Mucopolysaccharidosis type 1H (MPS1H) (Hurler Syndrome) Nutritional, Metabolic, Endocrine Mucopolysaccharidosis, type I
Conditions
Interventions
This is a non-randomized study (each sequentially enrolled participant will receive at least one dose of IMP) of two cohorts and two phases.
Cohort 1 will include six participants aged =12-15 years (a
Sponsors
MiNA Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacodynamic analysis of the study drug MTL-CEBPA: measured using blood samples and urine samples collected at baseline visit and at every visit until the end of the study. PD assessments will include IDUA enzyme activity, amounts of IDUA mRNA, IDUA protein in macrophages/monocytes, peripheral CD 34+ cells and plasma. Concentrations of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate in plasma and urine will also be assessed. Tumor necrosis factor a (TNFa) will also be assessed. 2. Pharmacokinetic analysis of the study drug MTL-CEBPA: plasma and circulating WBC concentrations of CEBPA 51 will be analysed using hybridization-based high-performance liquid chromatography (HPLC) assay in order to determine the PK properties of CEBPA 51 after IV administration of MTL CEBPA. Blood samples will be collected on Weeks 1, 2, 3, 4, 5 (Phase 1 all participants); 7, 9, 11, 13 (Phase 2 QW4 dosing); 7, 9, 11, 13,15, 17 (Phase 2 QW3 dosing); 7, 8, 9, 10, 12, 16 (Phase 2 QW2 dosing). All 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. Exploratory: Clinical outcome/performance assessments will include: 1. Spirometry: forced vital capacity [FVC] and forced expiratory volume in the first second [FEV1]) measured using a spirometer at baseline and at the end of the study 2. Left ventricular ejection fraction/fractional shortening/posterior wall thickness/septum wall thickness/end-systolic diameter/end-diastolic diameter and ejection fraction modified Simpson’s measured using non-invasive echocardiogram at baseline and at the end of the study 3. X-ray of hips and pelvis to measure at a minimum acetabular index, migration percentage, Smith ratio and neck-shaft angle at baseline and at the end of the study 4. 6-minute walk test: measurement of the distance that the participant can walk in 6 minutes on a hard flat surface (only for participants aged 6 years and ab | — |
Countries
United Kingdom
Contacts
Public ContactNagy Habib
Outcome results
None listed