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Trial registered on ANZCTR


Registration number
ACTRN12617001437358
Ethics application status
Approved
Date submitted
6/10/2017
Date registered
11/10/2017
Date last updated
4/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Safety Study of BTX 1204 Solution in Patients with Atopic Dermatitis
Scientific title
A Randomised, Double-Blind, Vehicle-Controlled Study of the
Safety and Tolerability of BTX 1204 in Patients with Mild to
Moderate Atopic Dermatitis
Secondary ID [1] 292914 0
BTX.2017.004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atopic Dermatitis 304775 0
Condition category
Condition code
Skin 304089 304089 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 36 participants with atopic dermatitis will be enrolled and will receive BTX 1204 4% Solution or Vehicle Solution applied topically on their target lesion twice daily for 28 days. The Vehicle Solution will be identical to the BTX 1204 4% Solution, but without the active ingredient.
At the Day 1 Visit, participants will receive their first study drug application at the clinical site during the morning visit. Participants will be trained in the correct application of the study drug and provided an ample supply of study drug to complete twice daily dosing through Day 7. The first application of study drug will occur in the morning and the second application approximately 12 hours later. A diary will be maintained documenting compliance with the self-administered application.
At the Day 8 Visit, the participant will be provided an ample supply of study drug to complete dosing through Day 14. At the Day 15 Visit, the participant will be provided an ample supply of study drug to complete dosing through Day 28. The final application of study drug will be applied by the participant on the evening prior to the Day 29 Visit.
Intervention code [1] 299146 0
Treatment: Drugs
Comparator / control treatment
Approximately 36 participants will be randomised 2:1 to receive either active BTX 1204 4% Solution or Vehicle Solution. The Vehicle Solution will be identical to the BTX 1204 4% Solution, but without the active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 303407 0
The primary outcome for the study is to determine the safety and tolerability of BTX 1204 4% Solution with 28 days of twice daily application in participants with mild to moderate Atopic Dermatitis.

The primary outcome is assessed by: Adverse events, concomitant medications, laboratory findings (complete blood count, chemistry and urinalysis). Urine drug tests will be conducted for the presence of tetrahydrocannabinol. Signs of Atopic Dermatitis, cutaneous tolerability, patient reports of burning/stinging and pruritus will be recorded.
Timepoint [1] 303407 0
Timepoint:
Adverse events and concomitant medications monitored from time of consent through the Day 29 visit.
Complete blood count, chemistry, and urinalysis conducted at Baseline and at Day 29.
Urine drug tests for tetrahydrocannabinol (THC) levels conducted at the Baseline (Day 1), Day 8, Day 15, and Day 29 Visits.
Signs of atopic dermatis on the target lesion (erythema, exudation, excoriation, induration/papulation, and lichenification) will be obtained at the Baseline (Day 1), Day 8, Day 15, and Day 29 Visits.
Cutaneous tolerability (erythema, scaling, dryness, burning/stinging, and irritant/allergic contact dermatitis) will be obtained at the Baseline (Day 1), Day 8, Day 15, and Day 29 and graded using the following scale: 0, None; 1, Slight; 2, Moderate; 3, Severe.
Participant reports of burning/stinging and pruritus obtained daily on a Patient Diary.
Blood levels of study drug will be measured pre-dose on Day 1 (Baseline) and on Day 29.
Pregnancy testing will be conducted for women of child-bearing potential (WOCBP) at the Screening Visit, the Day 1 visit (if > 7 days from the Screening Visit), and at the Day 29 Visit.
Secondary outcome [1] 338853 0
Investigator’s Static Global Assessment on the target lesion will be obtained by the treating dermatologist(s)
Timepoint [1] 338853 0
Day 1 and Day 29 Visits.

Eligibility
Key inclusion criteria
To be included in the study, participants must meet the following inclusion criteria.
1. Participant (or legal guardian) has the ability and willingness to sign a written informed consent.
2. Participant is of either gender between 18 and 65 years of age, inclusive.
3. Participant is in good general health without clinically significant haematological, cardiac, respiratory, renal, endocrine, gastrointestinal, psychiatric, hepatic, or malignant disease, as determined by the investigator.
4. Participant has suitable venous access for blood sampling.
5. Participant is able and willing to complete the study and to comply with all study instructions and attend the necessary visits.
6. Participant has a diagnosis of atopic dermatitis according to Hanifin and Rajka [Hannifin 1980] as it relates to adult truncal or extremity atopic dermatitis, with:
a. At least one lesion 25 to 200 cm^2 in surface area (target lesion)
b. Target lesion on the trunk, upper extremities or lower extremities
c. Target lesion with a Signs of AD score of >= 6 and <= 12
7. Participant has an Investigator’s Static Global Assessment (ISGA) score on the target lesion of mild (2) or moderate (3).
8. Participant agrees to not use marijuana products throughout the study.
9. Male participants and their partners must agree and commit to use a barrier method of contraception.
10. A negative urine pregnancy test (UPT) result for all WOCBP at the Screening Visit and Baseline Visit. A WOCBP is one who is not permanently sterilised or not postmenopausal. Postmenopausal is defined as 12 months with no menses without an alternative medical cause.
11. Sexually active women must agree to use:
a. One of these highly effective contraception methods: Intrauterine device (IUD); hormonal (injections, implants, transdermal patch, vaginal ring); tubal ligation; partner vasectomy, OR
b. Oral contraceptives WITH a barrier method (Male or female condom; diaphragm; cervical cap; contraceptive sponge), OR
c. Two barrier forms of contraception (Male or female condom; diaphragm; cervical cap; contraceptive sponge)
12. Males participants must refrain from sperm donation during the study treatment period and until 90 days post study drug administration.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
If a participant meets any of the following exclusion criteria, they may not participate in the study.
1. Female participant who is breast feeding, pregnant, or planning to become pregnant.
2. Participant with history of known or suspected intolerance to the drug product excipients (hexamethyldisiloxane and polypropylene glycol (PPG) 15 stearyl ether).
3. Participant has used any marijuana products, via any route, within 4 weeks prior to the Screening Visit. A urine drug test positive for tetrahydrocannabinol (THC) will exclude the participant.
4. Participant has any significant active infection.
5. Participant has known HIV infection.
6. Participant has atopic dermatitis total body surface area involvement of >35%, excluding involvement of the face, scalp, and groin.
7. Participant has excessive body hair that would interfere with the evaluation of safety or with the diagnosis or assessment of AD.
8. Participant has sunburns, unevenness in skin tones, tattoos, scars, excessive hair, freckles, birthmarks, moles, or other skin damage or abnormality that would result in the inability to evaluate the target lesion.
9. Participant has unstable AD consistent with a requirement for high-potency corticosteroids.
10. Participant has an active or potentially recurring skin conditions(s) other than AD.
11. Participant has active impetigo at target lesion.
12. Participant has clinically significant or severe allergies.
13. Participant has used a topical immunomodulator (e.g., pimecrolimus or tacrolimus) within 14 days of the Screening Visit.
14. Participant has used topical corticosteroids to treat atopic dermatitis within 14 days of the Screening Visit.
15. Participant has used topical antibiotics to treat atopic dermatitis lesions within 14 days of Screening Visit.
16. Participant has used systemic or other immunosuppressive medications within 30 days of the Screening Visit (inhaled corticosteroid <= 1000 µg daily dose is acceptable).
17. Participant has used phototherapy within the past 14 days.
18. Participant has an underlying disease that requires the use of interfering topical or systemic therapy.
19. Participant has other dermatological conditions that require the use of interfering topical or systemic therapy or that might interfere with study assessments such as, but not limited to, acne or rosacea.
20. Participant has a clinically relevant history or currently suffering from any disease or condition that, in the opinion of the investigator, may affect the evaluation of the study product or place the participant at undue risk. This may include respiratory (including chronic asthma requiring repetitive drug interventions), gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, or connective tissue diseases or disorders.
21. Participant has a clinically relevant history of or current evidence of abuse of alcohol or other drugs. If the urine drug screen at the Screening Visit is positive for THC, the participant is not eligible to participate.
22. Participant is currently using any medication that, in the opinion of the investigator, may affect the evaluation of the study product or place the participant at undue risk.
23. Participant has participated in another investigational drug or device research study within 30 days of the Screening Visit or five half-lives of the drug, whichever is longer.
24. Any other reason that would make the participant, in the opinion of the investigator or sponsor, unsuitable for the 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)
Allocation is concealed and central randomisation will occur. A randomisation code will be prepared by an unblinded statistician. This statistician will be the only person aware of the randomisation code. Randomisation will be 2:1 (24 active:12 vehicle) and done by site. Once a participant is deemed eligible to enroll, randomisation will occur. The site will contact the Interactive Web-based Response System to receive the kit number to be used for that participant throughout the study.
Sealed, unblinding envelopes will be maintained at the investigators’ site only for circumstances where the clinical research organisation or sponsor cannot be contacted and the participant is in imminent danger without knowledge of their treatment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
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 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The selected sample size is based on having appropriate sensitivity to observe a safety signal. Thirty-six (36) participants, 24 receiving active BTX 1204 4% (w/w) Solution and 12 receiving Vehicle Solution, will be adequate to detect if there are any systemic safety or tolerability concerns.
All statistical processing will be performed using Statistical Analysis Software (SAS®) unless otherwise stated.
Safety Analyses: All participants who receive at least one confirmed dose of study drug, and have at least one post-Baseline assessment will be included in the safety analyses.
All treatment-emergent adverse events (TEAEs) occurring during the study will be recorded and classified based on MedDRA terminology. Treatment-emergent adverse events are those AEs with an onset on or after the first application of study medication. All reported TEAEs will be summarised by treatment group, the number of participants reporting events, system organ class, preferred term, severity, relationship to study drug, and seriousness.
Serious adverse events (SAEs) will be summarised by cohort, system organ class, preferred term, severity, outcome and relationship to study drug; and all SAEs will be listed by participant. In addition, a list of participants who discontinue from the study for any reason and the reason for discontinuation will be provided. The mean, standard deviation, median and range will be calculated for the change from Baseline in each Sign of AD (erythema, exudation, excoriation, induration/papulation, and lichenification) at each timepoint (Day 8, Day 15, and Day 29). In addition, a total score will be calculated based on the sum of each of the Signs of AD times the score (0, 1, 2, or 3; max score of 15) and the change from Baseline will be summarised for each timepoint.
Cutaneous tolerability scores for each parameter (erythema, scaling, dryness, burning/stinging, and irritant/allergic contact dermatitis) will be summarised for each visit. In addition, the change from Baseline in the mean scores will be summarised for each visit.
Summaries of the amount of burning/stinging and pruritus reported by the participants in the daily Patient Diary will be summarised using daily means by treatment. Graphic presentations will be prepared to display the changes in burning/stinging and pruritus over time.
Changes in laboratory parameters from Baseline to Day 29 will be summarised using shift tables to evaluate for trends. Abnormal laboratory findings will be summarised and listed by participant. Concomitant medications will be mapped to ATC Level 2 using the WHODrug dictionary. The number and percentage of participants reporting each medication will be summarised. Medications taken by each participant will be listed.
Drug Levels: Blood levels of study drug will be summarised for Baseline and Day 29. The mean, standard deviation (SD), median and range will be presented.
Demographics: Demographics/Baseline characteristics will be summarised by age, gender, race, ethnicity, height, weight, target lesion size, and BSA of AD.
ISGA: The change from Baseline for ISGA on the target lesion will be assessed on Day 29. The mean, SD, median, and range will be presented. The proportion of participants with an ISGA target lesion score of clear (0) or almost clear (1) and a decrease of 2-grades or more will be presented.
Target Lesion Size: The change from Baseline in the size of the target lesion will be determined.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
26/10/2017
Actual
17/11/2017
Date of last participant enrolment
Anticipated
28/02/2018
Actual
10/04/2018
Date of last data collection
Anticipated
30/03/2018
Actual
7/05/2018
Sample size
Target
36
Accrual to date
Final
37
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA,VIC
Recruitment hospital [1] 9142 0
Fremantle Dermatology - Fremantle
Recruitment hospital [2] 9143 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment hospital [3] 9144 0
Sinclair Dermatology - East Melbourne
Recruitment hospital [4] 9145 0
Veracity Clinical Research - Woolloongabba
Recruitment postcode(s) [1] 17534 0
3002 - East Melbourne
Recruitment postcode(s) [2] 17535 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 17533 0
5000 - Adelaide
Recruitment postcode(s) [4] 17529 0
6160 - Fremantle

Funding & Sponsors
Funding source category [1] 297544 0
Commercial sector/Industry
Name [1] 297544 0
Botanix Pharmaceuticals Ltd
Country [1] 297544 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Botanix Pharmaceuticals Ltd
Address
68 Aberdeen Street
Northbridge, Western Australia 6003
Country
Australia
Secondary sponsor category [1] 296554 0
None
Name [1] 296554 0
Address [1] 296554 0
Country [1] 296554 0
Other collaborator category [1] 279732 0
Commercial sector/Industry
Name [1] 279732 0
Novotech (Australia) Pty Limited
Address [1] 279732 0
Level 3, 235 Pyrmont St
Pyrmont, New South Wales, 2009
Country [1] 279732 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298639 0
Bellberry Limited
Ethics committee address [1] 298639 0
129 Glen Osmond Road
Eastwood, South Australia 5063
Ethics committee country [1] 298639 0
Australia
Date submitted for ethics approval [1] 298639 0
13/09/2017
Approval date [1] 298639 0
17/10/2017
Ethics approval number [1] 298639 0

Summary
Brief summary
The purpose of this study is to describe the safety and tolerability of the study drug compared to the vehicle solution with twice daily dosing in subjects with Atopic Dermatitis. Patients with Atopic Dermatitis aged between 18 and 65 years, inclusive, will participate.
BTX 1204 4% Solution or Vehicle Solution will be applied twice daily for 28 days.
The study consists of a screening visit (up to 14 days before receiving study treatment) and an enrolment visit initially. There is a visit on Day 8 and Day 15 during the 28 day dosing period. Participants will return to the clinic on Day 29 for safety assessments.
The maximum study duration for any participant will be a total of up to 43 days; screening period (up to 14 days), 28 days of treatment and a visit on Day 29.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77738 0
A/Prof Kurt Gebauer
Address 77738 0
Fremantle Dermatology
229 High Street
Fremantle, Western Australia 6160
Country 77738 0
Australia
Phone 77738 0
+61 8 9430 4488
Fax 77738 0
Email 77738 0
kurt@fremantledermatology.com.au
Contact person for public queries
Name 77739 0
Dr Michael Thurn
Address 77739 0
Chief Operating Officer
Botanix Pharmaceuticals Limited
68 Aberdeen Street, Northbridge WA 6003
Country 77739 0
Australia
Phone 77739 0
+61 2 6362 7663
Fax 77739 0
Email 77739 0
mthurn@botanixpharma.com
Contact person for scientific queries
Name 77740 0
Mr Mark Davis
Address 77740 0
Botanix Pharmaceuticals Limited
VP Clinical and Regulatory
610 W. Germantown Pike, Suite 400, Plymouth Meeting, PA 19462
Country 77740 0
United States of America
Phone 77740 0
+1 925 3361055
Fax 77740 0
Email 77740 0
mdavis@botanixpharma.com

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