A phase 2b, randomised double blind placebo controlled multicentre study to evaluate the effects of pentosan polysulfate sodium on treating pain in subjects with osteoarthritis of the knee and subchondral bone marrow lesions
A phase 2b, randomised double blind placebo controlled multicentre study to evaluate the effects of pentosan polysulfate sodium on treating pain in subjects with osteoarthritis of the knee and subchondral bone marrow lesions
Paradigm Biopharmaceuticals Pty Ltd
126 participants
Oct 27, 2017
Interventional
Conditions
Summary
The investigational product pentosan polysulfate (PPS) has various effects which suggest it may be useful in osteoarthritis. Preclinical (laboratory and animal studies) and clinical (human) studies have supported its potential role in OA. PPS has been shown to:; 1.Inhibit the cartilage degrading enzymes which play a key role in OA progression 2 Have anti-inflammatory effects including blocking the effects of the pro-inflammatory cytokines which are involved in osteoarthritis 3. Have antithrombic, antifibrotic and antilipidaemic effects which may assist with improved blood circulation in the bone. In this trial, patients with Osteoarthritis of the knee and associated Bone marrow lesions, who meet the study inclusion criteria, will be treated with either PPS or placebo, in a ratio of 1:1 according to a computer generated randomisation. The treatment will be given in double-blinded fashion (so that neither the patient, nor the person administering the treatment and assessing responses will know which treatment the patient received) The treatment will be given by subcutaneous injection, twice weekly for 6 weeks. Patients will visit the clinic according the the study schedule for the duration of treatment and up until Day 81, for monitoring and assessment of treatment responses, safety and adverse events recording. Treatment responses will be measured by changes in symptom scores according to KOOS questionnaire and NRS pain score at various time-points, and evolution of MRI images before treatment and at day 53. Patients will be further followed up with a phone call and symptom questionnaire on day 109 and 165.
Eligibility
Inclusion Criteria7
- Subjects with a clinical diagnosis of osteoarthritis in one or both knees and a radiographic diagnosis of knee osteoarthritis showing a Kellgren-Lawrence score 2, 3 or 4
- Symptomatic pain for at least 6 months preceding screening
- Males and females aged 40 to 75 years inclusive, who are willing and able to comply with study requirements
- Subjects must be able to provide written informed consent
- Body Mass Index (BMI) of 18 to 35.0 kg/m2 inclusive
- Females of non child-bearing potential or females and males willing to comply with medically acceptable contraceptive requirements of the study
- Presence of subchondral bone marrow lesions of the distal femur or proximal tibia on sagittal or coronal MRI slices, confirmed by radiologist at screening
Exclusion Criteria15
- Documented or reported history of increased bleeding tendency or thrombocytopenia
- Current treatment with anticoagulants or anti platelet drugs according to Protocol requirements
- Current or prior use of medicines which are prohibited for the duration of the study according to the Prohibited medicines and withhold periods in the study Protocol,
- Currently active or recent history (within preceding 12 months) of a gastric or duodenal ulcer, or suspicion of GI tract bleeding
- History or evidence of, or positive test for HIV, hepatitis B or hepatitis C
- Major surgery within 2 months preceding Day 1 or anticipated surgery in the study period
- Medical history or evidence of any active or chronic condition including autoimmune disease involving musculoskeletal system
- Currently hospitalised or any planned hospitalisations during the study period
- Knee surgery or trauma within 6 months preceding Day 1
- Participation in another clinical trial or administration of any investigational product within 8 weeks or 5 half-lives (whichever is longer) preceding Day 1
- Contraindications to MRI scans
- History of significant allergy to PPS or similar drugs
- Any clinically significant abnormalities on clinical chemistry, haematology, urinalysis, physical examination, medical history, 12-lead ECG, or vital signs as judged by the investigator and/or sponsor (at Screening)
- 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 jeopardise the safety of the subject or the validity of the study results
- An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.
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Interventions
2mg/kg Pentosan Polysulfate Sodium (100mg/ml injectable solution), administered by subcutaneous injection, twice weekly for 6 weeks. Patients will visit the clinical trial centre twice weekly for 6 weeks for treatment injections, which will be given by experienced clinical trial nurses.
Locations(6)
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ACTRN12617001311347