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Trial registered on ANZCTR


Registration number
ACTRN12618001014246
Ethics application status
Approved
Date submitted
17/04/2018
Date registered
18/06/2018
Date last updated
18/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
This study looks into the effects of FDY-5301 in relation to skeletal muscle loss after full knee replacement.
Scientific title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Intravenous FDY-5301 in Tourniquet Induced Sarcopenia in knee-replacement patients
Secondary ID [1] 294569 0
FDY-5301-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Total Knee Arthroplasty (TKA) 307346 0
Sarcopenia 307724 0
Condition category
Condition code
Surgery 306452 306452 0 0
Other surgery
Musculoskeletal 306785 306785 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At least 30 evaluable patients will be enrolled to receive a single dose of 1.0 mg/kg FDY-5301 or placebo (n=15 per group) by bolus injection intra-operatively by the surgeon or medical team. Patients undergoing unilateral TKA with tourniquet use intra-operatively will receive either FDY-5301 or volume matched placebo after informed consent is obtained, provided the tourniquet has been inflated at least 45 minutes, within 5-10 minutes prior to tourniquet deflation and limb reperfusion. For each participant, the study will consist of screening, total knee arthroplasty (TKA) and study drug treatment on day 1, evaluations on day 2, and follow-up visits at 3 weeks and 6 weeks after receiving the study drug

All patients will have study outcomes monitored for 2 days and at 3 weeks and 6 weeks post operatively.
Subject to the results in this cohort of patients, a decision will be made to proceed with more patients or other doses in future cohorts, or not.
Intervention code [1] 300860 0
Treatment: Drugs
Comparator / control treatment
The placebo product is sterile normal saline containing no drug substance. Each 20 mL (fill volume) vial will be a clear solution and is formulated to contain 9 g/L of NaCl
Control group
Placebo

Outcomes
Primary outcome [1] 305464 0
The functional mobility assessment (standardized stair ascent and descent assessment) will compare the amount of time it takes for placebo vs. FDY-5301 treated patients to ascend and descend a set of stairs at 6 weeks post-TKA and will be expressed as change from baseline in stair ascent and descent times..
Timepoint [1] 305464 0
The functional mobility assessment (muscle strength by isometric extension and flexion and muscle function ) is performed only at screening and 6 weeks after surgery (TKA) due to the required healing time after TKA [primary timepoint]
Secondary outcome [1] 345329 0
Measure of additional functional mobility outcomes including TUG and 6 minutes walking distance
Timepoint [1] 345329 0
These measurements will be evaluated at screening and 6 week post- TKA only due to the healing from the TKA
Secondary outcome [2] 345330 0
This is a composite outcome of quadriceps and hamstring strength tests which is measured using a hand-held dynamometer and compared results between screening and 6 week post TKA.
Timepoint [2] 345330 0
Strength tests will be conducted at screening and 6 weeks post TKA
Secondary outcome [3] 345331 0
MRI evaluation (which is a composite outcome of quadriceps and other thigh muscle volume) - in both legs
Timepoint [3] 345331 0
MRI will be evaluated at screening and 3 and 6 weeks post -TKA
Secondary outcome [4] 346467 0
KOOS knee survey patient questionnaire will be used. The KOOS accesses pain, function, mobility and quality of life at the same time
Timepoint [4] 346467 0
The KOOS will be completed by the participant at screening and 3 and 6 weeks post- TKA
Secondary outcome [5] 347850 0
Explore biomarkers of FDY-5301 activity and muscle injury and inflammation from plasma and serum samples
Timepoint [5] 347850 0
Biomarkers are taken at screening, day 0 (treatment), day 1, 3 weeks and 6 weeks post TKA
Secondary outcome [6] 347964 0
Safety lab values composed outcome of clinical chemistry,. haematology and thyroid values to evaluate safety of treatment with serum assay
Timepoint [6] 347964 0
Safety evaluation is performed at screening, day 1, 3 and 6 weeks follow-up post TKA
Secondary outcome [7] 347965 0
Composite outcome of postoperative pain (evaluated with the KOOS questionnaire), time to first analgesic (hospital record), time to hospital discharge (hospital record), and the time it takes to return to normal function (hospital records) and quality of life (KOOS) will be compared between treatment groups.
Timepoint [7] 347965 0
These will be documented when applicable, either at screening and/or day 0, day 1, 3 and 6 weeks post TKA.

Eligibility
Key inclusion criteria
At least 30 patients
1. 60-85 year old male or female patients
2. Admitted for elective first total knee replacement surgery of one limb due to osteoarthritis.
3. Informed consent to study participation

Minimum age
60 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Anticipated tourniquet inflation for less than 45 minutes
2. Women of childbearing potential
3. Known contraindication to MRI (e.g. pacemaker)
4. Significant limb deformity as determined by the investigator, or prior lower limb osteotomy
5. Post traumatic or inflammatory arthritis of the operated limb
6. Patients with known thyroid disease, or known allergy to iodide
7. Patients with significant renal impairment (GFR<50)
8. Body weight > 120 kg or Body Mass Index (BMI) > 35 kg/m2
9. Use of investigational drugs or devices within 30 days prior to enrollment into the study
10. Life expectancy of less than 1 year
11. Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
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
The primary outcome for this study will be functional mobility assessed by timed stair ascent and descent compared between the FDY-5301 and placebo treated groups at 6 weeks post-TKA.
A total sample size of 30 patients, ie. 15 per group will provide 80% power to detect a statistically siginificant difference of 31.4% between groups in timed stair ascent and descent at 6 weeks expressed as percent change over baseline ( two-sided alpha=0.05%). Equal variance based on a standard deviation of 15.9% for each group was assumed. These metrics are based on published data.
Statistical evaluation of our data will be performed using separate analysis of covariance (ANOVA) models at 2 weeks and 6 weeks post-TKA, comparing the placebo vs. FDY-5301 treated groups in terms of change from baseline on anatomical, physiological and functional mobility measures. Differences between the means will be considered significant at P = 0.05. All values will be expressed as the mean (SE) or a percentage.
Multilevel models (MLM) will be used to determine correlations between muscle atrophy and other covariates with functional mobility within the context of nested non-independent responses such as change from baseline over time in each patient.
In addition to the measurement of safety and efficacy parameters in this study, soluble biomarker levels will also be assessed.

Recruitment
Recruitment status
Not yet 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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 10625 0
Emeritus Research - Camberwell
Recruitment hospital [2] 11115 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 22343 0
3124 - Camberwell
Recruitment postcode(s) [2] 22928 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 299186 0
Commercial sector/Industry
Name [1] 299186 0
Faraday Pharmaceuticals Australia PTY LTD
Address [1] 299186 0
C/- Deloitte Tax Services Pty Ltd,
Level 25 Riverside Centre, 123 Eagle Street
Brisbane QLD 4000, Australia
Country [1] 299186 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Faraday Pharmaceuticals Australia PTY LTD
Address
C/- Deloitte Tax Services Pty Ltd,
Level 25 Riverside Centre, 123 Eagle Street
Brisbane QLD 4000, Australia
Country
Australia
Secondary sponsor category [1] 298449 0
None
Name [1] 298449 0
Address [1] 298449 0
Country [1] 298449 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300110 0
Avenue Private Hospital
Ethics committee address [1] 300110 0
Australian Hospital Care (The Avenue) Pty Ltd trading as
The Avenue Hospital
ABN 12 072 759 338
40 The Avenue
Ethics committee country [1] 300110 0
Australia
Date submitted for ethics approval [1] 300110 0
31/01/2018
Approval date [1] 300110 0
09/04/2018
Ethics approval number [1] 300110 0
Ethics committee name [2] 300112 0
Bellberry Limited Commitee E
Ethics committee address [2] 300112 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [2] 300112 0
Australia
Date submitted for ethics approval [2] 300112 0
06/04/2018
Approval date [2] 300112 0
Ethics approval number [2] 300112 0
Ethics committee name [3] 300630 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [3] 300630 0
Ethics committee country [3] 300630 0
Australia
Date submitted for ethics approval [3] 300630 0
12/06/2018
Approval date [3] 300630 0
Ethics approval number [3] 300630 0

Summary
Brief summary
This is a phase 2, randomized, double-blind, placebo-controlled study of intravenous FDY-5301 in tourniquet induced sarcopenia in patients undergoing unilateral TKA.
Study patients will be recruited at each investigational site (or referred to the investigative site from another institution) for first unilateral TKA. Patients will be screened and written informed consent will be obtained prior to initiation of any study related procedures in those patients who meet the inclusion and exclusion criteria for the study.
A minimum of 30 evaluable patients will be enrolled and randomized to receive either FDY-5301 1.0mg/kg or volume-matched placebo.
Study drug administration will occur by bolus injection at any time between 10 and 5 minutes prior to tourniquet release/limb reperfusion.
All patients who receive study drug and have tourniquet use will be followed up for safety and efficacy for 6 weeks post-study drug administration.. Patients who do not undergo toirniquet inflation for any reason who received study drug will be followed up for safety, but will be replaced with a new patient.
Trial website
NA
Trial related presentations / publications
NA
Public notes
NA

Contacts
Principal investigator
Name 82602 0
Prof Stephen Hall
Address 82602 0
Emeritus Research Pty Ltd
Level 2, 1180 Toorak Road,
CAMBERWELL, VIC, 3124
Country 82602 0
Australia
Phone 82602 0
+61 3 9509 6166
Fax 82602 0
Email 82602 0
stephenhall@emeritusresearch.com
Contact person for public queries
Name 82603 0
Mrs Sandra Williams
Address 82603 0
Emeritus Research Pty Ltd
Level 2, 1180 Toorak Road,
CAMBERWELL, VIC, 3124
Country 82603 0
Australia
Phone 82603 0
+61 3 9509 6166
Fax 82603 0
Email 82603 0
SandraWilliams@emeritusresearch.com
Contact person for scientific queries
Name 82604 0
Mrs Emily VandenEkart
Address 82604 0
Faraday Pharmaceuticals, Inc.
1616 Eastlake Ave E, Suite 560
Seattle, WA 98102
Country 82604 0
United States of America
Phone 82604 0
+1 (206) 946-1989
Fax 82604 0
Email 82604 0
EVandenEkart@FaradayPharma.com

No data has been provided for results reporting
Summary results
Not applicable