Tolerance and Performance of Cyto-selective Difluoroethane-based Cryotherapy in the Treatment of Brown Spots.
Condition: Solar Lentigo; Senile Lentigo; Post-inflammatory Hyperpigmentation
MeSH terms: Hyperpigmentation; Lentigo
Study type: Interventional

Summary: 
      CS5_3 aims to evaluate the tolerance and to adjust the mode of administration of 4 different
      conditions of cryotherapy treatments applied on the brown spots of the face and hands with 3
      prototypes. A brown spot is defined as solar or senile lentigo and post-inflammatory
      hyperpigmentation (PIH).

      Each treatment corresponds to a combination of a specific sequence of a cryogenic spray and
      of a frequency of application.

      The study will evaluate 3 prototypes :

        -  Prototype 1 : SN from (816-v1 001) to (816-v1 100)

        -  Prototype 2 : SN from (816-v1 101) to (816-v1 150)

        -  Prototype 3 : SN from (816-v1 151) to (816-v1 200)

      Prototypes will be applied on the face and hands according to specific frequencies of
      application.
    

Detailed description: 
      Hyperpigmentation is a problem in all skin types. Safe depigmentation is a challenge.
      Cryotherapy with liquid nitrogen at -70 °C has been used in the treatment of solar skin
      lesions for many years but causes considerable damage.

      Solar/senile lentigo is a harmless patch of darkened skin. It results from exposure to
      ultraviolet (UV) radiation, which causes local proliferation of melanocytes and accumulation
      of melanin within the skin cells (keratinocytes). Solar/senile lentigos or lentigines are
      very common, especially in people over the age of 40 years.

      A solar/senile lentigo is a flat, well-circumscribed patch. It can be round, oval or
      irregular in shape. Colour varies from skin-coloured, tan to dark brown or black, and size
      varies from a few millimetres to several centimetres in diameter. They can be slightly scaly.
      Solar/senile lentigines are found as groups of similar lesions on sun-exposed sites,
      particularly the face or the back of hands.

      Cryotherapy is more and more used to improve skin appearance and currently used to treat
      lentigo spot. However, the cryogenic gas (conventional cryotherapy - liquid nitrogen) creates
      a dermabrasion of the skin surface and person receiving this kind of treatment presents an
      impaired skin during a few days following the treatment as temporary damage of stratum
      corneum, erythema, scars, burns.

      Following the side effects occurring after conventional cryotherapy application, the Sponsor
      has developed some devices using difluoroethane, manufactured by CRYONOVE PHARMA, already
      available on the local and international markets, e.g. CRYOBEAUTY MAINS and CRYOBEAUTY CORPS.

      To continue its research and development activities, the sponsor has selected other sequences
      of a specific cryogenic spray (3 prototypes of devices for face and hands used according to
      different frequencies of application, i.e. 4 conditions evaluated) which has been used
      effectively and safely for lentigos treatment in Fitzpatrick phototypes I to IV on the face,
      with benefit for the subjects without any adverse safety outcomes. There is therefore a need
      to test the devices for lentigo and PIH on darker skin phototypes (V and VI according to
      Fitzpatrick scale), which also encounter hyperpigmentation challenges.

      The rational for this study is to obtain a proof of performance on a representative panel
      sufficient to get statistically significant results of the expected effects. This will
      complete the data obtained during the previous proof of performance studies already performed
      on small panels as prerequisite data and have demonstrated an acceptable benefit/risk ratio.

      Design:

      The study is a proof of performance designed to be interventional, monocentric, randomized
      and double blinded.

      Intervention:

      Application on the skin of the face and the hands for the prototypes (816-v1 001) to (816-v1
      200).

        -  Each spot will be treated by a defined prototype (always the same prototype on the same
           spot throughout the study) as given by a randomization list.

        -  Each spot will be treated 6 times during the study:

             -  At D0, D1, D2, D3, D4 and D5) (condition 1)

             -  At D0, D7, D14, D21, D28 and D35 (condition 2).

             -  At D0, D14, D28, D42, D56 and D70 (conditions 3).

             -  At D0, D14, D28, D42, D56 and D70 (conditions 4).

      The distribution of the spots per phototypes and per condition is the following:

        -  Before any application, the dermatologist will collect the adverse events if any and
           will decide if the period between two consecutive applications should be extended or
           not.

        -  Before the application, the dermatologist will verify that the skin has not been treated
           by cosmetic products (no presence of cream that could interfere with the treatment) and
           is dry.

        -  Administration by the responsible technician (previously trained).

        -  Discontinuation of the treatment after the disappearance of the spot (to be confirmed by
           Dermatologist).

        -  Subjects will be lying supine, and the prototypes will be administered upside down for
           the applications on the face and sitting for the applications on the hands. For the
           application on the hands, the hands will be placed flat on the table and the prototypes
           will be applied upside down.

        -  During applications on the face, subjects will wear safety goggles protecting the eyes
           from cryogenic gas.

        -  From the start of the study until 2 months after the last treatment, volunteers will
           apply a sunscreen SPF 50+ (La Roche Posay, Anthelios if available to their hands and
           face in case of sun exposure). In case of prolonged sun exposure, application will be
           repeated as defined in the instructions for use.
    

Intervention name(s): Prototypes (816-v1 001) to (816-v1 050); Prototype (816-v1 051) to (816-v1 100); Prototypes (816-v1 101) to (816-v1 150); Prototypes (816-v1 151) to (816-v1 200)
Intervention type(s): Device; Device; Device; Device
Intervention description(s): Application on brown spots located on the face and/or the hand (6 treatments during the study). An operator previously trained by the dermatologist will apply the study device to the patient's face or/and hand. Subjects will be lying supine, and the prototypes will be administered upside down for the applications on the face and sitting for the applications on the hands. For the application on the hands, the hands will be placed flat on the table and the prototypes will be applied upside down. During applications on the face, subjects will wear diving goggles protecting the eyes from cryogenic gas.; Application on brown spots located on the face and/or the hand (6 treatments during the study). An operator previously trained by the dermatologist will apply the study device to the patient's face or/and hand. Subjects will be lying supine, and the prototypes will be administered upside down for the applications on the face and sitting for the applications on the hands. For the application on the hands, the hands will be placed flat on the table and the prototypes will be applied upside down. During applications on the face, subjects will wear diving goggles protecting the eyes from cryogenic gas.; Application on brown spots located on the face and/or the hand (6 treatments during the study). An operator previously trained by the dermatologist will apply the study device to the patient's face or/and hand. Subjects will be lying supine, and the prototypes will be administered upside down for the applications on the face and sitting for the applications on the hands. For the application on the hands, the hands will be placed flat on the table and the prototypes will be applied upside down. During applications on the face, subjects will wear diving goggles protecting the eyes from cryogenic gas.; Application on brown spots located on the face and/or the hand (6 treatments during the study). An operator previously trained by the dermatologist will apply the study device to the patient's face or/and hand. Subjects will be lying supine, and the prototypes will be administered upside down for the applications on the face and sitting for the applications on the hands. For the application on the hands, the hands will be placed flat on the table and the prototypes will be applied upside down. During applications on the face, subjects will wear diving goggles protecting the eyes from cryogenic gas.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment