Study to investigate the fate of odiparcil since its administration up to the point is completely eliminated, its safety and efficacy in patients 16 years and above with mucopolysaccharidosis (MPS) type VI

Phase 1

• Conditions: Mucopolysaccharidosis (MPS) type VI.; MedDRA version: 20.1Level: PTClassification code 10056892Term: Mucopolysaccharidosis VISystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

• Registration Number: EUCTR2017-002158-35-DE
• Lead Sponsor: Inventiva S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-16
• Study Completion: 2019-10-22
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Male or female gender.
2. Age =18 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, after the nature of the study has been explained, and prior to any research-related procedures or study assessment.
6. Able to comply with all study procedures.
7. Women with childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must agree to use a highly effective method of birth control during the study and at least 4 weeks after last administration.The following can be considered to be examples of highly effective methods of contraception preferably with low user dependency:
- combined (estrogen and progestogen containing) hormonal contraception associated wiht inhibition of ovulation (oral, intravanginal or transdermal)
- progestogen-only hormonal contraceptioni associated with inhibition of ovulation (oral, injectable, implantable) 1
- Intrauternine device (IUD) 1
- Intrauterine hormone-releasing system (IUS) 1
- Bilateral tubal occulusion 1
- Vasectomised partner 1
- Sexual abstinence
These methods of contraception must be supplemented with a barrier method (preferably male condom).

1 Contraception methods that are considered to have low user dependency.

Inclusion criteria for Enzyme Replacement Therapy (ERT) receiving group
1. Patients with MPS Type VI receiving enzyme replacement therapy (Naglazyme) for at least 6 months on the licensed dosage or as per local guidelines.

Inclusion criteria for not ERT receiving group:
Patients with MPS Type VI not receiving enzyme replacement therapy for the following reasons:
1. Patients not treated with ERT (treatment naive) or previously treated with ERT but having discontinued for more than 3 months before inclusion, either due to medical decision or personal choice (e.g. for quality of life preferences). Under no circumstances patients will be taken of ERT for the only purpose of participating to the study. Reason for not receiving ERT should be specified by the invetigator.
2. Patients allergic to ERT therapy
3. Patients that have had a previous hematopoietic stem cell transplant (HSCT)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
Subjects with other haematological abnormalities not corresponding to the above criteria should not be included in preliminary safety assessment.
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 anticoagulants, 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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified