A Study in MPS VI to Assess Safety and Efficacy of Odiparcil

NCT03370653 | Completed Phase 2 DMC

• 1 other identifier: IVA_01_ODI_HMPS_17_002
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 4

Brief Summary

Mucopolysaccharidoses (MPS) are a group of rare inherited disorders characterized by a deficiency of lysosomal enzymes responsible for the normal degradation of glycosaminoglycans (GAGs). Medical need for treatment of MPS is still very high due to the poor penetration of the recombinant enzymes into the blood brain barrier as well as the ocular barriers and into tissues that are poorly vascularized, such as cartilages and bones. Odiparcil is an orally active compound that allows the synthesis of soluble glycosaminoglycans (GAGs), mainly chondroitin sulfate (CS) and dermatane sulfate (DS). The neosynthesized solubles GAGs are then excreted in urine. By diverting endogenous GAG synthesis to the synthesis of soluble odiparcil linked GAGs, odiparcil should decrease the intracellular pool of GAGs and consequently decrease the lysosomal GAG accumulation. The primary objective of the study is to assess the safety and efficacy of two doses of odiparcil in MPS VI patients and to provide evidence to enable the selection of the relevant dose of odiparcil for phase III study. The secondary objective of this study is to characterize the dose response, PK and PD of odiparcil.

Conditions

Mucopolysaccharidosis VI

Keywords

MPS VI; Lysosomal disease; Glycoaminoglycans (GAG); Odiparcil

Outcome Measures

Primary Outcomes (4)

• Number of patients with modified clinical signs

  Changes in physical examination and vital signs

  26 weeks

• Number of patients with modified biological values

  Change from baseline in laboratory safety tests (coagulation, liver enzymes and crystalluria) 12-lead-ECG and bone biomarkers.

  26 weeks

• Incidence of AEs/SAEs

  Incidence of AEs/SAEs, patient withdrawals from study due to AEs/SAEs,

  26 weeks

• 12-lead ECG

  Change from Baseline in ECG

  26 weeks

Secondary Outcomes (25)

• Mobility: 6-minute walk test

  26 weeks

• Mobility: 9-hole PEG test

  26 weeks

• Mobility: range of motion of the shoulder

  26 weeks

• Pain assessment

  26 weeks

• Respiratory function

  26 weeks

Study Arms (4)

Double-blind - odiparcil 1000 mg per day

EXPERIMENTAL

2 tablets of odiparcil 250 mg per os, twice daily (BID)

Drug: Odiparcil

Double-blind - odiparcil 500 mg per day

EXPERIMENTAL

1 tablet of placebo and 1 tablet of odiparcil 250 mg per os, twice daily (BID)

Drug: Odiparcil; Other: Placebo

Double-blind - placebo

PLACEBO COMPARATOR

2 tablets of placebo per os, twice daily (BID)

Other: Placebo

Open Label - odiparcil 1000 mg per day

EXPERIMENTAL

2 tablets of odiparcil 250 mg per os, twice daily (BID)

Drug: Odiparcil

Interventions

Odiparcil DRUG

Investigational product: odiparcil 250 mg tablets

Double-blind - odiparcil 1000 mg per day; Double-blind - odiparcil 500 mg per day; Open Label - odiparcil 1000 mg per day

Placebo OTHER

Comparator: placebo tablets similar to odiparcil 250 mg tablets

Double-blind - odiparcil 500 mg per day; Double-blind - placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients with MPS Type VI receiving enzyme replacement therapy (Naglazyme) for at least 6 months on the licensed dosage or as per local guidelines.
• Patients with MPS Type VI not receiving enzyme replacement therapy for the following reasons:
• Patients previously treated with ERT but have discontinued for more than 3 months either due to medical decision or personal choice
• Patients allergic to ERT therapy
• Patients that have had a previous hematopoietic stem cell transplant (HSCT)
• Patients not treated with ERT i.e. treatment naïve

You may not qualify if:

• 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.
• 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.
• Subjects who had surgery within 3 months before study starts, or for whom surgery is planned during study period.
• Patient with spinal cord compression requiring surgical intervention.
• Subjects with the following liver test anomalies: any ALT, AST \> 3xULN or bilirubin \>1.5xULN (except if Gilbert syndrome) at screening visit.
• Evidence of an immunosuppressive state, including known HIV infection, agammaglubilinemias, T-Cell deficiencies.
• Subjects with history of chronic infections, including but not limited to subjects with past 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.
• History of malignant cancer except of cervical carcinoma in situ, basal cell carcinoma, dermatological squamous cell carcinoma.
• Subjects with significant haematologic abnormalities, such as haemoglobin \<8 g/dL, or WBC\<2000 /mm3 or absolute neutrophil count \<1300 /mm3, or platelet \<30.000 /mm3.
• International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) or thrombin time (TT) values above the laboratory reference range at screening. For patients on anti-coagulants, they should be within their target effect on INR and be stable.
• Any history of bleeding diathesis
• Patient with coexistence of corneal pathologies other than corneal clouding (e.g. exposure keratopathy)
• 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.
• An unwillingness on the part of female patients to use highly effective form of birth control2 if engaging in sexual intercourse and to have a monthly pregnancy test during treatment and until completion of follow-up procedures.
• Pregnant or lactating women.

Sponsors & Collaborators

• Inventiva Pharma: lead

Study Sites (4)

Hôpital Femme-Mère-Enfant

Bron, 69500, France

Location

Villa Metabolica

Mainz, 55131, Germany

Location

Centro Hospitalar S. João

Porto, 4200-319, Portugal

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis VI

Interventions

odiparcil

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Derralynn HUGHES, MD

  Royal Free Hospital, London UK

  PRINCIPAL INVESTIGATOR

• Julia HENNERMANN, MD

  Villa Metabolica, Mainz GERMANY

  PRINCIPAL INVESTIGATOR

• Nathalie GUFFON-FOUILHOUX, MD

  Hôpital Femme-Mère-Enfant

  PRINCIPAL INVESTIGATOR

• Elisa LEAO-TELES, MD

  Centro Hospitalar S. João, Porto, Portugal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Preliminary safety assessment (N=2): an open-label, escalating dose (2 doses) study. Core study: conducted on 2 populations in parallel: * A first cohort (N=18): MPS VI patients receiving ERT assigned in 3 arms: * Placebo (N=6) * Odiparcil 500 mg per day (250 mg BID) (N=6) * Odiparcil 1000 mg per day (500 mg BID) (N=6). * A second cohort (N=6): MPS VI patients not receiving ERT (odiparcil 1000 mg per day (500 mg BID)).

Study Record Dates

• First Submitted: November 23, 2017
• First Posted: December 12, 2017
• Study Start: December 30, 2017
• Primary Completion: September 24, 2019
• Study Completion: October 22, 2019
• Last Updated: November 1, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); GB (1); PT (1); DE (1)