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Trial registered on ANZCTR


Registration number
ACTRN12621000860864
Ethics application status
Approved
Date submitted
17/03/2021
Date registered
2/07/2021
Date last updated
4/02/2022
Date data sharing statement initially provided
2/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Topical Carica Papaya Ointment Multi-Arm Trial for adults with mild skin conditions
Scientific title
A 21 day, multicentre, open-label, within-subject controlled study to investigate the efficacy of Carica Papaya fruit ointment on change in irritation and dry skin scores, in adults with mild skin conditions.
Secondary ID [1] 303474 0
Nil known
Universal Trial Number (UTN)
U1111-1266-0384
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild eczema and/or rash 320787 0
Cracked or dry skin on heels 322341 0
Insect bite 322342 0
Sunburn 322343 0
Condition category
Condition code
Skin 318608 318608 0 0
Dermatological conditions
Injuries and Accidents 320009 320009 0 0
Burns

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A diverse population of subjects with existing skin conditions (mild eczema and/or rash, cracked or dry skin on heels, insect bite, sunburn) will present themselves to the trial sites. Subjects will be asked to attend the trial site on day one of the study and the last day of the study. It is possible for subjects to conduct their end of study visit via Telehealth.
Clinical baseline screening will occur on day one of the study and the first treatment of 4% carica papaya fruit ointment will be applied. The 4% carica papaya fruit ointment will be applied three times per day. All subjects will have a treatment site and untreated site identified at screening determined by the PI. Evaluation of dermal reactions at the two sites will be assess clinically using a visual scale that rates the degree of erythema and other signs of cutaneous irritation. Day one subjects will be assigned into a study cohort, trained to apply a measured amount of trial ointment to the treatment site of their skin condition, and trained to use the data collection app. Trial specific containers of 4% carica papaya fruit ointment, dosage spatulas, instruction leaflets, and a phone app for recording results will be supplied to the subjects.
The subject will take two photos of the treated site and two photos of the untreated site every day of the study (one in natural light and one indoors with artificial light). These photos will be taken via the trial app on the patient’s phone and sent directly to the PI for evaluation. Photos are to be taken during daylight hours and just prior to treatment so that there is no (or little) product on the treatment site when the photos are taken. Subjects will record their treatment application via the study app. They will also record the change in irritation and tolerability of 4% carica papaya fruit ointment via the study app.
Subjects in Cohort A (Mild eczema and/or rash), and subjects in Cohort B (cracked or dry skin on heels) will apply treatment and record observations for 21 days.
Subjects in Cohort C (Insect bites), and subjects in Cohort D (Sunburns) will apply treatment and record observations for 10 days.
Intervention code [1] 319764 0
Treatment: Other
Comparator / control treatment
Investigators will locate a treatment and control site on each study participant with the same skin condition and severity. The treated site will be treated with 4% carica papaya fruit ointment 3 times per day and the control site will remain untreated for the duration of the study as a comparator site.
Control group
Active

Outcomes
Primary outcome [1] 326701 0
Primary outcome for Cohort A, C and D will be evaluated by looking at the mean change in irritation score, compared to control from baseline to end of study, via the cumulative irritation score.
Timepoint [1] 326701 0
Irritation score will be assessed daily for Cohort A, C and D from Baseline (day 1) to end of study (day 21 for cohorts A; day 10 for cohorts C and D).
Primary outcome [2] 326702 0
Primary outcome of Cohort B will be evaluated using the Overall Dry Skin (ODS) score. The primary endpoint being Mean change in cumulative ODS score, compared to control, from baseline (day 1) to end of study (21 days).
Timepoint [2] 326702 0
ODS will be assessed daily for Cohort B from Baseline (day 1) to end of study (day 21 )
Secondary outcome [1] 392406 0
Cosmetic outcome assessed by treating Health Care Professional (HCP) on VAS from 0 (poor) to 10 (no visible wound).
Timepoint [1] 392406 0
Assessed by HCP, the VAS score from 0 (poor) to 10 (no visible wound) will be completed at the end of study (day 22 for cohort A and B and day 11 for cohort C and D).
Secondary outcome [2] 392407 0
Local tolerability of ointment evaluated by subjects using 5-point scale on tolerability only for treated area.
Timepoint [2] 392407 0
Evaluated by subjects using 5-point scale on tolerability, with data collected via patient app. Completed at the end of study (day 22 for cohort A and B and day 11 for cohort C and D).
Secondary outcome [3] 396854 0
Changes in erythema scale (0-4) compared with control
Timepoint [3] 396854 0
Erythema score will be assessed daily for all cohorts, from Baseline (day 1) to end of study (day 21 for cohorts A and B; day 10 for cohorts C and D). This will be assessed by the HPC review of the daily photos taken by the study participant.
Secondary outcome [4] 396855 0
Subject rated itch scale (VAS 1-10) compared with control
Timepoint [4] 396855 0
Subject rated itch scale (VAS 1-10) compared with control will be assessed daily by the study participant from Baseline (day 1) to end of study (day 21 for cohorts A and B; day 10 for cohorts C and D).

Eligibility
Key inclusion criteria
Subjects 18-50 years of age, of any race or ethnicity.
1. Not known to be sensitive or allergic to any of the study emollients or their constituents.
2. Provide a signed and dated informed consent form prior to start of any study-related procedures.
3. Able to comprehend and follow the requirements of the study.
4. Females of childbearing potential must have a negative pregnancy test at the Screening/Baseline visit.
5. In the case of a female of childbearing potential, is using one acceptable form of birth control (oral/implant/injectable/transdermal contraceptives, intrauterine device, condom, abstinence, partner’s vasectomy, tubal ligation). Females must have used the same birth control for at least one month prior to starting the study and must continue to use this throughout the duration of the study
6. Subjects suffering from one of the conditions as follows (all definitions are to be interpreted by the treating clinician and/or PI for the study site, as appropriate for the study). Can be self-diagnosed and confirmed by the site PI/study nurse at screening visit. Skin conditions can be present prior to start of study (preexisting). Based on clinical judgement of trial site subject should have active:
a. Mild eczema and/or rash
b. Cracked or dry skin on heels
c. Insect bite
d. Sunburn
7. Fitzpatrick score 1-3
8. Subject must have a smartphone with a functioning camera.
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any visible skin disease at the application site which, in the opinion of the Investigator, will interfere with the evaluation of the test site reaction.
2. Excessive solar damage.
3. Tattoos in the test patches.
4. Known allergic reactions to study components.
5. Pregnancy or lactation.
6. Using systemic/topical corticosteroids within 2 weeks prior to and/or during the study, or systemic/topical antihistamines 72 hours prior to and during the study. Asthma puffers accepted.
7. History of (last 12 months) or are currently being treated for skin cancer and/or hepatitis. Cancer treatment older than 12 months is acceptable.
8. History of, or is currently being treated for, insulin dependent diabetes.
9. Any condition that might compromise study results.
10. Currently participating in any other clinical testing.
11. Has received any investigational drug(s) within 4 weeks prior to study entry.
12. Subjects that have used Papaw ointment on the treatment selected area, in the last 10 days.
13. Subjects with known allergies to fragrance and/or perfumes

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample size calculation
The primary efficacy variable for 3 of the cohorts (A, C and D) is the Cumulative Irritability Score (CIS). Greenspan et al (2003) calculated the standard deviation for the CIS for 8 groups. The SD ranged from 0.04 to 0.56. For the purposes of the sample size calculation the SD was conservatively estimated to be 0.75 given that the SD may vary between cohorts. The difference between the means was estimated to be 0.40 CIS units. The level of significance was set to 0.05 for all cohorts with a 2-sided test. With these settings a sample size of 30 will provide a power of 80%. The sample size was increased by 10% to 33 to allow for early withdrawals.
The Overall Dry Skin (ODS) score assesses dryness via a 5-point scale (0—4). The range from 0 to 4 can be thought of as 4 standard deviations. Therefore, the standard deviation was estimated conservatively to be one quarter of the range; that is 1.0 units. The difference between the means was estimated to be 0.5 units. The level of significance was set to 0.05 with a 2-sided test. With these settings a sample size of 34 will provide a power of 80%. The sample size was increased by 10% to 36 to allow for early withdrawals.

Safety Variables:
Adverse events (AEs), all AEs, AEs grade 3 or 4, AEs leading to treatment interruption and discontinuation, serious adverse events (SAEs), premature discontinuation from study and treatment.

Study Populations:
The main analysis population for the efficacy analysis will be the intent-to-treat (ITT) population, which will include all subjects enrolled in the study irrespective of whether they have received study treatment or not. ITT1 to ITT4 will correspond to the ITT population for each cohort (Cohort 1 to Cohort 4, respectively).
The per-protocol (PP) population will not be defined due to the small number of subjects per cohort, but protocol deviations will be listed.

Statistical Model:
Each participant will provide a treated site, and a control site, which represents the classical paired observations. Therefore, the paired t-test will be used to test the difference between mean Cumulative Irritation Score (CIS) for the treated sites versus the control sites. The null hypothesis is that mean CIS for the treated sites equals mean CIS for the control sites. The null hypothesis will be tested against the alternative hypothesis that the means are not equal. The Overall Dry Skin Score ODS score will also be analysed with the paired t-test.

Stopping rules for enrolment and screening:
If no subjects are enrolled within any cohort after 3 months from the start of the study, as described above, then that particular cohort will be closed and enrolment for that cohort will be stopped. Sample numbers in the remaining cohorts will be increased.

Stopping rules for each cohort:
Interim analysis to occur once 50% recruitment has been achieved (67 subjects)
If a clear clinical benefit has been observed for subjects in the cohort, then enrolment for that cohort will continue.
If the ointment is considered to be non-efficacious in a cohort, the sponsor may decide to close the cohort, and increase subject enrollment numbers in the remaining cohorts.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/07/2021
Actual
26/07/2021
Date of last participant enrolment
Anticipated
20/01/2022
Actual
13/01/2022
Date of last data collection
Anticipated
31/01/2022
Actual
24/01/2022
Sample size
Target
135
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 18938 0
Austrials - Taringa - Taringa
Recruitment hospital [2] 18939 0
Austrials - Wellers Hill - Tarragindi
Recruitment hospital [3] 19909 0
Northern Beaches Clinical Research - Brookvale
Recruitment hospital [4] 21230 0
Griffith University Clinical Trials Unit - Southport
Recruitment postcode(s) [1] 33334 0
2100 - Brookvale
Recruitment postcode(s) [2] 33445 0
4068 - Taringa
Recruitment postcode(s) [3] 33446 0
4121 - Tarragindi
Recruitment postcode(s) [4] 36099 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 307893 0
Commercial sector/Industry
Name [1] 307893 0
Lucas' Papaw Remedies
Country [1] 307893 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Lucas' Papaw Remedies
Address
15 Durbell Street
Acacia Ridge
Brisbane, QLD, 4110
Country
Australia
Secondary sponsor category [1] 308604 0
None
Name [1] 308604 0
Address [1] 308604 0
Country [1] 308604 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307891 0
Bellberry Limited
Ethics committee address [1] 307891 0
123 Glen Osmond Rd, Eastwood SA 5063
Ethics committee country [1] 307891 0
Australia
Date submitted for ethics approval [1] 307891 0
02/02/2021
Approval date [1] 307891 0
21/06/2021
Ethics approval number [1] 307891 0

Summary
Brief summary
The aim of this clinical trial is to determine if the study ointment assists with skin conditions including mild eczema and/or rash, cracked or dry skin on heels, insect bites and sunburn. The study ointment is currently in use in Australia as a topical treatment. The effectiveness of the study ointment for skin conditions has not been assessed in a clinical trial.
The study team will identify a treatment patch and a similar patch that will not be treated and will be the control site. You will be asked to apply the study ointment 3 times per day to the treatment patch and not to the control patch. Participants with mild eczema and/or rash and cracked or dry skin on heels will be treated with the ointment for 21 consecutive days. Participants with insect bites and sunburn will be treated with the ointment for 10 consecutive days. The response will be assessed using daily photos that will be assessed by the study team using a skin irritation score as well as by a participant rating tool.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108838 0
Dr Anthony McGirr
Address 108838 0
Northern Beaches Clinical Research
Suite 201, 694-696 Pittwater Road
Brookvale, NSW, 2100
Country 108838 0
Australia
Phone 108838 0
+61 2 9905 1282
Fax 108838 0
Email 108838 0
[email protected]
Contact person for public queries
Name 108839 0
Ari Dearnley
Address 108839 0
Molecule2Market
Ground Floor, 35 Cotham Road,
Kew, VIC, 3101
Country 108839 0
Australia
Phone 108839 0
+61 0409 746 142
Fax 108839 0
Email 108839 0
[email protected]
Contact person for scientific queries
Name 108840 0
Sam Vohra
Address 108840 0
Avion Medical
10 Oxley Road, Hawthorn
Hawthorn, VIC, 3122
Country 108840 0
Australia
Phone 108840 0
+61 450 556 969
Fax 108840 0
Email 108840 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All individual participant data will be de-identified and only de-identified pooled data will be made publicly available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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