Mucopolysaccharidosis (MPS) type VI. MedDRA version: 20.1 Level: PT Classification code 10028095 Term: Mucopolysaccharidosis IV System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Odiparcil
Product Code: IVA 336
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Odiparcil
CAS Number: 137215-
Sponsors
Inventiva S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female gender. 2. Age =16 years. 3. Diagnosis of MPS VI. 4. Urine GAG above upper limit of normal (ULN) based on historical data. 5. Willing and able to provide written, dated, signed informed consent, or in the case of subjects age =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria for the entire cohort 1. Use of any investigational product or investigational medical device within 30 days prior to screening. This will include product bought over the counter specifically compounds like genistein and pentosane polysulphate which may not be considered as investigational products by patients and some health care professionals. 2. Concurrent disease or condition that would interfere with study participation or pose a safety concern for example patient with: severe cardiac insufficiency as define NYHA class > II, and severe restrictive chronic respiratory insufficiency as reflected by serum [HCO3-] =28 mEq/L. 3. Subjects who had surgery within 3 months before study starts, or for whom surgery is planned during study period. 4. Patient with spinal cord compression requiring surgical intervention. 5. Subjects with the following liver test abnomalies: any ALT, AST > 3 x ULN or bilirubin >1.5 x ULN (except if Gilbert syndrome) at screening visit. 6. Evidence of an immunosuppressive state, including known HIV infection, agammaglubilinemias, T-Cell deficiencies. 7. Subjects with history of chronic infections, including but not limited to subjects with history of viral hepatitis C, or B, with recent history of serious or life-threatening infection or any current signs or symptoms that may indicate infection at visit V-1 of study as per investigators clinical judgement. 8. History of malignant cancer except of cervical carcinoma in situ, basal cell carcinoma, dermatological squamous cell carcinoma. 9. Subjects with significant haematologic abnormalities, such as hemoglobin <8 g/dL, or WBC<2000 /mm3 or absolute neutrophil count <1300 /mm3, or platelet <30.000 /mm3. 10. International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) or thrombin time (TT) values above the central laboratory reference range at screening considered as clinically significant by the investigator. For patients on anti-coagulants, they should be within their target effect on INR and be stable. 11. Any history of bleeding diathesis. 12. Patient with coexistence of corneal pathologies other than corneal clouding (e.g. exposure keratopathy) 13. An unwillingness on the part of male patients to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness to use highly effective form of birth control if engaging in sexual intercourse with a woman who could become pregnant from the time of the first dose of study medication until completion of follow-up procedures. 14. An unwillingness on the part of female patients to use highly effective form of birth control if engaging in sexual intercourse and to have a monthly pregnancy test during treatment and until completion of follow-up procedures. 15. Pregnant or lactating women. 16. Have a known hypersensitivity to any of the ingredients or excipients of the IMP including: Microcrystalline Cellulose, Povidone, Sodium starch glycolate (type A), Magnesium stearate, Opadry™ II 85F18422 Exclusion criteria for ERT treated group: 1. Previous hematopoietic stem cell transplant (HSCT)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Preliminary safety assessment The goal of preliminary safety assessment is to focus on clinical tolerance and lab safety such as coagulation, liver enzymes and cristalluria. 2. Core study a. Safety outcomes: a1. Safety outcomes will be evaluated on the following safety variables: incidence of AEs/SAEs, patient withdrawals from study due to AEs/SAEs, change from baseline in laboratory safety test, change from baseline in vital signs parameters. a2.1 Twelve-lead-ECG a2.2 Bone biomarkers (osteocalcin, beta-crosslaps, bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP)). b. Efficacy outcomes: b1. Mobility: 6-minute walk test, 9-hole PEG test, range of motion of the shoulder b2. Pain assessment: Brief Pain Inventory BPI b3. Respiratory function: FEV1, FVC, MVV b4. Cardiac and vascular tests: echochardiogram and carotid intima media thickness b5. Audiology assessments: pure tone audiometry and whisper voice test b6. Ophthalmology assessments: corneal opacification, level of retinopathy and optic nerve involvement, intra-ocular pressure, and visual acuity b7. Questionnaires: EQ-5D-5L, Zarit caregiver burden, Fatigue Severity Scale c. Pharmacokinetic endpoints: c1. Odiparcil concentration in plasma and its metabolites. c2. Pre-dose samples will be collected to measure the odiparcil concentration remaining c3. Metabolite identification ? d. Pharmacodynamic endpoints: d1. GAG concentrations in urine and leukocytes isolated from peripheral blood d2. GAG content in skin biopsies d3. Anti-thrombin IIa activity in plasma d4. Thrombin gene | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
France, Germany, Portugal, United Kingdom
Contacts
Public ContactVéronique BERGER
Inventiva S.A
Outcome results
None listed