for frequent treatments. Researchers are excited about HMI-203 because it targets the root cause of the disease, potentially leading to more consistent and sustained improvements in patients' symptoms.

What evidence suggests that HMI-203 might be an effective treatment for MPS II?

Research shows that HMI-203, a gene therapy for Hunter syndrome (MPS II), aims to help the body produce the I2S enzyme. This enzyme breaks down harmful substances called glycosaminoglycans (GAGs), which accumulate in people with MPS II. In earlier studies on mice, HMI-203 was well tolerated and showed promise in reducing these harmful substances. Although human studies have provided limited information, these findings offer hope that HMI-203 could effectively address the enzyme deficiency in MPS II. Ongoing research in this trial, which includes different dose levels of HMI-203, will provide more insight into its potential benefits for patients. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

You have been in good health for the past year, with no significant problems with urination, walking, or heart and lung function.

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

Exclusion Criteria

Presence of anti-capsid neutralizing antibodies

ALT or AST > ULN; Total or Direct bilirubin > ULN

You have undergone a bone marrow transplant, stem cell transplant, or gene therapy in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IV infusion of HMI-203 gene therapy

1 day

1 visit (in-person)

Dose Escalation

Participants are enrolled in one of three dose cohorts with intervals for safety and efficacy review

60 days for first cohort, 21 days for subsequent cohorts

Follow-up

Participants are monitored for safety and efficacy after treatment

5 years

Most frequent visits occur in the first year

What Are the Treatments Tested in This Trial?

Interventions

• HMI-203

How Is the Trial Designed?

Group I: HMI-203 Low Dose Level Cohort 1 Experimental Treatment 1 Intervention

Group II: HMI-203 Intermediate Dose Level Cohort 2 Experimental Treatment 1 Intervention

Group III: HMI-203 High Dose Level Cohort 3 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Homology Medicines, Inc

Lead Sponsor

Trials

6

Recruited

12,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05238324?cond=hunters%20syndrome&checkSpell=&rank=6

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

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949774423000171

juMPStart: Phase 1, open-label, dose-escalation safety and ... Nonclinical safety studies demonstrated that HMI-203 was well tolerated in the MPS II and WT mouse models. These data supported evaluating HMI-203 in clinical ...

3. researchgate.net researchgate.net/profile/Laura-Lopez-De-Frutos/publication/367799809_A_novel_enzymatic_diagnosis_method_of_lysosomal_diseases/links/63e5feecc002331f7268a520/A-novel-enzymatic-diagnosis-method-of-lysosomal-diseases.pdf

Clinical trial design for HMI-203 investigational gene ... Here we describe data from a murine MPS II model demonstrating effective gene ... Results: As of 31 May 2021, 20 patients are enrolled: 19 in the treated ...

4. cgtlive.com cgtlive.com/view/homology-medicines-anticipating-gene-therapy-data-updates-pku-hunter-syndrome

Homology Medicines Anticipating Gene Therapy Data ... HMI-203 is an investigational gene therapy intended to treat mucopolysaccharidosis II (MPS II; Hunter syndrome). It uses one of the company's ...

5. biospace.com biospace.com/homology-medicines-initiates-clinical-trial-for-hmi-203-a-one-time-investigational-gene-therapy-candidate-for-adults-with-mps-ii-hunter-syndrome

Homology Medicines Initiates Clinical Trial for HMI-203, a ... HMI-203 is developed to enable the production of the I2S enzyme that is responsible for breaking down glycosaminoglycans (GAGs), which ...

6. gimopen.org gimopen.org/article/S2949-7744(23)00017-1/pdf

Phase 1, open-label, dose-escalation safety and efficacy ... Nonclinical safety studies demonstrated that HMI-203 was well tolerated in the MPS II and WT mouse models. These data supported evaluating HMI-203 in clinical ...

7. firstwordpharma.com firstwordpharma.com/story/5497105

Homology Medicines Announces Presentations on HMI ... In oral platform presentations, key eligibility criteria and planned endpoints for the juMPStart trial were discussed and data from the HMI-203 ...