None listed
Conditions
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
Interventions
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 week
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.
Sponsors
Paradigm Biopharmaceuticals
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
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
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
Outcome results
None listed