Clinical trial NCT05203263: Tolerance and Mode of Administration of Cyto-selective Cryotherapy Treatments in Face Brown Spots: Proof of Concept
Official title: Evaluation of the Tolerance and the Mode of Administration of Cyto-selective Difluoroethane-based Cryotherapy in the Treatment of Brown Spots
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Solar Lentigo
Keywords: Lentigo
Melanosis
melanocyte
melanosome
Hyperpigmentation
Pigmentation Disorders
Skin Diseases
Lead sponsor: Cryonove Pharma
Sponsor class: INDUSTRY
Collaborators: name: Dermatech
name: CEISO
name: INNOVSOLUTION
First posted: 2022-01-24
Enrollment: 23
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Solar lentigos or lentigines are harmless patch of darkened skin, of different sizes and colors, due to the exposure to UV radiation. They are very common, especially in people over the age of 40 years old. Solar lentigines appears as clusters of similar lesions on sun-exposed sites, such as the face or the back of the hands.

Conventional cryotherapy is increasingly used to improve the skin appearance and especially to treat lentigo spots. However, the application of conventional cryotherapy is followed by temporary side effects including pain at application, hypo- and hyperpigmentation, crust, scars, burns, erythema... for a few days after administration and that can persist during several months.

In this context, the sponsor has developed a treatment using cyto-selective cryotherapy, that treats only the melanocytes responsable of brown spots while preserving other cells of the epidermis. Several sequences of pulverization of cryogenic gas have been designed. It seems interesting for the sponsor to study some ways of applications of the selected sequences. i.e. 5 conditions evaluated) that could be used for the treatment of lentigos with the same clinical benefit and with better safety results for patients .

(CS4_2) proof of concept, interventional, monocentric, randomized and double blinded study, aims to evaluate the tolerance and the mode of administration of cyto-selective difluoroethane-based cryotherapy in the treatment of brown spots.

The main objective of the study is to evaluate the tolerance and to adjust the mode of administration of 3 different cryotherapy treatments (3 prototypes) applied on the brown spots of the face. Each treatment corresponds to a specific sequence of a cryogenic spray.

Detailed description: Prototypes (810A-v1), (810B-v1) and (810C-v1) will be applied on brown spots located on the face. Regarding the randomization list, each spot will be treated by a defined prototype / device (same prototype /device will be used to treat the same spot all along the study).

Each spot will be treated 6 times during the study:

* At Day 0, Day 1, Day 2, Day 3 Day 4 and Day 5 for the prototypes (810A-v1) (condition 1) and (810B-v1) (condition 2).
* At Day 0, Day 7, Day 14, Day 21, Day 28 and Day 35 for the prototypes (810A-v1) (condition 3) and (810C-v1) (condition 4).
* At Day 0, Day 14, Day 28, Day 42, Day 56 and Day 70 for the prototype (810C-v1) (condition 5, considered as reference).

Prior to any study device application, the dermatologist will assess the adverse events and decide whether the period between two consecutive applications should be extended or not. The dermatologist will verify that the skin has not been treated with cosmetic products (no cream, peeling, dermabrasion, laser treatment... that could interfere with the treatment) and that is dry.

The procedure will take place at the investigation site. An operator previously trained by the dermatologist will apply the study device to the patient's brown spots.

Subjects will lie down and the device will be administered upside down. During the applications, subjects will wear diving goggles (provided by the CRO) to protect the eyes from the cryogenic gas.

Treatments will be stopped when a total of 6 applications for the prototypes will be delivered or as soon as a spot will be considered disappeared by the investigator. Otherwise the study will continue (tolerance report, etc.) until all conditions are completed.

Eligibility criteria: Inclusion Criteria:

* Phototype II et III (according with Fitzpatrick scale)
* Featuring brown spots (solar lentigos) on the face ≥ 3mm to 6 mm in diameter (at least 2-3 spots per subject).
* Agreeing not to be exposed to the sun (or artificial UV) during the study.
* Informed, having undergone a general clinical examination attesting to his/her ability to participate in the study.
* Having given written consent for participation in the study.
* No suspicion of carcinoma after investigation by a dermatologist.

Exclusion Criteria:

* Having performed cosmetic treatments (exfoliants, scrubs or self-tanners, facials, UV...) in the month before the start of the study, at the level of the face.
* Having applied a depraving product in the month prior to the start of the study, at the level of the face.
* Having performed cosmetic treatments in a dermatologist (laser, intense pulsed light, peeling, creams, cryotherapy ...), at the level of the face in the last 6 months.
* With dermatosis, autoimmune disease, systemic, chronic or acute disease, or any other pathology that may interfere with treatment or influence the results of the study (people with diabetes or circulatory problems, allergic to cold, Raynaud's syndrome...).
* Receiving treatment by general or local (dermo corticoids, corticosteroids, diuretics ...) likely to interfere with the evaluation of the parameter studied.
* Participating in another study or being excluded from a previous study.
* Unable to follow the requirements of the protocol.
* Vulnerable: whose ability or freedom to give or refuse consent is limited.
* Major protected by law (under guardianship, under curatorship, safeguarding justice...).
* People unable to read and write Ukrainian language.
* Unable to be contacted urgently over the phone.

For female subjects:

* Pregnant woman (or wishing to be pregnant during study) or while breastfeeding.
* A woman, who does not use effective methods of contraception.

Primary outcomes:
measure: Change from baseline skin hyperpigmentation
timeFrame: - Conditions 1 and 2: Day0, Day1, Day2, Day3, Day4, Day5, Day14 and Day28 - Conditions 3 and 4: Day0, Day1, Day2, Day3, Day7, Day14, Day21, Day28, Day 35 and Day42 - Condition 5 (Ref): Day0, Day1, Day2, Day3, Day14, Day28, Day42, Day56, Day70 and Day84
measure: Change from baseline skin hypopigmentation
timeFrame: - Conditions 1 and 2: Day0, Day1, Day2, Day3, Day4, Day5, Day14 and Day28 - Conditions 3 and 4: Day0, Day1, Day2, Day3, Day7, Day14, Day21, Day28, Day35 and Day42 -Condition 5 (Ref): Day0, Day1, Day2, Day3, Day14, Day28, Day42, Day56, Day70 and Day84
measure: Change from baseline skin appearance (Edemas, blisters, bubbles, scars, erythema)
timeFrame: - Conditions 1 and 2: Day0, Day1, Day2, Day3, Day4, Day5, Day14 and Day28 - Conditions 3 and 4: Day0, Day1, Day2, Day3, Day7, Day14, Day21, Day28, Day35 and Day42 -Condition 5 (Ref): Day0, Day1, Day2, Day3, Day14, Day28, Day42, Day56, Day70 and Day84
measure: Change from baseline skin sensation (itching, tingling, burning sensations)
timeFrame: - Conditions 1 and 2: Day0, Day1, Day2, Day3, Day4, Day5, Day14 and Day28 - Conditions 3 and 4: Day0, Day1, Day2, Day3, Day7, Day14, Day21, Day28, Day35 and Day42 -Condition 5 (Ref): Day0, Day1, Day2, Day3, Day14, Day28, Day42, Day56, Day70 and Day84
measure: Post treatment pain
timeFrame: Day 0 (Time1 defined as 15 minutes post-treatment)
measure: Change from baseline skin color
timeFrame: - Conditions 1 and 2: Day0, Day14 and Day28 - Conditions 3 and 4: Day0, Day7, Day14, Day21, Day28, Day35 and Day42 - Condition 5 (Ref): Day0, Day14, Day28, Day42, Day56, Day70 and Day84
measure: Change from baseline spots visibility
timeFrame: - Conditions 1 and 2: Day0, Day1, Day2, Day3, Day4, Day5, Day14 and Day28 - Conditions 3 and 4: Day0, Day1, Day2, Day3, Day7, Day14, Day21, D28, Day35 and Day42 - Condition 5 (Ref): Day0, Day1, Day2, Day3, Day14, Day28, Day42, Day56, Day70 and Day84
Secondary outcomes:
measure: Efficacy self-assessment
timeFrame: - Conditions 1 and 2: Day0, Day1, Day2, Day3, Day4, Day5, Day14 and Day28 - Conditions 3 and 4: Day0, Day1, Day2, Day3, Day7, Day14, Day21, Day28, Day35 and Day42 - Condition 5 (Ref): Day0, Day1, Day2, Day3, Day14, Day28, Day42, Day56, Day70 and Day84
Other outcomes:
Locations:
city: Zhytomyr
country: Ukraine
facility: VIDNOVLENNYA medical center
Study officials:
References: