A study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of MTL-CEBPA in children with mucopolysaccharidosis type IH

Phase 1

• Conditions: Mucopolysaccharidosis type 1H (MPS1H) (Hurler Syndrome); Nutritional, Metabolic, Endocrine; Mucopolysaccharidosis, type I

• Registration Number: ISRCTN10369994
• Lead Sponsor: MiNA Therapeutics Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-02-24
• Last Update Posted: 1 May 2023
• Study Completion: 2025-04-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Verbal assent will be obtained from the participant as well as written informed consent from the parent/legal guardian prior to any study specific procedure
2. Male or female participants aged =12-16 years (Cohort 1), or =4-11 years (Cohort 2) with a biochemical and genetic diagnosis of MPS-1H
3. Minimum 6 months post HSCT
4. Off immunosuppression, including corticosteroids for at least 4 weeks prior to study
5. Stable myeloid chimerism (>80% donor cells as determined by short tandem repeats [STR] in )
6. Anticipated life expectancy in excess of the study period
7. Not enrolled in any other interventional study
8. Acceptable laboratory parameters , consistent with participant age and MPS-1H diagnosis
9. Negative blood pregnancy test for females of childbearing potential within 10 days prior to the first drug administration
10. For female participants of child-bearing potential, agreement to be abstinent or use highly effective contraception (defined as method(s) that result in a failure rate of <1% per year) in females of childbearing potential during the entire study and defined post-study period
11. Willingness and ability to comply with all protocol requirements including scheduled visits, treatment plans, laboratory tests and other study procedures

Exclusion Criteria

1. Participants who received investigational drug(s) within the last 30 days (or 5 half-lives if longer) prior to study treatment initiation
2. Participants receiving laronidase at commencement of study (minimum 6 weeks wash out)
3. Major surgery within the last 30 days prior to study treatment initiation, or planned within the study period
4. Pregnant or lactating women
5. Known hypersensitivity to the active substance (MTL-CEBPA) or to any of the excipients, not managed by conventional approaches. Excipients include: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC); 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); Cholesteryl hemisuccinate (CHEMS); and Cholesteryl-4-[[2-(4-morpholinyl)ethyl]amino]-4-oxobutanoate (MOCHOL)
6. Any other condition (e.g., known or suspected poor compliance, etc.) that, in the judgment of the investigator, may affect the participant’s ability to follow the protocol specific procedures

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety (primary): Safety will be assessed by monitoring of AEs graded according to toxicity criteria (CTCAE v5.0), measurement of vital signs (inc. blood pressure, pulse, body temperature, and respiratory rate), 12-lead electrocardiograms (ECGs) and safety laboratory data (including. haematology, coagulation, clinical chemistry, urinalysis, and complement activation [complement fragments C3a and Bb]). Chimerism will also be routinely assessed. A description of both participant and investigator assessment of tolerability will be collected. AEs will be collected throughout the study, from informed consent until the end of study visit. All other measurements will be taken from the screening visit, all the way through the study at set study visits and at the follow-up/early termination visit.