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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
Pentosan Polysulfate Sodium (PPS) in subjects with mucopolysaccharidosis type I (MPS I)
Scientific title
An open-label single-centre pilot study to evaluate the safety and tolerability of pentosan polysulfate sodium in subjects with mucopolysaccharidosis type I (MPS I)
Secondary ID [1] 300897 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mucopolysaccharidosis type I (MPS I)
316830 0
Condition category
Condition code
Metabolic and Endocrine 315041 315041 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 315173 315173 0 0
Other human genetics and inherited disorders

Study type
Description of intervention(s) / exposure
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 48 (i.e., 48 weeks on PPS therapy). For Weeks 1 through 12, dosing will be weekly. From Weeks 14 through 48, 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
Intervention code [1] 317217 0
Treatment: Drugs
Comparator / control treatment
Safety and efficacy of both dose cohorts will be analysed as well as a comparison between the two cohorts.

0.75mg/kg will be the reference comparator
Control group
Dose comparison

Primary outcome [1] 323342 0
To evaluate the safety of PPS in subjects with MPS I based on incidence of treatment-emergent adverse events including serious adverse events and change from baseline in clinical laboratory data. Adverse events are rare and may include bleeding issues, assessed by observation and blood samples, cardiac events, monitored by ECG and vital signs, injection site reactions, assessed through observation, nausea through self-report
Timepoint [1] 323342 0
Safety parameters will be recorded every week for the first 12 weeks then every 2 weeks there-after through week 49.
Secondary outcome [1] 381613 0
Pain, measured by PROMIS pain interference and pain intensity (numeric rating scale) short forms
Timepoint [1] 381613 0
Measured at weeks 6, 13, 25, 37, 49
Secondary outcome [2] 381931 0
Mobility, measured by PROMIS fatigue, mobility short forms, 6minute walk test, and Gait, Stair, Gower, Chair (GSGC) test
Timepoint [2] 381931 0
Measured at weeks 6, 13, 25, 37, 49
Secondary outcome [3] 381932 0
Pain behavior as measured by the PROMIS Pain Behavior short form
Timepoint [3] 381932 0
Measured at weeks 6, 13, 25, 37, 49
Secondary outcome [4] 381933 0
Joint range of motion, measured by standard goniometer (shoulder and knee)
Timepoint [4] 381933 0
Measured at weeks 6, 13, 25, 37, 49
Secondary outcome [5] 381934 0
Global impression of change, as measured on a 7-point scale from ‘no change’ to ‘a great deal better’
Timepoint [5] 381934 0
Measured at weeks 13, 25, 37, 49
Secondary outcome [6] 381936 0
Exploratory: Pulmonary function as measured by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) assessed by spirometry
Timepoint [6] 381936 0
Measured at weeks 25, 49
Secondary outcome [7] 381937 0
Exploratory: Grip strength as measured by digital hand dynamometer
Timepoint [7] 381937 0
Measured at weeks 6, 13, 25, 37, 49
Secondary outcome [8] 381938 0
Exploratory: Biomarkers (on the inflammatory biomarkers matrix metalloproteinase 3 (MMP3), A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4, ADAMTS 5, C-terminal telopeptide of type I collagen (CTX-I), C-terminal telopeptide of type II collagen (CTX-II), cartilage oligomeric matrix protein (COMP), TNF-a, interleukin (IL)-8, macrophage inflammatory protein (MIP)-1 a, tissue inhibitor of metalloproteinases (TIMP)-1, vascular endothelial growth factor (VEGF), and migration inhibitory factor (MIF)-1) as measured by serum assay
Timepoint [8] 381938 0
Measured at weeks 13, 25, 49
Secondary outcome [9] 381939 0
Exploratory: Urinary glycosaminoglycan (GAG) levels
Timepoint [9] 381939 0
Measured at weeks 3, 25, 49
Secondary outcome [10] 381940 0
Exploratory: Pharmacokinetics – as measured by CMAX, TMAX, AUC, half life (and other measures) in plasma samples
Timepoint [10] 381940 0
Measured at weeks 1 and 4, before injection and at hours 2, 4 and 24
Secondary outcome [11] 384331 0
Endurance, measured by PROMIS fatigue, mobility short forms, 6minute walk test
Timepoint [11] 384331 0
Weeks 6, 13, 25, 37, 49
Secondary outcome [12] 384332 0
Upper extremity function measured by the PROMIS Upper Extremity form and the 9-Hole Peg Test
Timepoint [12] 384332 0
Weeks 6, 13, 25, 37, 49
Secondary outcome [13] 384333 0
Function (general) as measured by the SF-36 and the Pediatrics Outcomes Data Collection Instrument (PODCI) questionnaires
Timepoint [13] 384333 0
Weeks 6, 13, 25, 37, 49
Secondary outcome [14] 384334 0
Quality of Life, assessed by the PODCI and the SF-36
Timepoint [14] 384334 0
Weeks 6, 13, 25, 37, 49

Key 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
Minimum age
5 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key 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

Study design
Purpose of the study
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?

Intervention assignment
Other design features
Phase 1 / Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 305347 0
Commercial sector/Industry
Name [1] 305347 0
Paradigm Biopharmaceuticals Pty Ltd
Address [1] 305347 0
Address Level 2, 517 Flinders Lane, Melbourne Vic 3000
Country [1] 305347 0
Primary sponsor type
Commercial sector/Industry
Paradigm Biopharmaceuticals Pty Ltd
Address Level 2, 517 Flinders Lane, Melbourne Vic 3000
Secondary sponsor category [1] 305717 0
Name [1] 305717 0
Address [1] 305717 0
Country [1] 305717 0

Ethics approval
Ethics application status
Ethics committee name [1] 305679 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [1] 305679 0
WCHN Human Research Ethics Committee
2nd Floor Samuel Way Building
72 King William Rd
Ethics committee country [1] 305679 0
Date submitted for ethics approval [1] 305679 0
Approval date [1] 305679 0
Ethics approval number [1] 305679 0

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 49 weeks from baseline. Following the screening visit, the participants will be required to attend the hospital for assessments out to week 49. 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.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 101202 0
Dr David Ketteridge
Address 101202 0
Women’s and Children’s Hospital, Adelaide
72 King William Road
North Adelaide 5006
South Australia
Country 101202 0
Phone 101202 0
+61 8 8161 6610
Fax 101202 0
Email 101202 0
Contact person for public queries
Name 101203 0
Ms Sharon G Charles
Address 101203 0
Paradigm Biopharmaceuticals Ltd
Level 2, 517 Flinders Lane, Melbourne Vic 3000
Country 101203 0
Phone 101203 0
+61 434 553 011
Fax 101203 0
Email 101203 0
Contact person for scientific queries
Name 101204 0
Dr Ravi Krishnan
Address 101204 0
Paradigm Biopharmaceuticals Ltd
Level 2, 517 Flinders Lane, Melbourne Vic 3000
Country 101204 0
Phone 101204 0
+61 434 553 011
Fax 101204 0
Email 101204 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results