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Trial registered on ANZCTR


Trial ID
ACTRN12617000893303
Ethics application status
Approved
Date submitted
14/06/2017
Date registered
19/06/2017
Date last updated
20/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A pilot study to investigate the effects of pentosan polysulfate sodium in Ross River virus induced arthralgia
Scientific title
A pilot study to investigate the effects of pentosan polysulfate sodium in Ross River virus induced arthralgia
Secondary ID [1] 291932 0
none
Universal Trial Number (UTN)
Trial acronym
PARA_004
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ross River Virus induced arthralgia 303266 0
Condition category
Condition code
Musculoskeletal 302692 302692 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 302693 302693 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Pentosan polysulfate sodium for injection, 100 mg/ml.
Arm 2: 0.9% NaCl for injection.

Treatment (active or placebo) will be administered by sub-cutaneous injection, in a randomised, double blinded manner by trained clinical trial staff at clinical trial sites, in a ratio of 2:1 active:placebo.

Drug accountability logs will be maintained and monitored throughout the study.

The dosage regime is 2mg/kg (or equivalent volume of placebo) by subcutaneous injection, twice weekly, for 6 weeks.
Intervention code [1] 298054 0
Treatment: Drugs
Comparator / control treatment
Placebo control 0.9% NaCl for injection
Control group
Placebo

Outcomes
Primary outcome [1] 302232 0
Treatment-emergent adverse events (TEAEs) including Serious Adverse Events (SAEs), collected by symptoms reported in response to questioning at each visit (twice weekly), clinically significant laboratory abnormalities, physical examination findings.
Timepoint [1] 302232 0
Day 1 of Treatment to end of study (day 81)
Primary outcome [2] 302234 0
Safety - Changes in blood results (haematology panel including Haemoglobin, haematocrit, red blood cell count, differential white blood cell count, platelet count, mean corpuscular haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin concentration)
Timepoint [2] 302234 0
Day 1, 15, 29, 39 and 81
Primary outcome [3] 302235 0
safety - Changes in blood results (biochemistry)
Glucose, sodium, potassium, chloride, bicarbonate, calcium creatinine, urea, uric acid, amylase, lipase, triglyceride, cholesterol, total protein, lactate dehydrogenase, creatinine kinase, C-reactive protein, albumin, phosphate, Aspartate aminotransferase, Alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, conjugated bilirubin, total bilirubin.
Timepoint [3] 302235 0
Day 1, 39 and 81
Secondary outcome [1] 335248 0
Change from baseline in patient assessed Quality of Life scores as assessed by SF-36 scores
Timepoint [1] 335248 0
Day 1, 15, 29, 39 and 81
Secondary outcome [2] 335249 0
Change from baseline in RAPID 3 scores (self assessed patient questionnaire to assess joint symptoms)
Timepoint [2] 335249 0
Day 1, 15, 29, 39 and 81
Secondary outcome [3] 335250 0
Change from baseline in pain intensity score as assessed by the Numeric Rating Scale (NRS) for pain
Timepoint [3] 335250 0
Day 1, 15, 29, 39 and 81
Secondary outcome [4] 336068 0
Changes in Coagulation (measured by APTT and INR)
(Primary outcome)
Timepoint [4] 336068 0
Day 1, 15, 29, 39, 81

Eligibility
Key inclusion criteria
1. Males and females aged 18 - 65 years (inclusive)
2. Confirmed diagnosis of Ross River virus infection based on laboratory definitive diagnosis according to Australian Government Ross River virus case definition
3. Clinical symptoms of Ross River virus infection including a minimum 2 joints involved (swollen and/or tender joint on examination)
4. The onset of RRV infection symptoms minimum 12 weeks and maximum 36 weeks prior to Day 1
5. Able to speak, read and understand English sufficiently to understand the purposes and risks of the study and to provide written informed consent
6. If applicable, subjects must be willing to comply with the medically acceptable contraceptive requirements of the study from Screening to at least 28 days after the last IMP administration
7. Body Mass Index (BMI) of 18.0 to 35.0 kg/m2 (inclusive)
Subjects must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Documented or reported bleeding tendency with anticoagulant or antiplatelet drugs
2. Current treatment with anticoagulants or antiplatelet drugs
3. Subject taking non steroidal anti-inflammatory drugs (NSAIDS) or opioids within 2 weeks of Day 1 or any medication as per Prohibited Medications. (Note rescue paracetamol maximum 4 g/day is permitted)
4. Subject unwilling to withhold paracetamol and alcohol for 24 hours prior to study assessment visits
5. Any clinically significant abnormalities not related to RRV infection on clinical chemistry, haematology, urinalysis, physical examination, medical history, 12-lead ECG, or vital signs as judged by the investigator or sponsor (at Screening and/or Day 1)
6. Coagulation parameters or platelets outside normal range at Screening and/or Day 1
7. History or evidence of, or positive test for HIV, hepatitis B or hepatitis C
8. Evidence of any active or clinically significant chronic condition including autoimmune disease involving the musculoskeletal system
9. Current evidence or recent history of other arthrogenic virus infection
10. Current or recent (within 90 days prior to Day 1) immunosuppressive or immunomodulative therapy, including intra-articular corticosteroid injection and systemic corticosteroids
11. Blood or plasma donation of more than 500 mL during the 3 months prior to Day 1
12. Currently hospitalised or any planned hospitalisations during the study period
13. History of drug or alcohol abuse and/or dependence within the six months prior to Day 1
14. Participation in another clinical trial or administration of any investigational agent within 8 weeks or 5 half-lives (whichever is longer) prior to Day 1
15. Currently active or recent history (within previous 12 months) of a gastric or duodenal ulcer, or suspicion of alimentary tract bleeding
16. History of significant hypersensitivity to PPS or drugs of a similar chemical or pharmacological class, including a history of heparin induced thrombocytopenia
17. Females who are breast feeding, pregnant or planning to become pregnant during participation in the study
18. Major surgery within 3 months prior to Day 1 or anticipated surgery in the study period
19. History of or current clinically-significant gastrointestinal, hepatic, renal, cardiovascular, respiratory, endocrine, oncological, immunological, neurological, ophthalmological, haematological or psychiatric disorder or any other condition, which in the opinion of the investigator or sponsor would jeopardize the safety of the subject or the validity of the study results


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
No formal statistical sample size estimation has been performed due to the exploratory nature of this study. Sample size is based on clinical and practical considerations.

The descriptive summary for the categorical variables will include counts and percentages. The descriptive summary for the continuous variables will include number of subjects (n), means, medians, standard deviations, and minimum and maximum values. All data will be listed for all subjects.
This study is descriptive in nature, and no formal hypothesis testing will be performed. Any confidence intervals (CIs) generated will be 95%, unless stated otherwise.
All data will be listed for all subjects. All statistical analyses will be performed using SAS unless otherwise stated.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 8121 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [2] 8454 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [3] 9218 0
Rich River Health Group - Echuca
Recruitment hospital [4] 9219 0
Griffith University Clinical Trials Unit - Southport
Recruitment postcode(s) [1] 16178 0
4101 - South Brisbane
Recruitment postcode(s) [2] 16531 0
3220 - Geelong
Recruitment postcode(s) [3] 17874 0
3564 - Echuca
Recruitment postcode(s) [4] 17875 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 296439 0
Commercial sector/Industry
Name [1] 296439 0
Paradigm Biopharmaceuticals
Address [1] 296439 0
Level 2, 517 Flinders Lane
Melbourne
VIC 3000
Country [1] 296439 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Paradigm Biopharmaceuticals
Address
Level 2, 517 Flinders Lane
Melbourne
VIC 3000
Country
Australia
Secondary sponsor category [1] 295391 0
None
Name [1] 295391 0
Address [1] 295391 0
Country [1] 295391 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297670 0
Bellberry Human Research Ethics Committee B
Ethics committee address [1] 297670 0
129 Glen Osmond Road
Eastwood South Australia 5063
Ethics committee country [1] 297670 0
Australia
Date submitted for ethics approval [1] 297670 0
05/04/2017
Approval date [1] 297670 0
12/05/2017
Ethics approval number [1] 297670 0
2017-03-235

Summary
Brief summary
This will be a double blind randomised placebo controlled study in 24 subjects with Ross River virus induced arthralgia.

Rationale
PPS is a semi-synthetic heparin like macromolecular carbohydrate that resembles glycosaminoglycans. It has been widely used for its anti-inflammatory and regenerative properties in the treatment of interstitial cystitis. PPS also has fibrinolytic, lipolytic, and anticoagulant properties and is used for the treatment of thromboembolic prophylaxis in Europe. In Germany and Hungary, PPS is also approved in oral and injectable form for the treatment of peripheral arterial occlusive disease.

In a recent study in mice with Ross River virus induced joint disease, PPS administered for 10 days post infection significantly reduced the severity of joint symptoms, with reductions in joint swelling, inflammation in joints and muscle, and serum levels of mediators of inflammation which are implicated in the disease. PPS treatment also demonstrated a joint cartilage protective effect, with preservation of the thickness and structure of the joint cartilage.

On the basis of this research, Paradigm intends to evaluate the safety and efficacy of PPS treatment in human patients affected by joint symptoms following Ross River viral infection

The main inclusion criteria for the study will be:
1. Males and females aged 18 to 65 years (inclusive)
2. Confirmed diagnosis of Ross River virus infection based on laboratory definitive diagnosis
3. Clinical symptoms of Ross River virus infection including a minimum 2 joints involved
4. The onset of RRV infection symptoms minimum 12 weeks and maximum 36 weeks prior to Day 1

Treatment Intervention
Patients will be randomised 2;1 to receive either PPS or placebo respectively.
Dose schedule: 2 mg/kg administered by subcutaneous injection twice weekly for 6 weeks. Treatments will be given by medically qualified site staff, and patients will be evaluated and monitored at the regular visits during the study.

Objectives
The primary objective will be to evaluate the safety and tolerability of subcutaneous pentosan polysulfate sodium (PPS) in subjects with Ross River virus (RRV
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74758 0
Dr Paul Griffin
Address 74758 0
RIO Research unit, Mater Misericordiae Ltd
Level 3, Aubigny Place, Raymond Terrace
South Brisbane QLD 4101

Country 74758 0
Australia
Phone 74758 0
+61 402 077 302
Fax 74758 0
Email 74758 0
paul.griffin@mater.org.au
Contact person for public queries
Name 74759 0
Mrs Melanie Duiker
Address 74759 0
Project Manager
Paradigm BioPharmaceuticals
Level 2, 517 Flinders Lane, Melb, VIC, 3000, AUSTRALIA

Country 74759 0
Australia
Phone 74759 0
+61 478 694 464
Fax 74759 0
Email 74759 0
mduiker@paradigmbiopharma.com
Contact person for scientific queries
Name 74760 0
Dr Ravi Krishnan
Address 74760 0
Paradigm biopharmaceuticals
Level 2, 517 Flinders Lane
Melbourne
VIC 3000
Country 74760 0
Australia
Phone 74760 0
+61 412 095 125
Fax 74760 0
Email 74760 0
rkrishnan@paradigmbiopharma.com