None listed
Conditions
Brief summary
Complications of MPS I include pain and functional symptoms. The aim of the study is to assess the safety of the investigational product pentosan polysulfate (PPS) in patients with MPSI, and to determine if PPS can successfully alleviate pain and functional symptoms in MPS I patients who have received ERT and/or haemopoietic stem cell transplantation (HSCT). Up to 10 participants (males and females aged 5 years or greater who meet the inclusion criteria) are expected to be enrolled. This is an open label study, in which participants will be sequentially assigned to receive either 0.75 mg/kg or 1.5 mg/kg of PPS via subcutaneous injection. PPS will be administered weekly for the first 12 weeks and then every second week until the end of the study. The study will run for 73 weeks from baseline. Following the screening visit, the participants will be required to attend the hospital for assessments out to week 73. Many of the scheduled visits may occur at the patient’s home by a member of the study team. There will be a final study visit involving assessments 5-7 days after the last PPS administration. There will be a final study visit involving assessments 5-7 days after the last PPS administration.
Interventions
Subjects will be sequentially allocated to one of 2 dose cohorts:
• Cohort 1 will receive 0.75 mg/kg of PPS
• Cohort 2 will receive 1.5 mg/kg of PPS
All subjects will receive PPS through subcutaneous injection from Day 1 to Week 72 (i.e., 72 weeks on PPS therapy). For Weeks 1 through 12, dosing will be weekly. From Weeks 14 through 72, dosing will be every other week. Intervention will be administered by a suitably qualified member of the study team, either a nurse or a doctor. Adherence to ther
Subjects will be sequentially allocated to one of 2 dose cohorts: • Cohort 1 will receive 0.75 mg/kg of PPS • Cohort 2 will receive 1.5 mg/kg of PPS All subjects will receive PPS through subcutaneous injection from Day 1 to Week 72 (i.e., 72 weeks on PPS therapy). For Weeks 1 through 12, dosing will be weekly. From Weeks 14 through 72, dosing will be every other week. Intervention will be administered by a suitably qualified member of the study team, either a nurse or a doctor. Adherence to therapy will be recorded by the study team members.
Sponsors
Paradigm Biopharmaceuticals Pty Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
5 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females aged greater than or equal to 5 years 2. Documented diagnosis of MPS I 3. Must have received primary therapy for MPS I (HSCT (Haemopoietic stem cell transplantation) +/- ERT (enzyme replacement therapy)) 4. For subjects receiving ERT, ERT must have been administered at a stable dose 5. Able to walk independently with or without use of an assistive device 6. Subjects must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures Additional inclusion/exclusion criteria apply
Exclusion criteria
1. Documented or reported history of increased bleeding tendency in the presence or absence of anticoagulant or antiplatelet drugs 2. History of idiopathic or immune-mediated (including heparin-induced) thrombocytopenia 3. Current treatment with anticoagulants or antiplatelet drugs, excluding aspirin less than or equal to 100 mg/day 4. Use of opioids or medications on the Prohibited Medications list within 2 weeks of Day 1 and throughout the duration of the study 5. Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of GI tract bleeding 6. Coagulation parameters (activated partial thromboplastin time [aPTT]), outside laboratory reference range, platelets <160,000/µl, or liver function tests (aspartate transaminase [AST], alanine transaminase [ALT]) greater than or equal to 1.5x upper limit of normal range (ULNR) at Screening 7. History or evidence of chondrocalcinosis or fibromyalgia 8. History or evidence of human immunodeficiency virus (HIV), hepatitis B or hepatitis C 9. Major surgery within 12 weeks preceding Day 1 or anticipated surgery in the study period 10. Medical history or evidence of any clinically significant active or chronic condition (with the exception of signs and symptoms relating to MPS I) including autoimmune disease involving musculoskeletal system which in the opinion of the Investigator or Sponsor may impact assessment of safety or efficacy parameters or the validity of study results 11. Current or recent (within 90 days preceding Day 1) immunosuppressive or immune-modulative systemic therapy 12. Any acute illness within 2 weeks of baseline 13. History of untreated drug or alcohol abuse and/or dependence within the 12 months preceding screening 14. Participation in another clinical trial or administration of any investigational product or experimental product within 12 weeks or 5 half-lives (whichever is longer) preceding Day 1 15. History of significant hypersensitivity to PPS or drugs of a similar chemical or pharmacological class 16. Any clinically significant abnormalities (with the exception of abnormalities relating to MPS I) on clinical chemistry, haematology, urinalysis, physical examination, medical history, 12-lead ECG, or vital signs as judged by the investigator which may interfere with participation in study activities
Outcome results
None listed