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Trial registered on ANZCTR


Registration number
ACTRN12621000689875
Ethics application status
Approved
Date submitted
8/04/2021
Date registered
7/06/2021
Date last updated
31/10/2022
Date data sharing statement initially provided
7/06/2021
Date results information initially provided
23/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Vehicle-Controlled Study of the Safety and Tolerability of BTX 1702 in Patients with Papulopustular Rosacea
Scientific title
A Randomised, Double-Blind, Vehicle-Controlled Study of the Safety and Tolerability of BTX 1702 in Patients with Papulopustular Rosacea
Secondary ID [1] 303416 0
BTX.1702.111
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Papulopustular Rosacea 320703 0
Condition category
Condition code
Skin 318548 318548 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BTX 1702 10% (w/w) Gel or BTX 1702 20% (w/w) Gel will be applied twice daily (BID) for 56 days.
All patients will have 1.5mL of study medication applied BID to the entire face. No escalation of dose will occur.
All patients will be required to maintain a daily dosing diary documenting each application of the study medication.
Patients will return the study medication bottles within the medication kit at each visit so that the unblinded study site staff can weigh study medication kits to ensure patient compliance with dosing.
Intervention code [1] 319723 0
Treatment: Drugs
Comparator / control treatment
BTX 1702 Vehicle Gel will be applied twice daily (BID) for 56 days following the same schedule as intervention participants.
Control group
Placebo

Outcomes
Primary outcome [1] 326512 0
Reported adverse events (AEs) including treatment-emergent adverse events (TEAE)
Timepoint [1] 326512 0
Baseline to Days 15, 29 (pre and post dose), and post intervention at EOS Visit on Day 57
Primary outcome [2] 327412 0
Changes in clinical labs including the composite of complete blood count (CBC), chemistry, and urinalysis
Timepoint [2] 327412 0
At Baseline and again at Day 57 post intervention
Primary outcome [3] 327413 0
Cutaneous tolerability (a composite of erythema, scaling, dryness, pruritis, and burning/stinging) to be assessed by the PI or trained designee using a Cutaneous Tolerability Assessment scale.
Timepoint [3] 327413 0
Baseline to Days 15, 29 (pre and post-dose) and post intervention at EOS Visit on Day 57
Secondary outcome [1] 391736 0
Percent change in inflammatory lesion counts as conducted by a clinician/investigator
Timepoint [1] 391736 0
Baseline to Days 15, 29 (pre dose) and post intervention at the EOS Visit on Day 57
Secondary outcome [2] 391737 0
Absolute change in inflammatory lesion counts as conducted by a clinician/investigator
Timepoint [2] 391737 0
Baseline to Days 15, 29 (pre dose) and post intervention at the EOS Visit on Day 57
Secondary outcome [3] 391738 0
Change in Investigator’s Global Assessment (IGA-PP)
Timepoint [3] 391738 0
Baseline to Day 29 (pre dose) and post intervention at the EOS Visit on Day 57
Secondary outcome [4] 391739 0
Change in Clinician’s Erythema Assessment (CEA) scale
Timepoint [4] 391739 0
Baseline to Days 15 and 29 (pre dose) and post intervention at the EOS Visit on Day 57
Secondary outcome [5] 391740 0
Change to Patient Reported Outcomes (PRO) with respect to their rosacea symptoms
Timepoint [5] 391740 0
57 days post enrolment
Secondary outcome [6] 395110 0
Blood samples to assess the plasma levels of study medication
Timepoint [6] 395110 0
Pre-dose at Baseline and Days 15, 29 and post intervention on Day 57 (selected sites only)

Eligibility
Key inclusion criteria
#1. Patient has a diagnosis at Screening and Baseline of moderate or severe papulopustular rosacea of the face with:
a. 15 to 75 (inclusive) inflammatory lesions (papules/pustules) on the face.
b. Rosacea severity of moderate (3) or severe (4) on a 5-point static investigator global
assessment for papules & pustules (IGA-PP)
c. CEA score of 3 or 4 (moderate or severe) assessed on the face.
d. No more than 5 large open comedones.

#2. An independent reviewer will review screening photographs to confirm eligibility of the patient for enrolment. No patient may be randomized prior to the confirmation of eligibility by the independent reviewer.

#3. Patient has less than or equal to 2 nodular lesions (greater than or equal to 5 mm in diameter).

#4. Patient agrees to abstain from use of marijuana or cannabidiol (CBD) products throughout the study.

#5. Male patients and their partners must agree and commit to use a barrier method of
contraception throughout the study and for 90 days after last study medication application.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
#1. Patient has used any marijuana products, via any route, within 4 weeks prior to the
Screening Visit. A positive urine drug screen (UDS) for tetrahydrocannabinol (THC) will
exclude the patient. Patient may be deemed eligible if the UDS identifies patient-reported, prescribed medications or appropriate levels of alcohol, as determined by the investigator.

#2. Patient has any significant active infection at Baseline.

#3. Patient has known human immunodeficiency viruses (HIV) infection or hepatitis B or C.

#4. Patient has initiated a hormonal method contraception within 3 months of Baseline or plans to discontinue or change during the study or changed product within 3 months of Baseline.

#5. Patient has used topical acne or rosacea treatments, including metronidazole, azaleic acid, sulfacetamide, salicylic acid, benzyl peroxide, ivermectin, bromonidine, or oxymetazoline within 4 weeks of Baseline.

#6. Patient has used systemic retinoids or high dose (less than 10,000 IU/day) Vitamin A, within 90 days of Baseline.

#7. Patient has used topical or systemic antibiotics within 4 weeks of Baseline.

#8. Patient has used topical (facial) or systemic anti-inflammatories for more than 14
consecutive days in the 4 weeks prior to Baseline.

#9. Patient has used topical (facial) or systemic corticosteroids 4 weeks prior to Baseline.

#10. Patient has used vasodilating agents (e.g., anti-hypertensives, erectile dysfunction
medications, nitroglycerin) 6 weeks prior to Baseline.

#11. Patient has used alpha-adrenergic receptor-blocking agents 6 weeks or alpha-adrenergic agonists 4 weeks prior to Baseline.

#12. Patient has ocular rosacea and/or blepharitis/meibomianitis and requires treatment by an ophthalmologist during the study.

#13. Patient has sunburns, unevenness in skin tones, tattoos, scars, excessive hair (e.g., beard, moustache), freckles, birthmarks, moles, oedematous lesions or other skin damage or abnormality that would result in the inability to perform study assessments.

#14. Patient has an active or potentially recurring skin conditions(s) other than rosacea that may interfere with the rosacea assessment of or require topical or systemic treatment that may affect treatment assessments.

#15. Patient has used systemic or other immunosuppressive medications within 4 weeks of the Baseline Visit (inhaled corticosteroid less than or equal to 1000 µg daily dose is acceptable).

#16. Patient has used phototherapy 14 days prior to Baseline or has had excessive sun exposure with intent to sunbathe or tan or use artificial tanning agents.

#17. Patient has undergone dermatologic procedures to the face including laser, intense pulsed light, chemical peels, salabrasion, dermabrasion or botulinum toxin injection within 4 weeks of the Baseline Visit.

#18. Patient 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 atopic dermatitis.

#19. Patient has participated in another investigational medication or device research study within 30 days of the Screening Visit or five half-lives of the medication, whichever is longer.

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)
Numbered kits
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study is designed to evaluate the safety of BID dosing of BTX 1702 10% (w/w) Gel and BTX 1702 20% (w/w) Gel in patients with papulopustular rosacea. The exploratory analyses of the study medication’s effect on papulopustular rosacea are intended to be used for suggesting hypotheses for further research. All statistical processing will be performed using SAS® unless otherwise stated.
For this study, cutaneous tolerability, burning/stinging, and pruritus are intended to monitor the safety and tolerability of treatment with the BTX 1702 10% (w/w) Gel and BTX 1702 20% (w/w) Gel. The potential effect of BTX 1702 10% (w/w) Gel and BTX 1702 20% (w/w) Gel on the treatment of papulopustular rosacea will be evaluated through evaluation of the IGA-PP, and changes in inflammatory lesion count and CEA from Baseline.
For continuous variables, the mean, SD, median and range will be presented. Categorical variables will be summarised by proportions.
All AEs will be coded using MedDRA. Safety assessments will include TEAEs (AEs that occur in patients who undergo treatment). Patients with TEAEs will be summarised with frequencies and percentages by system organ class and preferred term, severity, and relationship to treatment for each treatment group. TEAEs will be defined as AEs with investigator assessment of possibly related, probably related, or definitely related. In summaries of TEAEs by severity and relationship to study device, patients reporting multiple episodes will be counted once under the worst severity and the strongest relationship, respectively.
The number of patients with at least one AE will be tabulated. The number of AEs for each will also be tabulated. The number of patients and the number of AEs will be tabulated by severity and relationship.
SAEs will be presented by preferred term, severity, outcome, and relationship to study medication; and all SAEs will be listed by patient. In addition, a list of patients who prematurely discontinue from the study due to an AE will be provided.
Changes in laboratory parameters from Baseline to Day 57/EOS will be summarised using shift tables to evaluate for trends. Clinically significant abnormal laboratory findings will be summarised and listed by patient.
Cutaneous tolerability scores for each parameter (erythema, scaling, dryness, pruritus, and burning/stinging) will be summarised for each visit. In addition, the change from Baseline in the mean scores will be summarised for each visit.
Concomitant medications will be mapped to ATC Level 2 using the WHO Drug Dictionary. The number and percentage of patients reporting each medication will be summarised. Medications taken by each patient during the study will be listed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/06/2021
Actual
1/07/2021
Date of last participant enrolment
Anticipated
10/05/2022
Actual
27/05/2022
Date of last data collection
Anticipated
Actual
27/07/2022
Sample size
Target
120
Accrual to date
Final
133
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment outside Australia
Country [1] 23458 0
New Zealand
State/province [1] 23458 0

Funding & Sponsors
Funding source category [1] 307833 0
Commercial sector/Industry
Name [1] 307833 0
Botanix Pharmaceuticals Ltd
Country [1] 307833 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Botanix Pharmaceuticals Ltd
Address
Level 1, 50 Angove Street, North Perth, Western Australia 6005
Country
Australia
Secondary sponsor category [1] 308540 0
None
Name [1] 308540 0
Address [1] 308540 0
Country [1] 308540 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307835 0
Bellberry HREC
Ethics committee address [1] 307835 0
123 Glen Osmond Road, Eastwood, SA 5063
Ethics committee country [1] 307835 0
Australia
Date submitted for ethics approval [1] 307835 0
03/02/2021
Approval date [1] 307835 0
26/03/2021
Ethics approval number [1] 307835 0
2021-02-100
Ethics committee name [2] 311886 0
Central Health and Disability Ethics Committee
Ethics committee address [2] 311886 0
133 Molesworth Street, Wellington, 6011
Ethics committee country [2] 311886 0
New Zealand
Date submitted for ethics approval [2] 311886 0
13/05/2021
Approval date [2] 311886 0
19/07/2021
Ethics approval number [2] 311886 0
21/CEN/129

Summary
Brief summary
Botanix is developing BTX 1702 for the topical treatment of moderate to severe papulopustular rosacea.
This is a randomised, double-blind, vehicle-controlled, parallel-group, Phase 1b study in adult patients, aged 18-65 with moderate or severe papulopustular rosacea. The objective of this study is to determine the safety and tolerability of BTX 1702 10% (w/w) Gel and BTX 1702 20% (w/w) Gel in patients with papulopustular rosacea.
Eligible patients will be enrolled and randomised 1:1:1 to BID treatment with BTX 1702 10% (w/w) Gel, BTX 1702 20% (w/w) Gel, or Vehicle Gel for a planned 56 days. Approximately one hundred and twenty (120) patients (80 active: 40 vehicle) will be enrolled.
The primary outcome for the study is to determine the safety and tolerability of BTX 1702 10% (w/w) Gel, BTX 1702 20% (w/w) Gel, or BTX 1702 Vehicle Gel following 56 days BID applications in patients with papulopustular rosacea.
The safety and tolerability outcome measures will be assessed through the collection and review of AE's, laboratory parameters evaluated throughout the duration of the trial and via information recorded in participant diaries.
Exploratory analysis will be conducted via change in inflammatory lesion counts, change in Investigator’s Global Assessment (IGA-PP), change in Clinician’s Erythema Assessment (CEA) scale and Patient Reported Outcomes (PRO).
Trial website
Trial related presentations / publications
Public notes
Patient will be excluded if they have a confirmed active COVID-19 infection at Baseline Visit. Inclusion of patients that have experienced COVID-19 symptoms (fever, dry cough, tiredness, headache, loss of taste or smell, etc.) within 4 weeks of Baseline is at the discretion of the Investigator.

Contacts
Principal investigator
Name 108674 0
Dr Michael Benson
Address 108674 0
Captain Stirling Medical Centre,
92 Stirling Highway,
Nedlands,
WA 6009
Country 108674 0
Australia
Phone 108674 0
+61 8 9386 1858
Fax 108674 0
Email 108674 0
donnabenson@iinet.net.au
Contact person for public queries
Name 108675 0
Mr Matt Callahan
Address 108675 0
Botanix Pharmacueticals, 3602 Horizon Drive, Suite 160, King of Prussia, PA 19406
Country 108675 0
United States of America
Phone 108675 0
+1 445 300 3403
Fax 108675 0
Email 108675 0
mcallahan@botanixpharma.com
Contact person for scientific queries
Name 108676 0
Mr Anthony Robinson
Address 108676 0
Botanix Pharmacueticals, 3602 Horizon Drive, Suite 160, King of Prussia, PA 19406
Country 108676 0
United States of America
Phone 108676 0
+1 445 300 3410
Fax 108676 0
Email 108676 0
arobinson@botanixpharma.com

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.