Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients

Inclusion Criteria

• •1. The participant is from 18 to 85 years of age, inclusive.
• •2. The participant must provide written informed consent prior to any study procedures.
• •3. The participant must meet diagnostic criteria for BCNS, including the first listed major criterion below plus one additional major criterion, or the first listed major criterion below plus 2 of the minor criteria outlined below:
• •Major Criteria:
• •* More than 2 histologically confirmed BCCs or one under the age of 20 years
• •* Odontogenic keratocysts of the jaw proven by histology
• •* Three or more palmar and/or plantar pits
• •* Bilamellar calcification of the falx cerebri (if less than 20 years old)
• •* Fused, bifid, or markedly splayed ribs
• •* First degree relative with basal cell nevus syndrome
• •* Patched 1 (PTCH1) gene mutation in normal tissue
• •Minor Criteria:
• •* Macrocephaly
• •* Congenital malformations: cleft lip or palate, frontal bossing, "coarse face", moderate or severe hypertelorism
• •* Skeletal abnormalities: sprengel deformity, marked pectus deformity, or marked syndactyly of the digits
• •* Radiological abnormalities: bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defects of the hands and feet, or flame shaped lucencies of the hands or feet
• •* Ovarian fibroma
• •* Medulloblastoma
• •4. The participant must have a history of at least 10 BCCs in toto present at Baseline and/or treated within 24 months prior to screening.
• •5. The participant has at Baseline a total of at least 5 previously untreated SEBs (greatest diameter 5 millimeters \[mm\] or greater on the face excluding the nose and periorbital skin, 9 mm or greater on non-facial areas excluding the skin below the knees), as documented clinically by the Investigator at Baseline. Untreated is define as no previous surgical or topical or intralesional drug treatment. Previous treatment with systemically administered drugs more than 6 months prior to Baseline is not considered previous treatment as long as there was no clinical evidence of resistance to oral hedgehog (HH) pathway inhibitors (such as vismodegib, patidegib, and sonidegib). Baseline treatment-targeted SEBs must not exceed a diameter of \>2 centimeters (cm). At least one of these tumors must be appropriate for a 2 mm punch biopsy for biomarker analysis at Baseline and Week 6 visits. If a participant has 5 or more facial, excluding periorbital and nasal skin, SEBs at Baseline, non-facial SEBs will not be treatment-targeted SEBs.
• •6. The participant is willing to have SEBs biopsied for biomarkers and plasma to be collected to measure drug levels as required in the protocol.
• •7. The participant is willing to abstain from application of non-study topical prescription and over the counter medications to facial skin and within 5 cm of treatment targeted SEBs at other anatomical areas for the duration of the study except as prescribed by the Investigator. Moisturizers and emollients are allowable. Participants will be encouraged to use sunscreen with a sunscreen protection factor (SPF) 15 or higher at least once daily on all exposed skin sites.
• •8. Female participants must have a negative serum pregnancy test at Screening.
• •9. If the participant is a male with a female sexual partner who is of childbearing potential the couple is willing to use two effective methods of birth control during the duration of the trial and for one month after the last application of the gel. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (that is, has had menses at any time in the preceding 24 consecutive months), must agree to use 2 effective methods of contraception for the duration of the study and at least 1 month after the last study drug application. The two forms of birth control authorized are defined as the use of a barrier method of contraception (condom with spermicide) in association with one of the following methods of birth control: bilateral tubal ligation; combined oral contraceptives (estrogens and progesterone) or implanted or injectable contraceptives with a stable dose for at least 1 month prior to Baseline; hormonal intra-uterine device (IUD) inserted at least 1 month prior to Baseline.
• •10. The participant is willing to contact the study center after each primary skin care physician (PSCP) visit to provide the study center details of the visit and any treatment of skin tumors.
• •11. The participant is willing to forego treatment of the treatment targeted baseline SEBs except when the Investigator and/or primary care giver believes that delay in treatment potentially might compromise the health of the participant.