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Trial registered on ANZCTR


Registration number
ACTRN12616001429448
Ethics application status
Approved
Date submitted
30/09/2016
Date registered
13/10/2016
Date last updated
26/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy and safety of a single injection of Articul One in comparison with Synvisc-One Registered Trademark or placebo for the treatment of symptomatic primary knee osteoarthritis.
Scientific title
A randomised, double-blind using blinded evaluator, placebo and active controlled, pilot study to evaluate the safety and efficacy of intra articular administration of Articul One in patient with symptomatic primary knee osteoarthritis
Secondary ID [1] 290004 0
MT-GPRT-KOA01
Universal Trial Number (UTN)
U1111-1187-3354
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis of the knee 300015 0
Condition category
Condition code
Musculoskeletal 299909 299909 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Product: Articul One
Dosage form: pre-filled syringe
Presentation: Blister containing 3mL syringe enclosed with rubber stoppers and 23G, 1" disposable needle, prefilled with 3mL of formulation as described below.
Route of Administration: Single Intra-articular injection
Formulation:
Ingredient 1: Sodium hyaluronate (60mg)
Ingredient 2: Sodium dihydrogen phosphate dehydrate (1.2mg)
Ingredient 3: Disodium hydrogen phosphate dehydrate (3.6mg)
Ingredient 4: Sodium Chloride (24.9mg)

Injection will be performed by qualified medical doctors who will be defined as Sub-Investigators in the study. The medical doctors in this study are specialists in pain management.
During the washout period (up to 21 days), participants will be asked to discontinue their anti-inflammatory agents (e.g., NSAIDs) and other analgesics prior to the Baseline Period.
Only paracetamol (not more than 4 grams per day) will be allowed as rescue medication and this cannot be used within 48 hours of any site visits.
Intervention code [1] 295712 0
Treatment: Drugs
Comparator / control treatment
Active comparator arm: Synvisc-One Registered Trademark (6ml) will be given as a single intra-articular injection.
Placebo: A 3mL intra-articular injection of Phosphate Buffered Saline.
Control group
Placebo

Outcomes
Primary outcome [1] 299394 0
WOMAC (Western Ontario and McMaster Universities Arthritis Index)
To assess the change from baseline in WOMAC A subscore*
Timepoint [1] 299394 0
At 12 weeks using Likert Scale in Articul One in patients with Knee Osteoarthritis.
Secondary outcome [1] 327040 0
WOMAC (Western Ontario and McMaster Universities Arthritis Index)
Change from Baseline in WOMAC A1 subscale
Timepoint [1] 327040 0
At weeks 4, 12, 20 and 26
Secondary outcome [2] 327041 0
WOMAC (Western Ontario and McMaster Universities Arthritis Index)
Change from Baseline in WOMAC A subscale
Timepoint [2] 327041 0
At weeks 4, 20 and 26
Secondary outcome [3] 327042 0
WOMAC (Western Ontario and McMaster Universities Arthritis Index)
Change from Baseline in WOMAC A subscale
Timepoint [3] 327042 0
Over 26 weeks
Secondary outcome [4] 327043 0
WOMAC (Western Ontario and McMaster Universities Arthritis Index)
Change from Baseline in WOMAC B subscale **
Timepoint [4] 327043 0
At weeks 4, 12, 20 and 26
Secondary outcome [5] 327044 0
Change from Baseline in WOMAC C subscale ***
Timepoint [5] 327044 0
At weeks 4, 12, 20 and 26
Secondary outcome [6] 327045 0
Clinician Observer Global Assessment (COGA) score
Timepoint [6] 327045 0
At weeks 4, 12, 20 and 26
Secondary outcome [7] 328312 0
Patient Global Assessment (PTGA) score
Timepoint [7] 328312 0
At weeks 4, 12, 20 and 26
Secondary outcome [8] 328314 0
Consumption of paracetamol
*: The WOMAC A subscale is calculated as a mean of 5 WOMAC A (pain) subscale.
**: WOMAC B subscale is calculated as a mean of WOMAC B (stiffness) subscale.
***: WOMAC C subscale is calculated as a mean of WOMAC C (Physical Function) subscale.
Timepoint [8] 328314 0
Over week 26

Eligibility
Key inclusion criteria
Provided written informed consent
Evidence of grade II or III OA (Kellergan-Lawrence scale) on X-ray
Has documented diagnosis of symptomatic primary osteoarthritis of the study knee made at least 3 months prior to Screening.
Has continued study knee osteoarthritis pain despite conservative treatment (e.g., weight reduction, physical therapy, analgesics).
Is ambulatory with an active lifestyle and in good general health.
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Had arthroplasty at the study knee at any time or any other previous surgery in the study knee within the 6 months prior to Screening, or planned surgery throughout the duration of the study.
History of septic arthritis in any joint.
Concomitant inflammatory disease or other condition that affects the joints.
Any known contraindication to paracetamol.

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)
At week 0, participants with symptomatic primary knee osteoarthritis will be randomized to receive a single intraarticular injection of Articul One or with Synvisc-One Registered Trademark or Placebo. Total 30 subjects (20 in Articul One, 5 in Synvisc-One Registered Trademark, 5 in Placebo) will be enrolled in the study.
Once a participant qualifies to participate in the study, the site will receive the randomization number for the participant via the interactive web response system (IWRS).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A block randomization method will be implemented using SAS ver.9 or higher. The entire randomization-related procedure will be performed and managed by IWRS
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
From previous studies that measured the WOMAC A change after Synvisc-One administration in patients with symptomatic primary knee osteoarthritis, the pre-dose to post-dose Week 12 score change was reported as 0.9+/-0.8 points, respectively(Chevalier). Therefore, this study assumed the expected for pre-dose to post-dose change in the WOMAC A score as 0.9 points, and the standard deviation for the change was assumed as 0.8 of standard deviations in prior studies.
Based on these assumptions and the significance level for a 2-sided test of 0.05, statistical power of 99%, the minimum sample size is calculated.
Considering drop-out rate of 25%, total 20 subjects were calculated.
In addition, this study is designed to exploratory comparison of the difference between Articul One vs Synvisc-One and Articul One vs Placebo. Thus total 10 subjects (5 in Synvisc-One, 5 in Placebo) additionally will be enrolled in the study.
The planned number of subjects is considered adequate to obtain data for effect size and sample size for subsequent next clinical studies.

For the efficacy assessment, the Full Analysis set is used as the main analysis set, and the Per Protocol set is also analyzed supportively and results are compared.

Recruitment
Recruitment status
Completed
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)
NSW
Recruitment postcode(s) [1] 14131 0
2292 - Broadmeadow

Funding & Sponsors
Funding source category [1] 294385 0
Commercial sector/Industry
Name [1] 294385 0
Medytox, Inc
Address [1] 294385 0
78 Gangni 1-gil
Ochang-eup , Cheongwon-gu
Cheongju-si, Chungcheongbuk-do
Country [1] 294385 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 4, 88 Jephson Street
Toowong, Brisbane, QLD 4066
Country
Australia
Secondary sponsor category [1] 293234 0
Commercial sector/Industry
Name [1] 293234 0
Medytox, Inc
Address [1] 293234 0
78 Gangni 1-gil
Ochang-eup , Cheongwon-gu
Cheongju-si, Chungcheongbuk-do
Country [1] 293234 0
Korea, Republic Of

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295808 0
Bellberry Ltd
Ethics committee address [1] 295808 0
129 Glen Osmond Rd, Eastwood, SA 5063
Ethics committee country [1] 295808 0
Australia
Date submitted for ethics approval [1] 295808 0
30/08/2016
Approval date [1] 295808 0
19/09/2016
Ethics approval number [1] 295808 0

Summary
Brief summary
This study aims to investigate the effectiveness and safety of a single intraarticular injection of Articul One in comparison with Synvisc-One Registered Trademark or placebo for the treatment of symptomatic primary knee osteoarthritis. 30 subjects will be randomized to receive either Articul one , the experimental arm (20 subjects), Synvisc-One Registered Trademark, the active comparator arm (5 subjects), or Placebo (5 subjects). This will be done by analysing questionnaires to understand the severity of the disease status, pain and rescue medication diary, and side effects. Safety will be monitored during the treatment visits using standard measures, including physical exams, vital signs (including oral temperature), and side effect monitoring.

Subjects may be eligible to join this study if they are aged over 40 years, have knee pain due to osteoarthritis of the knee and are in otherwise general good health.

This study will investigate a single dose of Articul One in comparison with Synvisc-One Registered Trademark or placebo (a treatment with no active ingredients which looks like the real thing but it is not). This study is ‘double-blind’ which means the subject and the assessing doctor, together with the study staff will not know whether the subject is receiving Articul One, Synvisc-One Registered Trademark or placebo. The person who administers the injection will be unblinded (they will know what treatment the subject will receive) however, they will not allow the subject or the assessing team know which treatment is being received.

The study includes a screening visit (visit 1) to check eligibility and to explain the study.. There will be 1 treatment visit (visit 2) which will occur within 21 days of visit 1. There will also be 4 further visits to assess the safety and effectiveness of the treatment. These visits will occur at weeks 4, 12, 20 and 26.

During the follow up period, four clinic visits are required for: review of diary, medications, AEs;. Participants will record rescue pain medication in a daily diary.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68506 0
Dr Marc Russo
Address 68506 0
Genesis Research Services Pty Limited
220 Denison Street
Broadmeadow NSW 2292

Country 68506 0
Australia
Phone 68506 0
+61 2 4985 1860
Fax 68506 0
Email 68506 0
PI@genesisresearchservices.com
Contact person for public queries
Name 68507 0
Mr Byungyun Han
Address 68507 0
Medytox, Inc
78 Gangni 1-gil
Ochang-eup , Cheongwon-gu
Cheongju-si, Chungcheongbuk-do
Country 68507 0
Korea, Republic Of
Phone 68507 0
+82.70.8666.6945
Fax 68507 0
+82.2.6941.2241
Email 68507 0
byungyun.han@medy-tox.co.kr
Contact person for scientific queries
Name 68508 0
Dr Wooshun Lee
Address 68508 0
Medytox, Inc
78 Gangni 1-gil
Ochang-eup , Cheongwon-gu
Cheongju-si, Chungcheongbuk-do
Country 68508 0
Korea, Republic Of
Phone 68508 0
+82.70.8666.6945
Fax 68508 0
Email 68508 0
drlee@medy-tox.co.kr

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary