Evaluation of the Efficacy and Safety of a Thermal Fractional Skin Treatment System (TIXEL®) for the Treatment of Facial and / or Scalp Actinic Keratoses.
Phase: NA
Conditions: Actinic Keratoses
Sponsor: Novoxel Ltd.

Study synopsis. 
EVALUATION OF THE EFFICACY AND SAFETY OF A THERMAL 
FRACTIONAL SKIN TREATMENT SYSTEM (TIXEL®) FOR THE TREATMENT 
OF FACIAL AND/OR SCALP ACTINIC KERATOSES 
 
Study Protocol No:  
CLN 0827 
 
Revision: 
 
 
001 
 
Revision Date: 
 
Jan 16, 2022 
 
Investigational Product: 
Tixel Fractional System  
 
Sponsor: 
 
 
Novoxel Ltd. 
 
 
 
 
43 Hamelaha St. 
 
 
 
 
Poleg Ind. Zone, Netanya,  
Israel 4250573 
 
Contact: 
 
 
Ifat Klein, PhD  
VP of Clinical Affairs 
ifat@novoxel.com 
 
Raphi Shavit 
Chairman, Novoxel Ltd. 
Raphi@novoxel.com 
 
 
 

Study synopsis. 
 
Study Synopsis 
Protocol # 
CLN 0827 
Study Title 
Evaluation of the Efficacy and Safety of a thermal fractional skin treatment 
system (Tixel®) for the treatment of facial and/or scalp actinic keratoses 
Study Device 
Tixel C (by Novoxel)  
Device 
Description 
Tixel technology is a thermal fractional skin treatment system powered by 
Thermo-Mechanical Action technology. Tixel employs a hot titanium tip 
which transfers direct heat to the skin. The proprietary tip is constructed of 
biocompatible temperature resistant titanium alloy cover mounted on gold 
plated copper base. The tip consists of an array of tiny pyramids which are 
heated to a temperature of 400°C. The apex of the pyramids transfers thermal 
energy to skin by very brief controlled contact time.  
Study Design 
and Duration 
Single-center, Prospective, Open Label, with Before-After Study Design. 
Up to 25 subjects will be enrolled to the study to provide at least 20 evaluable 
subjects. Subjects will be examined to determine the severity and extent of 
actinic keratoses.  
All subjects will undergo 1-3 treatments (determined by the investigator 
assessment), 3-4 weeks apart. 
Follow-up visits will be performed after the last treatment visit: 4 weeks (±7 
days) and 12 weeks (±7 days). 
The inclusion criteria would be mild to moderate thickness confluent actinic 
keratoses located to scalp and/or face. 
Each subject will participate in the study for up to 20 weeks.  
Total study duration is estimated to be up to 12 months from enrollment of 
the first subject until last subject visit (including FUs). 
Investigational 
Treatment  
This is a non-invasive thermo-mechanical treatment to the scalp and/or face 
using the Tixel technology. The handpiece will be pressed gently onto the 
scalp/facial skin while transferring heat in a predetermined setting. 
Objectives 
Primary objective 
To evaluate the efficacy of the Tixel technology (device) for the treatment 
of facial and/or scalp actinic keratoses. 
Secondary objectives 
• To evaluate procedure-related adverse reactions. 
• To evaluate Subject’s subjective downtime assessment. 
• To Evaluate the pain of the treatment. 
• To Evaluate the subject’s satisfaction.  

Study synopsis. 
Study Population 
Up to 25 subjects will be enrolled to the study to provide at least 20 evaluable 
subjects presenting with mild to moderate thickness confluent actinic 
keratoses located to scalp and/or face who wish to treat their condition by 
using a non-invasive thermo-mechanical treatment. 
Inclusion 
Criteria: 
1. Male and female, age 18-80 years old. 
2. Skin Phototype I-VI. 
3. Subject has mild to moderate thickness confluent AKs on his/her 
scalp and/or face. 
4. Subject is willing and able to comply with protocol requirements and 
all study visits. 
5. Subject has provided written informed consent. 
Exclusion 
Criteria: 
General 
1. Any patient who has undergone tanning during the 4 weeks prior 
to any treatment session and/or any patient who plans to undergo 
tanning during the 4 weeks following any treatment session 
(patients who may be exposed to the sun for short periods of time 
occasionally are not contra-indicated as long as they apply a high 
SPF sunscreen (>50). 
2. Current active Herpes Simplex infection. 
3. Current skin cancer, malignant sites and/or advanced 
premalignant lesions or moles in the treatment area. 
4. An 
impaired 
immune 
system 
condition 
or 
use 
of 
immunosuppressive medication. 
5. Collagen disorders, keloid formation and/or abnormal wound 
healing. 
6. Any patient who takes or has taken any medications (including 
via topical application), herbal treatment (oral or topic), food 
supplements or vitamins, which may cause fragile skin or 
impaired skin healing during the last 3 months. 
7. Any patient who has used oral retinoids within 6 months prior to 
treatment or less. 
8. Any patient who has a history of bleeding coagulopathies. 
9. Any patient who has tattoos or permanent makeup in the treated 
area. 
10. Any patient who has burned skin, blistered skin, irritated skin, or 
sensitive skin in any of the areas to be treated. 
11. Women who are pregnant (as determined by self-reporting), 
lactating, or less than 3 months post-delivery, possibly pregnant 
or planning a pregnancy during the study period. 
12. Currently participating in or recently participated in another 
clinical trial (within the last 30 days). 
Previous/Current AKs Treatments 
Subject underwent prior treatments for actinic keratoses including: 

Study synopsis. 
13. Prior treatment with ablative laser, any laser or photo-dynamic 
therapy 3 months prior to enrollment. 
14. Any cryotherapy or electrodessication 6 weeks prior to 
enrollment. 
15. Systemic retinoid therapy within 6 months prior to enrollment, 
topical treatment with 5-Fluorouracil cream and/or imiquimod 
cream and/or diclofenac gel 6 months prior to enrollment. 
16.  Prior treatment with Tixel. 
Treatment or treatment area related: 
17. Face cannot be treated due to dermal disorder other than AKs, 
such as infection, surgical treatment etc. 
Medical Conditions  
18. Subject has a systemic disease manifested by AKs (e.g. immune 
suppression). 
19. Significant systemic illness. 
Study 
Evaluations  
Efficacy: 
Lesion count by the investigator, confirmed and documented using 
Standardized high-resolution digital photography of the treatment area 
(before and after marking the present actinic keratoses using a washable 
eyeliner) will be performed for each subject at baseline (before), at each 
treatment visit (prior to the treatment session) and at 4 and 12 weeks FU 
visits.  
 
Safety:  
• Skin safety throughout the study as determined by the investigator 
on site before and after treatments as well as by examining the post-
treatment occurrences of complications and adverse events. 
• Procedure related pain by VAS of 0-10 where a higher score 
indicates greater pain. 
Primary Efficacy 
Endpoint:  
The overall mean percentage reduction in actinic keratoses lesion count 
performed by the investigator manually, confirmed and documented using 
photograph images taken at baseline and at 12 weeks follow-up visit (or 12-
weeks post last treatment if less than 3 treatments were done) (before and 
after marking the present actinic keratoses using a washable eyeliner) 
calculated as the relative change from baseline at 12 weeks. New lesions 
which were not existed in baseline will not be counted. 
Secondary 
Efficacy 
Endpoints:  
• The mean change in actinic keratoses lesion count, performed by the 
investigator manually, confirmed and documented using photograph 
images, from baseline at 4 and 12 weeks follow-up visit. 
• The overall mean percentage reduction in actinic keratoses lesion count 
performed by the investigator manually, confirmed and documented 
using photograph images taken at baseline and at 4 weeks follow-up 
visit (before and after marking the present actinic keratoses using a 
washable eyeliner) calculated as the relative change from baseline at 4 

Study synopsis. 
weeks follow-up visit. New lesions which were not existed in baseline 
will not be counted. 
• Percentage of subjects that demonstrate a 26-50% in reduction in actinic 
keratoses lesion count 3 months after the final treatment. 
• Percentage of subjects that demonstrate a 51-75% in reduction in actinic 
keratoses lesion count 3 months after the final treatment. 
• Percentage of subjects that demonstrate more than 76% in reduction in 
actinic keratoses lesion count 3 months after the final treatment. 
• Subjects’ satisfaction assessed at the final follow-up visit (based on the 
subject experience questionnaire which includes 3 questions relating to 
treatment results, treatment experience and treatment expectations) 
graded on a score of 1- 5; 1 being not satisfied and 5 being very satisfied).  
Safety Endpoints 
• Procedure related AEs 
• Subject subjective downtime assessment - defined as the period of time 
following the procedure during which the subject felt unable/unwilling 
to go out in public due to skin reactions. The assessment will be recorded 
by the subject using the Subject Subjective Downtime Assessment 
following each treatment and will be collected at the site at the follow-
up visits up to 4weeks FU following treatment 3 (third treatment). 
• Procedure related pain by the subjects using VAS for pain of 0-10 where 
a higher score indicates greater pain. 
 
Study Analysis Plan 
Study Design and Objectives 
This is a single-center, prospective, open label study with a before-after study design. The study 
is designed to evaluate the efficacy and safety of treating AKs of the scalp and/or face using 
the Tixel device.  
Study Endpoints 
Primary efficacy endpoint 
The overall mean percentage reduction in AK lesion count performed by the investigator 
manually, confirmed and documented using photograph images taken at baseline and at 12 
weeks follow-up visit (before and after marking the present actinic keratoses using a 
washable eyeliner) calculated as the relative change from baseline at 12 weeks. New lesions 
which were not existed in baseline will not be counted.  
Secondary efficacy endpoints  
• The mean change in actinic keratoses lesion count, performed by the investigator 
manually, confirmed and documented using photographic images, from baseline at 4 
and 12 weeks follow-up visit. 
• The overall mean percentage reduction in AK lesion count performed by the 
investigator manually, confirmed and documented using photograph images taken at 
baseline and at 4 weeks follow-up visit (before and after marking the present actinic 
keratoses using a washable eyeliner) calculated as the relative change from baseline at 
4 weeks. New lesions which were not existed in baseline will not be counted 

Study synopsis. 
• Percentage of subjects that demonstrate a 26-50% in reduction in actinic keratoses 
lesion count 3 months after the final treatment. 
• Percentage of subjects that demonstrate a 51-75% in reduction in actinic keratoses 
lesion count 3 months after the final treatment. 
• Percentage of subjects that demonstrate more than 76% in reduction in actinic keratoses 
lesion count 3 months after the final treatment. 
• Subject satisfaction assessment 
 
Safety Endpoints 
- Procedure related AEs 
- Subject subjective downtime assessment - defined as the period of time following the 
procedure during which the subject felt unable/unwilling to go out in public due to skin 
reactions. 
- Procedure related pain by the subjects using VAS for pain of 0-10 where a higher score 
indicates greater pain. 
Study Hypothesis 
In this study we will test the following hypothesis: 
• Mean reduction in AKs lesion count 3 months after the final treatment will be at least 50%. 
 
Sample Size Estimation 
When the sample size is 20, a two-sided 95% confidence interval for a single mean will extend 
8 from the observed mean, assuming that the standard deviation is known to be 20 and the 
confidence interval is based on the large sample z statistic. 
If the expected rate is 58% the lower bound of the 95% confidence interval will be 50%. 
A result of 58% will ensure with 95% level of confidence that the true percentage is not less 
than 50%. 
REFERENCES  : 
Dixon, W.J., Massey, F.J. Introduction to Statistical Analysis. 4th Edition McGraw-Hill (1983) 
pp. 80-85 
To overcome the expected dropout rate of up to 25% we will recruit up to 25 subjects.  
Randomization and Blinding 
Not relevant: Single arm non-randomized study.  No blinding.  
Full analysis set (FAS) 
The full analysis set (FAS) includes all subjects who were enrolled and underwent at least one 
treatment with the study device. 

Study synopsis. 
Per-Protocol (PP) 
The per-protocol analysis set (PP) will consist of only patients who received the full treatment 
session and have photos from the 3-month follow up visit.  
Statistical Analysis of Analysis Sets 
The FAS analysis set will serve as the main set for safety assessments. The primary efficacy 
assessment will be performed on the PP analysis set and as supportive analysis, on the FAS. 
Statistical Analysis 
General Considerations 
Baseline demographic and other baseline characteristics, together with safety analyses will be 
performed on all enrolled subjects. Baseline values are defined as the last valid value prior to 
first treatment. 
Statistical analyses of safety and secondary efficacy will be mainly descriptive in nature. 
Continuous variables will be summarized by a mean, standard deviation, minimum, 25th 
percentile median 75th percentile and maximum. Categorical variables by a count and 
percentage. Where confidence limits are appropriate, a two-sided 95% confidence interval will 
be constructed. 
The required significance level of findings will be 5%. If statistical tests are performed, they 
will be two-sided and nominal p-values will be presented. 
For comparison of means (continuous variables), the paired t-test or the Wilcoxon rank sum 
test will be used as appropriate. For comparison of proportions (categorical variables), the Chi-
squared test or Fisher’s exact test will be used as appropriate. 
Analyses will be carried out using IBM Corp. Released 2017. IBM SPSS Statistics for 
Windows, Version 25.0. Armonk, NY: IBM Corp. 
Demographic and Other Baseline Variables 
Demographic and baseline condition related characteristics will be tabulated. Continuous 
variables will be summarized by a mean, standard deviation, minimum, 25th percentile, 
median, 75th percentile and maximum, and categorical variables by a count and percentage. 
Disposition of Subjects 
The number of subjects screened and reasons for screening failures will be presented. 
The numbers of subjects who were enrolled will be provided, as well as the reasons for all 
enrollment discontinuations, grouped by major reason (e.g., lost to follow-up, adverse event, 
etc.). A list of discontinued subjects, protocol deviations, and subjects excluded from the 
analyses will be provided as well. 

Study synopsis. 
Efficacy Analysis 
Primary endpoint 
The overall mean percentage reduction in AK lesion count performed by the investigator 
manually, confirmed and documented using photograph images taken at baseline and at 12 
weeks follow-up visit calculated as the relative change from baseline at 12 weeks  will be 
calculated along with 95% confidence interval. 
The Paired T-test or Signed rank test for two means (paired observations) (as is appropriate) 
will be applied for testing the statistical significance of the percentage reduction in in actinic 
keratosis lesion count from baseline at week 12 (compared to 50%). 
Secondary endpoints 
• The mean change in in AK lesion count performed by the investigator manually, 
confirmed and documented using photograph images, from baseline at 4 and 12 weeks  
will be calculated along with 95% confidence interval. 
The Paired T-test or Signed rank test for two means (paired observations) (as is 
appropriate) will be applied for testing the statistical significance of the change  in 
actinic keratosis lesion count from baseline at 4 and 12 weeks. 
• The overall mean percentage reduction in AK lesion count performed by the 
investigator manually, confirmed and documented using photograph images taken at 
baseline and at 4 weeks follow-up visit calculated as the relative change from baseline 
at 4 weeks  will be calculated along with 95% confidence interval. 
The Paired T-test or Signed rank test for two means (paired observations) (as is 
appropriate) will be applied for testing the statistical significance of the percentage 
reduction in in actinic keratosis lesion count from baseline at 4 weeks (compared to 
50%). 
• The percentage of subjects with lesion count reduction from baseline at 3 months 
between 26% and 50% will be calculated along with 95% exact confidence interval for 
proportions. 
• The percentage of subjects with lesion count reduction from baseline at 3 months 
between 51% and 75% will be calculated along with 95% exact confidence interval for 
proportions. 
• The percentage of subjects with lesion count reduction from baseline at 3 months higher 
than 76% will be calculated along with 95% exact confidence interval for proportions. 
• The Subject satisfaction assessment score will be calculated along with 95% confidence 
interval. 
 
Each of the above measures will be summarized by descriptive statistics by data type.  
Safety Analysis 
• Subject assessment of pain, as measured by a VAS score, associated with treatments 
will be tabulated and summarized via descriptive statistics. 
• Skin safety throughout the study as determined by the investigator by examining the 
post-treatment occurrences of complications and adverse events.  
• Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA, most updated version) terminology and presented in tables by System 
Organ Class (SOC) and Preferred Term (PT). 

Study synopsis. 
• Adverse events (AE) will be presented by seriousness, severity, and relation to 
treatment. 
• Concomitant medications entered into the database will be coded using the World 
Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system.  
 
Pooling 
Single center study not relevant. 
Handling of Missing Data 
Missing data will not be imputed.