Mucopolysaccharidosis type I (alpha-L-Iduronidase deficiency) MedDRA version: 17.0 Level: LLT Classification code 10056888 Term: Mucopolysaccharidosis IS System Organ Class: 100000004850 MedDRA version: 17.0 Level: LLT Classification code 10056887 Term: Mucopolysaccharidosis IH/S System Organ Class: 100000004850 MedDRA version: 17.0 Level: LLT Classification code 10028094 Term: Mucopolysaccharidosis IH System Organ Class: 100000004850
Conditions
Interventions
Trade Name: Pentosan Polysulfat SP 54® injection solution
Product Name: Pentosan Polysulphate SP54®
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PENTOSAN POLYSULFATE SODIUM
CAS Num
Sponsors
Multiplex Pharma Holdings LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female. 2. Age =18 years. 3.Diagnosed as having Mucopolysaccharidosis Type I (alpha-L-Iduronidase deficiency) and have been treated with enzyme replacement therapy (ERT) for a minimum of 24 months. 4. Joint pain and/or reduced joint range of motion at time of enrolment according to the investigator. 5. Written informed consent upon enrolment. 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 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of hypersensitivity to pentosan polysulfate or any of the excipients. 2. Known allergic reaction to heparin or pentosan polysulfate e.g. heparin induced thrombocytopenia. 3. Clinically relevant concomitant severe condition (with the exception of signs and symptoms relating to MPSI) e.g. gastrointestinal (including gastrointestinal ulcerations, polyps, or diverticula), renal, hepatic (ALT and/or AST >10 times upper limit of reference range), pancreatic, pulmonary, cardiovascular (including endocarditis lenta), aneurysm, cerebral hemorrhage, hematological (including thrombocytopenia, hemophilia, hemorrhagic diathesis), endocrinological, suspected tumors with risk of bleeding, neurological, or psychiatric conditions in the opinion of the investigator. 4. Planned invasive procedure other than blood sampling. 5. History of or planned bone marrow transplant. 6. Clinically relevant abnormal laboratory test results including liver enzymes, thrombocytopenia, prolonged clotting time. 7. Intake of anti-inflammatory agents e.g. corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) other than ibuprofen or paracetamol within 10 half lives (t½) of the drug prior to first dosing and throughout the study. 8. Intake of anti-thrombotic agents e.g. heparin, tissue plasminogen activator (t-PA), streptokinase, aspirin within 10 half lives (t½) of the drug prior to first dosing and throughout the study. Coumarin anticoagulants are permitted. 9. Known history or presence of alcohol or substance abuse. 10. Known hepatitis B or C or human immunodeficiency virus (HIV) or syphilis seropositivity. Note: testing for hepatitis and HIV will be performed as part of the screening procedures. 11. For females: pregnancy or lactation. 12. For females of childbearing potential: not willing and able to use a contraceptive method, which the investigator considers reliable. Reliable methods for women are hormonal contraceptives, surgical intervention (e.g. tubal ligation), intrauterine device (IUD) and sexual abstinence. Women must use a reliable method from 6 weeks before the first administration of study medication until 3 weeks after the last administration of the study medication. 13. Participation in another clinical study involving a new chemical entity within 3 months and for studies involving biologicals 6 months prior to enrolment in this study. 14. The subject has received vaccination(s) within 1 month prior to enrollment, or is unwilling to postpone vaccinations for the duration of the study. 15. Subjects who are unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the safety of weekly subcutaneous injections of 1 mg/kg and 2 mg/kg body weight Pentosan Polysulphate SP54® in the treatment of Mucopolysaccharidosis Type I.;Secondary Objective: To investigate the effect of pentosan polysulfate (PPS) on: - 6 minute walk test - pulmonary function - grip test - quality of life - pain intensity - range of motion - inflammatory biomarkers - glycosaminoglycan (GAG) - CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) - measurement of pentosan polysulfate ;Primary end point(s): Safety 1. aPTT and INR 2. Platelet count (thrombocytes) 3. Clinical laboratory parameters: sodium, potassium, calcium, glucose, urea, creatinine, total bilirubin, AST(SGOT), ALT (SGPT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), creatinine kinase (CK), total protein, Troponin I and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) 4. Hematology parameters: hemoglobin, red blood cell count (erythrocytes), hematocrit, total white blood cell count (leucocytes) 5. Adverse events and concomitant medication documented 6. Vital signs (pulse rate, blood pressure, body temperature) documented 7. General medical examination 8. ECG ;Timepoint(s) of evaluation of this end point: Ad 1.: at screening, and pre-dose (immediately before start of ERT iv infusion) and 2 hours after subcutaneous injection and at Day 2 and 1 week (Week 25) and 3 weeks (Week 27) after the last dose of PPS. Ad 2.: at screening, pre-dose at every visit and at Day 2 and 1 week and 3 weeks after the last dose of PPS. Ad 3.: at screening, baseline, Week 12 and Week 25. Ad 4.: at screening, Week 12 and Week 25. Ad 5.: at every visit. Ad 6.: at every visit. Ad 7.: at screening and at Week 25. Ad 8.: at screening and at Week 25. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in cytokines TNF-alpha, IL-1 and glycosaminoglycan (GAG) 2. Change from baseline in 6 minute walk test 3. Change from baseline in pulmonary function tests measured in the morning 4. Change from baseline in Grip Test 5. Change from baseline in CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) 6. Change from baseline in SF 36 Quality of Life 7. Change from baseline in pain assessment measured using Brief Pain Inventory 8. Change from baseline in range of motion measured by gait analysis 9. Pentosan polysulfate plasma concentrations measured pre-dose and 2 hours post-dose ;Timepoint(s) of evaluation of this end point: Ad. 1. - 8.: at Week 12 and at Week 25. Ad 9.: at Day 1, Week 2, Week 6, Week 10, Week 14, Week 18, Week 24 and once at Day 2 and Week 27. | — |
Countries
Germany
Contacts
Public ContactKlaus Maag, MD
bene pharmaChem GmbH & Co. KG
Outcome results
None listed