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Trial registered on ANZCTR


Registration number
ACTRN12617001223325
Ethics application status
Approved
Date submitted
16/08/2017
Date registered
22/08/2017
Date last updated
7/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase II Trial of Safety, Tolerability and Efficacy Study of Topical AKP-11 Administration to Participants with Arthritis.
Scientific title
A Phase II, Randomized, Placebo-Controlled, Double Blind, Trial of Safety, Tolerability and Efficacy Study of Topical AKP-11 Administration to Participants with Arthritis.
Secondary ID [1] 292667 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
arthritis treatment 304409 0
osteoarthritis treatment 304410 0
rheumatoid arthritis treatment 304411 0
Gout treatment 304412 0
Condition category
Condition code
Musculoskeletal 303740 303740 0 0
Osteoarthritis
Inflammatory and Immune System 303775 303775 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
AKP-11 is a Sphingosine-1-phosphate receptor 1 (S1P1) agonist and 0.5 g of study gel will be topically applied 4 times a day (total daily application of 2 g).The study consists of 2 parts:
PART A investigates two doses of AKP-11 (daily dose 3% (60 mg) and 6% (120 mg) over 7 days in 20 participants (2 cohorts of 10 participants each) with osteoarthritis. Each cohort will have 8 participants on AKP-11 and 2 participants on placebo.
PART B will select the dose identified in PART A and will be conducted with treatment over 21 days in 80 participants with osteoarthritis, rheumatoid arthritis or gout. The dose of AKP-11 will be selected after the safety profile and efficacy of AKP-11 has been determined (dose selected will be in the range of 3 to 6%). The participants will be randomized to receive AKP-11 or Placebo in a ratio of 1:1.
PART A: 20 osteoarthritis participants
PART B: 80 arthritis participants
The participants will return all used and unused sachets to the study staff for accountability purposes.
Intervention code [1] 298904 0
Treatment: Drugs
Comparator / control treatment
A 0.5 g of placebo gel, containing ethanol, dimethyl sulfoxide, propylene glycol, water and hydroxyethyl cellulose, will be topically applied 4 times a day (total daily application of 2 g). 4 Participants will be treated with placebo for 7 days in Part A and 40 participants will be treated for 21 days in Part B.
Control group
Placebo

Outcomes
Primary outcome [1] 303109 0
Change in pain score from baseline, using 11-point numerical pain rating scale.
Timepoint [1] 303109 0
Days 1, 7 and 14 in Part A
Days 1, 7, 14, 21 and 28 in Part B
Secondary outcome [1] 337899 0
Change in swelling and tenderness scores from baseline, as a composite outcome. The joint swelling will be assessed on site visits using a 4-point severity scale, where 0 is no swelling and 3 is severe swelling. The joint tenderness will be assessed on site visits using a 4-point severity scale, where 0 is no pain and 3 is severe pain, when touched.
Timepoint [1] 337899 0
Days 1, 7, 14 in Part A
Days 1, 7, 14, 21 and 28 in Part B
Secondary outcome [2] 337900 0
Change in AUSCAN or WOMAC score. The AUSCAN questionnaire consists of 15 items of daily activity and will be completed by participants who have arthritis on their hands, as a treatment area. The WOMAC questionnaire consists of 17 questions and will be completed by participants who have arthritis on their knee, as a treatment area.
Timepoint [2] 337900 0
Days 1, 7 and 14 in Part A
Days 1, 7, 14, 21 and 28 in Part B
Secondary outcome [3] 337901 0
Patient Global Assessment response to treatment (PGART)
Timepoint [3] 337901 0
Days 3, 7 and 14 in Part A
Days 3, 7, 14, 21 and 28 in Part B

Eligibility
Key inclusion criteria
Males or females aged 18-75 years (inclusive) at the time of screening.
Primary complaint or clinical findings of osteoarthritis (PART A only).
Primary complaint or clinical findings of inflammatory arthritis (gout, osteoarthritis, rheumatoid arthritis) (PART B only).
Stable disease in both extent and severity for at least two weeks prior to the commencement of study treatment.
An average baseline pain score of equal or greater than 4 on a 11-point NRS (0 to 10) Scale over 3 days prior to randomization. All participants will need to score equal or greater than 4 on the 11 point NRS on Day 1
Baseline Swelling or Tenderness score of equal or greater than 1 prior to randomization.
Able to provide written informed consent prior to the performance of any study specific procedures.
BMI between 18.0 and 45.0 kg/m2, inclusive.
Female subjects of non-childbearing potential, defined as having a documented tubal ligation at least 6 weeks prior to dosing; having had a surgical bilateral oophorectomy (with or without hysterectomy); at least 12 months of spontaneous amenorrhoea with follicle stimulating hormone (FSH) greater than 40 MIU/ml.
Female participants of child-bearing potential with negative urine pregnancy test at screening and negative urine pregnancy test at check-in (Day 1), AND; Agree to abstinence for the duration of the study and until 4 weeks after dosing with study drug, if this is in line with the usual and preferred lifestyle; OR agree to use condoms plus one other acceptable form of contraception; i.e. intra-uterine device, hormonal contraception (oral, injected or implanted) or a female diaphragm, from screening until 4 weeks after dosing with study drug; OR has only same-sex partners; OR has a vasectomized partner, which should be the sole partner for that participant.
Male participants with female partners of child-bearing potential must agree to abstinence if this is in line with the usual lifestyle, or to use condoms plus partner use of an acceptable contraceptive (intrauterine device, hormonal contraception such as oral, injected or implanted; or male condom plus female diaphragm or cervical cap) for the duration of the study and until 4 weeks after dosing with study drug.
Negative test results for Human Immunodeficiency Virus (HIV), Hepatitis B and Hepatitis C at the time of screening.
Negative drug screening test (drugs of abuse; Creatinine control, testing for amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines) result (urine test) at the time of screening. In participants on prescribed opioids, a positive screening test for opioids is allowed
Participants who are willing and able to comply with all study assessments and adhere to the protocol schedule.

Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
History of allergy and/or hypersensitivity to any of the stated ingredients of the formulations. Current treatment with immunosuppressant agents or systemic corticosteroids.
Expected change in existing analgesia, and anti-inflammatory therapy.
Recent history of major joint injury or surgery.
Major chronic inflammatory disease (e.g Crohn’s disease, SLE) excluding rheumatoid arthritis,
Congenital or acquired immunodeficiency or cancer prone syndrome.
Have evidence of drug or alcohol abuse within 6 months prior to screening visits.
History of malignancy (other than adequately treated skin carcinoma or carcinoma-in-situ of the cervix).
Treatment with any of the following within 4 weeks prior to the commencement of study treatment and for the duration of the study: immunosuppressant agents (e.g. methotrexate, cyclosporine, azathioprine, thioguanine, prednisone, prednisolone, hydroxyurea or mycophenolate mofetil); biologics.
Topical treatment on the area to be studied within 2 weeks prior to commencement of study treatment and for the duration of the study, including: topical corticosteroids; topical NSAID or any other topical that in the opinion of the investigator could modify disease activity.
Have received any investigational research agent or therapeutic biologic within 30 days or 5 half-lives (whichever is longer) prior to the first dose of Investigational Product.
Have received an investigational vaccine within 6 months prior to baseline, or a live attenuated vaccine within 60 days prior to baseline, or intend to have a live vaccination during the course of the study (NB killed/inactive vaccines are allowed).
Have clinical signs of active infection and/or a temperature of greater than 38.0°C at the time of screening. Study entry may be deferred at the discretion of the Principal Investigator.
Anticipate surgery within the trial period or history of major surgery within 3 months of screening.
History of hypersensitivity to any other S1P receptor modulator.
A depot injection or an implant of any drug within 3 months prior to administration of study treatment, with the exception of a contraceptive implant.
Participants who are unable to return for all scheduled study visits.
Any clinically significant history or presence of neurological, endocrinal, cardiovascular, pulmonary, haematological, malignant, immunologic, psychiatric, metabolic or other uncontrolled systemic disease, with the exclusion of arthritis.
Any clinically significant abnormality at Screening determined by medical history, physical examination, blood chemistry, haematology, urinalysis and an 12-lead- ECG.
Any other condition that in the opinion of the investigator would render the subject unsuitable for enrolment, or could interfere with the subject participating in and completing the study or would put the participant at risk.



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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 297306 0
Commercial sector/Industry
Name [1] 297306 0
Akaal Pharma PTY LTD
Address [1] 297306 0
Akaal Pharma PTY LTD
Chemistry Department
Thomas Cherry Building # 301 E
La Trobe University
Bundoora, VIC - 3086
Country [1] 297306 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Akaal Pharma PTY LTD
Address
Akaal Pharma PTY LTD
Chemistry Department
Thomas Cherry Building # 301 E
La Trobe University
Bundoora, VIC - 3086
Country
Australia
Secondary sponsor category [1] 296276 0
None
Name [1] 296276 0
Address [1] 296276 0
Country [1] 296276 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298410 0
CALHN Research Ethics
Ethics committee address [1] 298410 0
CALHN Research Ethics
Royal Adelaide Hospital, North Terrace, Adelaide
South Australia 5000,
Ethics committee country [1] 298410 0
Australia
Date submitted for ethics approval [1] 298410 0
13/07/2017
Approval date [1] 298410 0
14/08/2017
Ethics approval number [1] 298410 0
HREC Reference No: HREC/17/RAH/249 R20170610

Summary
Brief summary
A primary purpose of this study is to evaluate Safety, Tolerability and Efficacy of Topical AKP-11 Administration to Participants with Arthritis. AKP-11 is a Sphingosine-1-phosphate receptor 1 (S1P1) agonist developed to treat multiple pathological events common in arthritis. The study consists of 2 parts: PART A investigates two doses of AKP-11 over 7 days in 20 participants (2 cohorts of 10 participants each) with arthritis. Each cohort will have 8 participants on AKP-11 and 2 participants on placebo. PART B will select the dose identified in PART A and will be conducted with treatment over 21 days in 80 participants with arthritis, The dose of AKP-11 will be selected after the safety profile and efficacy of AKP-11 has been determined. The participants will be randomized to receive AKP-11 or Placebo in a ratio of 1:1.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77002 0
Dr Richard Walsh
Address 77002 0
PARC Clinical Research (University of Adelaide),
Royal Adelaide Hospital, North Terrace, Adelaide
South Australia 5000,
Country 77002 0
Australia
Phone 77002 0
+61 8 8222 2712
Fax 77002 0
Email 77002 0
Walsh.Richard@sa.gov.au
Contact person for public queries
Name 77003 0
Dr Gurmit Gill
Address 77003 0
Akaal Pharma Pty Ltd
Chemistry Department
Thomas Cherry Building # 301 E
La Trobe University
Bundoora, VIC - 3086
Country 77003 0
Australia
Phone 77003 0
+61394792584
Fax 77003 0
Email 77003 0
Gurmit.Gill@latrobe.edu.au
Contact person for scientific queries
Name 77004 0
Dr Gurmit Gill
Address 77004 0
Akaal Pharma Pty Ltd
Chemistry Department
Thomas Cherry Building # 301 E
La Trobe University
Bundoora, VIC - 3086
Country 77004 0
Australia
Phone 77004 0
+61394792584
Fax 77004 0
Email 77004 0
Gurmit.Gill@latrobe.edu.au

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