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Trial registered on ANZCTR


Registration number
ACTRN12617000763347
Ethics application status
Approved
Date submitted
17/05/2017
Date registered
24/05/2017
Date last updated
14/01/2019
Date data sharing statement initially provided
14/01/2019
Date results information initially provided
14/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and efficacy of topical application of AK-11 to participants with atopic dermatitis
Scientific title
A Phase II, safety, tolerability and efficacy study of topical AKP-11 administration to participants with atopic dermatitis.
Secondary ID [1] 291969 0
CT-2017-CTN-01676-1 v1.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 303316 0
Condition category
Condition code
Skin 302756 302756 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The administration involves two times a day topical application of AKP-11 ointments to participants with atopic dermatitis (AD) for up to 28 days. The 1 g ointment contains 0 mg or 30 mg of active AKP-11 contained in a sachet which will be applied twice daily to an allocated atopic dermatitis area as determined by the investigator. Participants are allocated to receive 0 mg (placebo) or 30 mg of AKP-11. The allocated area will be equal or less than 3% of treatable body surface area. During each application, the entire content of the study ointment will be applied thinly on the allocated atopic dermatitis
area/s (~1.5mg/ cm2). After the study ointment has been applied in a uniform layer, the
area will be thoroughly rubbed for approximately one minute. The application site can be covered with clothes after study ointment application.
Intervention code [1] 298096 0
Treatment: Drugs
Comparator / control treatment
Placebo controlled treatment
Control group
Placebo

Outcomes
Primary outcome [1] 302144 0
Proportion of participants achieving success in Investigators Static Global Assessment (ISGA) as two grades or greater improvement from baseline.
Timepoint [1] 302144 0
Days 1, 8, 15, 22, 29 & 36
Primary outcome [2] 302185 0
Safety endpoints: Clinical signs and symptoms (Adverse events (AEs)) and Treatment Emergent Adverse Events (TEAEs; ). Any untoward medical occurrence in a participant or clinical investigation participant, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Examples of an AE include:
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency and/or intensity of the condition: New conditions detected or diagnosed after investigational product administration even though it may have been present prior to the start of the study: Signs, symptoms, or the clinical sequelae of a suspected interaction: Signs, symptoms, or the clinical sequelae of a suspected overdose of either investigational product or a concurrent medication (overdose per se should not be reported as an AE/SAE). The Investigator and designated study personnel will monitor each participant for AEs during the study. All AEs reported between consent and final follow-up will be recorded in the case report form (CRF). The investigator or designee will ask the participant non-leading questions in an effort to detect adverse events. Examples of this are: “How are you feeling?” Or
“Since you were last asked, have you felt unwell or different from usual?” In addition, participants should be encouraged to spontaneously report any unusual feelings or sensations.
Timepoint [2] 302185 0
Days 1, 8, 15, 22, 29, 36
Primary outcome [3] 302186 0
Safety endpoints; Physical examination and Vital signs (BP, temp, heart rate, respiratory rate)
Timepoint [3] 302186 0
Days 1, 15, 29, 36
Secondary outcome [1] 334960 0
Time to improvement in ISGA.
Timepoint [1] 334960 0
Days 1, 8, 15, 22, 29 & 36
Secondary outcome [2] 334961 0
Proportion of patients achieving improvement in pruritus signs (none (0) or mild (1) with greater than or equal to 1 grades improvement) from baseline. At the clinic, on Day 1, 8, 15, 22, 29 and 36 (EOS) participants will be asked “On average, over the past 24 hours, how itchy was the allocated atopic dermatitis area?” The severity of itch will be assessed with the use of the 4-point itch rating scale of none (0), mild (1), moderate (2) and severe (3).
Timepoint [2] 334961 0
Days 1, 8, 15, 22, 29 & 36
Secondary outcome [3] 334962 0
Time to improvement in pruritus. At the clinic, on Day 1, 8, 15, 22, 29 and 36 (EOS) participants will be asked “On average, over the past 24 hours, how itchy was the allocated atopic dermatitis area?” The severity of itch will be assessed with the use of the 4-point itch rating scale of none (0), mild (1), moderate (2) and severe (3).
Timepoint [3] 334962 0
Days 1, 8, 15, 22, 29 & 36
Secondary outcome [4] 335128 0
The skin irritation assessment will be used to assess an area of normal skin (i.e. without atopic dermatitis) that was also in contact with the study ointment to assess the irritability of the study IP. The skin irritation will be assessed by Severity of Erythema, using 5 point scale and Severity of Edema, using 4 point scale.
Timepoint [4] 335128 0
Days 8, 15, 22, 29 and 36

Eligibility
Key inclusion criteria
Males or females aged 18-65 years (inclusive) at the time of screening.
Individuals diagnosed with atopic dermatitis according to the American Academy of Dermatology diagnostic features and with stable atopic dermatitis in both extent and severity for at least two weeks prior to commencement of study treatment.
Individuals with mild to severe disease with less than or equal to 20% of body surface area (BSA; other than hair bearing scalp, palms of hands, soles and feet and genitals) with atopic dermatitis.
Baseline Investigator’s Static Global Assessment (ISGA) score of mild (2) to severe (4).
Participant is able to provide written informed consent prior to the performance of any study specific procedures.
Participants with a BMI between 18 and 45.0 kg/m2, inclusive.
Female subjects of non-childbearing potential, defined as (1) having a documented tubal ligation at least 6 weeks prior to dosing; (2) having had a surgical bilateral oophorectomy (with or without hysterectomy); (3) at least 12 months of spontaneous amenorrhoea with follicle stimulating hormone (FSH) > 40 MIU/ml.
Female participants of child-bearing potential with negative urine pregnancy test at screening and negative urine pregnancy test at 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.
A 12-lead ECG at screening that in the opinion of the investigator, has no abnormalities that compromise subject’s safety in this study.
Participants who are willing and able to comply with all study assessments and adhere to the protocol schedule.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants with any skin condition other than atopic dermatitis, in particular cutaneous infections, significant sun damage or an inherited skin disorder that in the opinion of the Investigator could interfere with the evaluation of the trial medication.
History of allergy and/ or hypersensitivity to any of the stated ingredients of the formulations.
Treatment with any of the following within 4 weeks prior to the commencement of study treatment and for the duration of the study: systemic retinoids; systemic immunosuppressant agents (e.g. methotrexate, cyclosporine, azathioprine, thioguanine prednisone, prednisolone, hydroxyurea or mycophenolate mofetil, biologics); phototherapy or photochemotherapy; “alternative medicine” treatments; or deliberate abnormal sun exposure or tanning bed use, or
any other therapy that in the opinion of the investigator could modify disease activity.
Topical treatment within 2 weeks prior to commencement of study treatment and for the duration of the study to the area to be treated with the study ointment, including: topical corticosteroids; topical calcineurin inhibitor or any other topical treatments 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 above 38.0 degrees 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.
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 sign consent or unable to return for all scheduled study visits.
Evidence of current or previous clinically significant neurological, endocrinal, cardiovascular, pulmonary, haematological, malignant, immunologic, psychiatric metabolic or other uncontrolled systemic disease, or finding of the medical examination (including vital signs and ECG), including any other condition that in the opinion of the investigator, would compromise the safety of the participant or interfere with assessment of endpoints or unsuitable for enrollment or impact on the quality of the data.

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
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Study terminated upon a request of a licensee, who will conduct phase II trials.
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] 296479 0
Commercial sector/Industry
Name [1] 296479 0
Akaal Pharma PTY LTD
Address [1] 296479 0
Akaal Pharma PTY LTD
Chemistry Department
Thomas Cherry Building # 301E
La Trobe University
Bundoora, VIC - 3083
Country [1] 296479 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Akaal Pharma PTY LTD
Address
Akaal Pharma PTY LTD
Chemistry Department
Thomas Cherry Building # 301E
La Trobe University
Bundoora, VIC - 3083
Country
Australia
Secondary sponsor category [1] 295437 0
None
Name [1] 295437 0
Address [1] 295437 0
Country [1] 295437 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297701 0
The Central Adelaide Local Health Network (CALHN) Research Ethics
Ethics committee address [1] 297701 0
CALHN Research Ethics Committee
North Terrace
Adelaide; SA 5000
Ethics committee country [1] 297701 0
Australia
Date submitted for ethics approval [1] 297701 0
Approval date [1] 297701 0
24/04/2017
Ethics approval number [1] 297701 0

Summary
Brief summary
The existing treatments to treat atopic dermatitis have limitations with side effects and long-term use. The medication called AKP-11, is an experimental topical formulation being investigated for its potential as a treatment for atopic dermatitis. The use of AKP-11 in this study is purely experimental. AKP-11 as ointment was applied to 10 psoriasis and 8 atopic dermatitis participants and no serious side effects were reported. The primary purpose of this study to to further determine a safety, tolerability and efficacy of topical doses of AKP-11 when administered to participants with atopic dermatitis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74878 0
Dr Richard Walsh
Address 74878 0
Ward S4A, Lvl 4, North Wing,
Royal Adelaide Hospital
North Terrace
Adelaide, SA 5000
Country 74878 0
Australia
Phone 74878 0
+618 8222 2712
Fax 74878 0
Email 74878 0
Richard.Walsh@sa.gov.au
Contact person for public queries
Name 74879 0
Dr Gurmit Gill
Address 74879 0
Akaal Pharma Pty Ltd
Chemistry Department
Thomas Cherry Building # 301E
La Trobe University
Bundoora, VIC - 3083
Country 74879 0
Australia
Phone 74879 0
+61394792584
Fax 74879 0
Email 74879 0
gurmit.gill@latrobe.edu.au
Contact person for scientific queries
Name 74880 0
Dr Gurmit Gill
Address 74880 0
Akaal Pharma Pty Ltd
Chemistry Department
Thomas Cherry Building # 301E
La Trobe University
Bundoora, VIC - 3083
Country 74880 0
Australia
Phone 74880 0
+61394792584
Fax 74880 0
Email 74880 0
gurmit.gill@latrobe.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
final study report will be prepared
What supporting documents are/will be available?
Study protocol
Ethical approval
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