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Trial registered on ANZCTR


Registration number
ACTRN12623000273684
Ethics application status
Approved
Date submitted
23/02/2023
Date registered
14/03/2023
Date last updated
16/06/2023
Date data sharing statement initially provided
14/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II Study to Investigate the Safety and efficacy of APC201 for the Treatment of Pain Associated with Osteoarthritis of the Knee
Scientific title
A Phase II Study to Investigate the Safety and efficacy of APC201 for the Treatment of Pain Associated with Osteoarthritis of the Knee
Secondary ID [1] 309076 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain associated with osteoarthritis of the knee 329137 0
Condition category
Condition code
Musculoskeletal 326113 326113 0 0
Osteoarthritis
Anaesthesiology 326114 326114 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Apply APC201 topically twice daily on affected knee(s) for 4 weeks. The intended dose of APC201 per administration is 3 actuations (0.75 mL x 3=2.25mL), equivalent to 94 mg of diclofenac sodium per knee for each administration. After screening, participants are randomly assigned to three treatment groups; Group 1 (Once a day arm of APC201) applied APC201 in the morning (AM) and Placebo at night (PM). Group 2 (Twice a day arm of APC201) applied APC201 in the AM and PM and Group 3 (Placebo arm) applied placebo in the AM and PM. A participant’s adherence to the assigned treatment plan will be assessed by reviewing entries on his/her diary card at each return visit.
Intervention code [1] 325516 0
Treatment: Drugs
Comparator / control treatment
Placebo: Lecithin (without API Diclofenac), topically once or twice daily on affected knee(s) for 4 weeks. After screening, participants are randomly assigned to three treatment groups, Group 1 through Group 3. Participants in Group 1 (Once a day arm of APC201) will apply APC201 as AM treatment and Placebo as PM treatment. Group 2 (Twice a day arm of APC201) will apply APC201 as both AM and PM treatments. Group 3 (Placebo arm) will apply the Placebo as both AM and PM treatments. Participants will bring diary card to each visit for site to check treatment compliance.
Control group
Placebo

Outcomes
Primary outcome [1] 333982 0
Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) LK3.1 Osteoarthritis (OA) Index – pain intensity in the target knee
Timepoint [1] 333982 0
Assessed at every study visit from Day 1 visit to End of study visit (Day 1 Randomisation visit, Days 8 and 29 visits post-commencement of intervention), change in McMaster Universities Index of Osteoarthritis (WOMAC) subscale scores for pain.
Secondary outcome [1] 418933 0
Change from baseline in WOMAC LK3.1 OA Index – physical function in the target knee
Timepoint [1] 418933 0
Assessed at every study visit from Day 1 visit to End of study visit (Day 1 Randomisation visit, Days 8 and 29 visits post-commencement of intervention), change in McMaster Universities Index of Osteoarthritis (WOMAC) subscale scores for physical function.
Secondary outcome [2] 418934 0
Change from baseline in WOMAC LK3.1 OA Index – stiffness in the target knee
Timepoint [2] 418934 0
Assessed at every study visit from Day 1 visit to End of study visit (Day 1 Randomisation visit, Days 8 and 29 visits post-commencement of intervention), change in McMaster Universities Index of Osteoarthritis (WOMAC) subscale scores for stiffness.
Secondary outcome [3] 418935 0
Change from baseline in Patient Global Assessment (PGA)
Timepoint [3] 418935 0
Assessed at Day 1 Randomisation visit, Days 8 and 29 visits post-commencement of intervention.
Secondary outcome [4] 418936 0
Pain intensity (11-point numerical rating scale)
Timepoint [4] 418936 0
Assessed at Day 1 Randomisation visit, Days 8 and 29 visits post-commencement of intervention.
Secondary outcome [5] 418937 0
To evaluate the safety of APC201 in osteoarthritis (OA) patients. Assessed by: incidence of Adverse Events graded using Common Terminology Criteria for Adverse Events (CTCAE 5.0). The possible adverse events are site application erythema and dryness.
Timepoint [5] 418937 0
Assessed daily for 4 weeks, from Visit 2 (Day 1), Visit 3 (Day 8) to Visit 4 (Day 29) post-commencement of intervention.
Secondary outcome [6] 418938 0
Skin irritation assessment, skin irritation will be assessed using an ordinal scale (0-4 where 0 represented no visible reaction and 4 represented erythema with induration and bullae)
Timepoint [6] 418938 0
Assessed daily for 4 weeks, from Visit 2 (Day 1), Visit 3 (Day 8) to Visit 4 (Day 29) post-commencement of intervention.
Secondary outcome [7] 418939 0
Use of rescue medication. The time of first use and number of rescue medication tablets used per day will be documented by participants on the diary card, reviewed carefully by the investigator at each study visit and reconciled for rescue medication accountability.
Timepoint [7] 418939 0
Assessed daily for 4 weeks, from Visit 2 (Day 1), Visit 3 (Day 8) to Visit 4 (Day 29) post-commencement of intervention.

Eligibility
Key inclusion criteria
1. Male or female Adult, 35 to 85 years of age, inclusive at the time of screening.
2. If female of childbearing potential, subject must be not pregnant as assessed by a pregnancy test at screening and agree to use an acceptable method of contraception (progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide) from enrolment up to 30 days after the study end. Female subject being postmenopausal for at least 1 year or surgically sterile is considered to be of no childbearing potential.
3. The subject is diagnosed with osteoarthritis of the knee for at least 3 months, according to the American College of Rheumatology (ACR) clinical and X-ray criteria.
4. X-ray of target knee(s) showing osteoarthritis of Kellgren-Lawrence grade 2 or above within 90 days of screening. If greater than 90 days an X-Ray will be required at time of screening period.
5. WOMAC pain sub-score (5 questions) higher than or equal to 8 and lower than or equal to 18 in the target knee, at the time of screening and at Baseline.
6. Knee pain in the target knee for 14 days of the preceding month (knee pain due to osteoarthritis and not due to another condition such as bursitis, tendinitis, etc.) at screening based on subject report.
7. On stable pain therapy (i.e., at least 3 days per week for the previous month) with an oral NSAID prescribed by physician and/or over-the-counter for 30 days prior to the start of screening.
8. Except for osteoarthritis, in reasonably good health as assessed by the Investigator.
9. Subject is able to provide written informed consent.
10. Subject agrees to maintain the usual level of activity throughout the course of the study.
11. Subject must agree to not showering, swimming or wetting the treated knee(s) within 2 hours of application.
12. Subject must agree to avoid exposing the treated knee(s) to natural or artificial sunlight.
13. The subject has a body mass index (BMI) is greater than or equal to 18.5 and less than 40.
Minimum age
35 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known or suspected hypersensitivity to NSAIDs (non-steroidal anti-inflammatory drugs), any of the components in either of the investigation products, or any physical impediment to apply IP on the target knee.
2. Known presence of gastrointestinal ulcer or any gastrointestinal bleeding within 6 months prior to Day 1.
3. Injection of corticosteroids or hyaluronic acid in the target knee within 6 months of Day 1 or into any other joint within 30 days of Day 1.
4. High dose oral/injected corticosteroid (more than 30 mg prednisone equivalent a day) treatment of more than 14 days during the past 6 months prior to Day 1.
5. Major surgery or arthroscopy of the target knee within one year prior to Day 1.
6. History of knee replacement.
7. Planned surgery of the target knee within 3 months of the screening visit.
8. Presence of an additional non-osteoarthritic disease affecting either knee, such as reactive arthritis, crystalline arthritis, ankylosing spondylitis, fibromyalgia, rheumatoid arthritis, psoriasis, gout or pseudo-gout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug.
9. Medical history of coronary artery bypass graft surgery.
10. Current cancer or treatment for cancer within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area.
11. Secondary osteoarthritis of the target knee, previous procedures or trauma affecting joint of the target knee.
12. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in hip(s) exceeds that of the target knee, presence of significant back pain, or at least one migraine attack within the past 12 months before Day 1, as reported by the subject.
13. Generalized skin irritation, previous skin reactions upon use of topical NSAIDs, current skin irritation or redness at the planned site of application, or significant skin disease including psoriasis, as judged by the investigator.
14. Prior stable therapy (more than 3 days a week for the month prior to Day 1) with an opioid analgesic or use of an opioid analgesic with 7 days prior to Day 1.
15. Use of duloxetine, pregabalin, or gabapentin within 30 days prior to Day 1.
16. History of alcohol or drug abuse within the past year prior to Day 1.
17. Donation or significant loss of blood (480 mL or more) within 60 days prior to Day1.
18. Administration of other investigational drugs within 30 days prior to Day 1.
20. Smoked or used nicotine-containing products within 6 months prior to Day 1.
21. Subject is not likely to complete the study for any reason as judged by the investigator.
22. Abnormal hepatic, renal or hematologic findings at screening:
The value of Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is greater than or equal to 2.5 times upper limit of normal;
The value of Total bilirubin is greater than or equal to 1.5 times upper limit of normal;
The value of Serum creatinine is greater than or equal to 1.5 times upper limit of normal;
The value of Hemoglobin is less than or equal to lower limit of normal.
23. Has used cannabis or any CBD or THC-containing product within 30 days of the screening visit and during the study.
24. Subject plans to use any OTC cosmetic tanning lotions to the target knee while on study.

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)
Centralised Randomisation system using EDC IRT system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random allocation schedule generated by computer program
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical Analysis Set:
Per-protocol (PP) population: all study subjects who have taken at least one dose of study product and had no major protocol violation.
Intent-to-treat (ITT) population: all randomized study subjects who have taken at least one dose of study product.
Safety Population: all study patients who have taken at least one dose of the study medications.
Statistical Analyses:
In Phase II the primary endpoint is the change of pain scores from baseline to that at week 4 in the WOMAC pain sub-score in the target knee. The absolute values and the absolute change from baseline in the WOMAC pain sub-score will be summarized over time by treatment group. Least square mean estimates of change from baseline in WOMAC pain sub-score along with 95% confidence intervals (CI) will be presented at each time-point for each treatment group.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2023
Actual
Date of last participant enrolment
Anticipated
1/12/2023
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment outside Australia
Country [1] 25288 0
Taiwan, Province Of China
State/province [1] 25288 0

Funding & Sponsors
Funding source category [1] 313281 0
Commercial sector/Industry
Name [1] 313281 0
Andros Pharmaceuticals Pty Ltd
Country [1] 313281 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Andros Pharmaceuticals Pty Ltd
Address
Level 7, 330 Collins Street, Melbourne Victoria 3000
Country
Australia
Secondary sponsor category [1] 315019 0
None
Name [1] 315019 0
Address [1] 315019 0
Country [1] 315019 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312510 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 312510 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 312510 0
Australia
Date submitted for ethics approval [1] 312510 0
26/04/2023
Approval date [1] 312510 0
06/06/2023
Ethics approval number [1] 312510 0
2023-01-069

Summary
Brief summary
This is a phase 2, randomized, double blind, placebo controlled trial to evaluate the efficacy and safety of twice daily APC201, for 4 weeks in adults with osteoarthritic pain of the knee. This will be done by analysing pain score and skin check, knee pain and rescue medication diary, and side effects. Safety will be monitored during treatment visits using standard measures, including physical exams, vital signs, clinical laboratory tests and side effect monitoring. Skin at the application sites will be checked to see if there is any irritation or reactions present after applications.
The primary purpose of phase 2 study is to evaluate the clinical efficacy and safety of APC201 in reducing pain in patients with osteoarthritis of the knee compared with those on placebo.
Trial website
Trial related presentations / publications
Public notes
key exclusion criteria:
19. Administration of a COVID-19 vaccine within 30 days prior to Day 1.

Contacts
Principal investigator
Name 124918 0
Dr Dr Indika Preethimal Leelasena
Address 124918 0
UniSc Clinical Trials, Morayfield.
Level 1/19-31 Dickson Rd, Morayfield Qld 4506
Country 124918 0
Australia
Phone 124918 0
+61 481127484
Fax 124918 0
Email 124918 0
ileelasena@usc.edu.au
Contact person for public queries
Name 124919 0
Dr Ae-June Wang
Address 124919 0
Andros Pharmaceuticals Co., Ltd.
6F, No. 22, Sec. 2, Shengyi Rd., Zhubei City, Hsinchu County 30261, Taiwan
Country 124919 0
Taiwan, Province Of China
Phone 124919 0
+88636581866
Fax 124919 0
Email 124919 0
ajwang@andros.com.tw
Contact person for scientific queries
Name 124920 0
Miss Ya-Ying Lin
Address 124920 0
Andros Pharmaceuticals Co., Ltd.
6F, No. 22, Sec. 2, Shengyi Rd., Zhubei City, Hsinchu County 30261, Taiwan
Country 124920 0
Taiwan, Province Of China
Phone 124920 0
+88636581866
Fax 124920 0
Email 124920 0
yylin@andros.com.tw

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.