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Trial registered on ANZCTR

Registration number

ACTRN12617000893303

Ethics application status

Approved

Date submitted

14/06/2017

Date registered

19/06/2017

Date last updated

18/06/2021

Date data sharing statement initially provided

8/04/2019

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]

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

Condition category

Condition code

Musculoskeletal

Other muscular and skeletal disorders

Inflammatory and Immune System

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]

Treatment: Drugs

Comparator / control treatment

Placebo control 0.9% NaCl for injection

Control group

Placebo

Outcomes

Primary outcome [1]

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]

Day 1 of Treatment to end of study (day 81)

Primary outcome [2]

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]

Day 1, 15, 29, 39 and 81

Primary outcome [3]

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]

Day 1, 39 and 81

Secondary outcome [1]

Change from baseline in patient assessed Quality of Life scores as assessed by SF-36 scores

Timepoint [1]

Day 1, 15, 29, 39 and 81

Secondary outcome [2]

Change from baseline in RAPID 3 scores (self assessed patient questionnaire to assess joint symptoms)

Timepoint [2]

Day 1, 15, 29, 39 and 81

Secondary outcome [3]

Change from baseline in pain intensity score as assessed by the Numeric Rating Scale (NRS) for pain

Timepoint [3]

Day 1, 15, 29, 39 and 81

Secondary outcome [4]

Changes in Coagulation (measured by APTT and INR)
(Primary outcome)

Timepoint [4]

Day 1, 15, 29, 39, 81

Eligibility

Key inclusion criteria

1. Males and females aged 18 - 65 years (inclusive)
2. Diagnosis of Ross River virus infection based on laboratory definitive or laboratory suggestive diagnosis according to Australian Government Ross River virus case definition
3. Current Ross River virus symptoms including a minimum of 2 joints involved (swollen and/or tender joint on examination)
4. Medically documented onset of RRV infection symptoms minimum 12 weeks and maximum 52 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

Sex

Both males and females

Can healthy volunteers participate?

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 any current or recent medication specified as per Prohibited Medications for this study.
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. Evidence of any active or clinically significant chronic condition including autoimmune disease involving the musculoskeletal system
8. Current evidence or recent history of other arthrogenic virus infection
9. Blood or plasma donation of more than 500 mL during the 3 months prior to Day 1
10. Currently hospitalised or any planned hospitalisations during the study period
11. 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
12. Currently active or recent history (within previous 12 months) of a gastric or duodenal ulcer, or suspicion of alimentary tract bleeding
13. History of significant hypersensitivity to PPS or drugs of a similar chemical or pharmacological class, including a history of heparin induced thrombocytopenia
14. Females who are breast feeding, pregnant or planning to become pregnant during participation in the study
15. Major surgery within 3 months prior to Day 1 or anticipated surgery in the study period
16. 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

Completed

Date of first participant enrolment

Anticipated

20/07/2017

Actual

7/08/2017

Date of last participant enrolment

Anticipated

1/06/2018

Actual

13/08/2018

Date of last data collection

Anticipated

20/11/2018

Actual

5/11/2018

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,VIC

Recruitment hospital [1]

Mater Adult Hospital - South Brisbane

Recruitment hospital [2]

Barwon Health - Geelong Hospital campus - Geelong

Recruitment hospital [3]

Rich River Health Group - Echuca

Recruitment hospital [4]

Griffith University Clinical Trials Unit - Southport

Recruitment hospital [5]

Sunshine Coast Clinical Research - Noosa Heads

Recruitment postcode(s) [1]

4101 - South Brisbane

Recruitment postcode(s) [2]

3220 - Geelong

Recruitment postcode(s) [3]

3564 - Echuca

Recruitment postcode(s) [4]

4215 - Southport

Recruitment postcode(s) [5]

4567 - Noosa Heads

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Paradigm Biopharmaceuticals

Address [1]

Level 2, 517 Flinders Lane
Melbourne
VIC 3000

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee B

Ethics committee address [1]

129 Glen Osmond Road 
Eastwood South Australia 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/04/2017

Approval date [1]

12/05/2017

Ethics approval number [1]

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.	Diagnosis of Ross River virus infection based on laboratory definitive or laboratory suggestive diagnosis 
3.	Current Ross River virus symptoms including a minimum 2 joints involved 
4.	The onset of RRV infection symptoms minimum 12 weeks and maximum 52 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

Dr Paul Griffin

Address

RIO Research unit, Mater Misericordiae Ltd
Level 3, Aubigny Place, Raymond Terrace
South Brisbane QLD 4101

Country

Australia

Phone

+61 402 077 302

Fax

paul.griffin@mater.org.au

Contact person for public queries

Name

Melanie Duiker

Address

Project Manager
Paradigm BioPharmaceuticals
Level 2, 517 Flinders Lane, Melb, VIC, 3000, AUSTRALIA

Country

Australia

Phone

+61 492922860

Fax

info@paradigmbiopharma.com

Contact person for scientific queries

Name

Ravi Krishnan

Address

Paradigm biopharmaceuticals
Level 2, 517 Flinders Lane
Melbourne
VIC 3000

Country

Australia

Phone

+61 492922860

Fax

info@paradigmbiopharma.com

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 Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study.	2021	https://dx.doi.org/10.1186/s12891-021-04123-w

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically