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Trial registered on ANZCTR


Trial ID
ACTRN12616000009415
Ethics application status
Approved
Date submitted
18/12/2015
Date registered
12/01/2016
Date last updated
16/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Open label trial of intramuscular pentosan polysulfate on acute traumatic knee injury
Scientific title
A pilot study investigating the short-term outcome of intramuscular administration of pentosan polysulfate sodium for the treatment of bone marrow lesions of the knee
Secondary ID [1] 288109 0
PARA_001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bone marrow oedema lesion associated with acute traumatic knee injury 296974 0
Condition category
Condition code
Musculoskeletal 297232 297232 0 0
Other muscular and skeletal disorders
Injuries and Accidents 297395 297395 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single arm study -Twice weekly injections of pentosan polysulfate (PPS) for 3 weeks administered intra muscularly at a dose of 2 mg/kg.

PPS will be administered at the study site by clinical staff.
No specific strategies to monitor adherence are required.
Intervention code [1] 293417 0
Treatment: Drugs
Comparator / control treatment
No Control group

Changes from baseline
Control group
Uncontrolled

Outcomes
Primary outcome [1] 296818 0
Primary study objectives are to evaluate the safety and tolerability.
Specific assessments to evaluate safety and tolerability include the frequency and type of AEs, the use of concomitant medication for management of AEs, clinical laboratory testing (haematology, clinical chemistry, liver function tests, coagulation, urinalysis), physical examination and vital signs.

Particularly attention will be paid to the following types of AE:
-Injection site reactions
-Alopecia
-Abdominal pain, diarrhoea, nausea, dyspepsia, bleeding
-Headache
-Skin rashes
Timepoint [1] 296818 0
Day: 0, 4, 7, 11, 14, 18, 28, 42, 56

Day 0=first dose of study drug
Secondary outcome [1] 319466 0
Change in bone marrow lesions assessed by MRI
Timepoint [1] 319466 0
8 weeks post first injection
Secondary outcome [2] 319467 0
functional knee joint capacity assessed by Lysholm Knee score and Tegner Activity score
Timepoint [2] 319467 0
Day: 0, 4, 7, 11, 14, 18, 28, 42, 56

Day 0=first dose of study drug
Secondary outcome [3] 319635 0
Biomarkers- serum biomarkers of bone and collagen activity and inflammation
Timepoint [3] 319635 0
Day: 0, 7, 14, 28, 42, 56

Day 0=first dose of study drug
Secondary outcome [4] 319639 0
Pain assessed by Numeric Rating Scale NRS-11
Timepoint [4] 319639 0
Day: 0, 4, 7, 11, 14, 18, 28, 42, 56

Day 0=first dose of study drug

Eligibility
Key inclusion criteria
Subjects who have experienced an acute anterior cruciate ligament (ACL) injury a minimum of 1 week and maximum of 14 weeks prior to Day 0, and have been managed conservatively with physical therapy and medications
Subjects with bone marrow lesions of the femur or tibia on at least 2 consecutive sagittal or coronal MRI slices as confirmed by an independent reader.
OR
subjects who have experienced an acute anterior cruciate ligament (ACL) injury a minimum of 2 weeks maximum of 14 weeks prior to Day 0 and have been treated with surgical intervention to repair the acute injury within a minimum of 2 weeks and maximum of 14 weeks prior to Day 0.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects who have been treated with surgical intervention for the ACL injury in the affected knee
2. Subjects in whom surgery for the ACL injury in the affected knee is planned during the study period
3. Osteonecrosis, osseous infection/inflammation or visible cartilage damage of the affected joint
4. Systemic arthritis or osteoarthritis (OA) in multiple other joints

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not Applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not Applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Descriptive statistics no formal hypothesis testing

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)
SA,VIC
Recruitment hospital [1] 7499 0
Sportsmed SA Hospital - Stepney
Recruitment postcode(s) [1] 12470 0
5052 - Belair
Recruitment postcode(s) [2] 12471 0
3128 - Box Hill Central
Recruitment postcode(s) [3] 15325 0
5069 - Stepney

Funding & Sponsors
Funding source category [1] 292579 0
Commercial sector/Industry
Name [1] 292579 0
Paradigm BioPharmaceuticals Ltd
Address [1] 292579 0
Level 2,
517 Flinders Lane,
Melb, VIC, 3000, AUSTRALIA
Country [1] 292579 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Paradigm BioPharmaceuticals Ltd
Address
Level 2,
517 Flinders Lane,
Melb, VIC, 3000, AUSTRALIA
Country
Australia
Secondary sponsor category [1] 291301 0
None
Name [1] 291301 0
Address [1] 291301 0
Country [1] 291301 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294067 0
BELLBERRY HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 294067 0
129 Glen Osmond Rd
Eastwood SA 5063

Phone: 08 8361 3222
Fax: 08 8361 3322
Ethics committee country [1] 294067 0
Australia
Date submitted for ethics approval [1] 294067 0
14/10/2015
Approval date [1] 294067 0
20/11/2015
Ethics approval number [1] 294067 0
2015-10-686

Summary
Brief summary
The main aim of this study is to see whether pentosan polysulfate sodium (PPS) is safe and effective in treating Bone Marrow Oedema Lesion (BML) associated with acute knee injury and thereby relieving the pain caused by BML. Every person who participates in this study will receive a course of PPS injections.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62074 0
Prof Jegan Krishnan
Address 62074 0
Southern Adelaide Health Institute Inc.
13 Laffers Road,
Belair SA 5052
Country 62074 0
Australia
Phone 62074 0
618 82044279
Fax 62074 0
Email 62074 0
Jegan@Krishnan.com.au
Contact person for public queries
Name 62075 0
Mr Paul Rennie
Address 62075 0
Paradigm BioPharmaceuticals Ltd
Level 2,
517 Flinders Lane,
Melb, VIC, 3000,
AUSTRALIA
Country 62075 0
Australia
Phone 62075 0
+61 437 778 300
Fax 62075 0
Email 62075 0
prennie@paradigmbiopharma.com
Contact person for scientific queries
Name 62076 0
Dr Ravi Krishnan
Address 62076 0
Paradigm BioPharmaceuticals Ltd
Level 2,
517 Flinders Lane,
Melb, VIC, 3000,
AUSTRALIA
Country 62076 0
Australia
Phone 62076 0
+61412095125
Fax 62076 0
Email 62076 0
rkrishnan@paradigmbiopharma.com