This is a multicenter, double-blind, randomized, vehicle-controlled study designed to
compare the efficacy and safety of patidegib gel, 2% and 4% in comparison with that of
vehicle. To be eligible for the study, subjects must be at least 18 years of age and must
meet the diagnostic criteria for basal cell nevus syndrome BCNS.
Approximately 18 subjects who meet the study entry criteria will be randomized in a 1:1:1
ratio to receive patidegib gel 2%, patidegib gel 4%, vehicle gel. One or two tubes of the
assigned study drug will be dispensed to the subject at the Baseline visit. Additional tubes
will be dispensed at subsequent visits through Week 22. The study drug will be applied
topically to the entire face as well as to treatment-targeted surgically eligible basal cell
carcinomas (SEBs) at other anatomical sites twice daily for 26 weeks of treatment.
Information on reported and observed adverse events will be obtained at each visit. An
abbreviated physical examination will be performed at Baseline, Week 14, and Week 26.
At Baseline and Weeks 2, 6, 10, 14, 18, 22, and 26, all visible BCCs (excluding areas below
the knees) will be identified by the Investigator, circled in ink, photographed, measured,
and recorded on a body diagram. Treatment targeted SEBs are defined as the five SEBs on the
face and/or other anatomical areas identified at Baseline as SEBs will be treated during the
26 week treatment phase. If a subject has 5 eligible previously untreated facial SEBs
(excluding tumors on nose and eyelids) these tumors will be the subject's 5 baseline
treatment targeted SEBs and non-facial baseline SEBs will not be treated with study
1. The subject is from 18 to 85 years of age, inclusive.
2. The subject must provide written informed consent prior to any study procedures.
3. The subject must meet diagnostic criteria for BCNS including major criterion #3a plus
one additional major criterion or major criterion #3a plus two of the minor 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
- PTCH1 gene mutation in normal tissue
- 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
4. The subject 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 subject has at Baseline a total of at least 5 previously untreated SEBs (greatest
diameter 5 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 HH (e.g., vismodegib, patidegib, and sonidegib) inhibitors. Baseline
treatment targeted SEBs must not exceed a diameter of > 2cm. 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 subject has 5 or more facial, excluding periorbital and nasal
skin, SEBs at Baseline, non-facial SEBs will not be treatment targeted SEBs.
6. The subject is willing to have SEBs biopsied for biomarkers and plasma to be
collected to measure drug levels as required in the protocol.
7. The subject 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. Subjects 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 subjects must have a negative serum pregnancy test at Screening.
9. If the subject is a male with a female sexual partner who is of child bearing
potential the couple is willing to use highly effective birth control (abstinence,
oral contraceptives, barrier method with spermicide or surgical sterilization) during
the trial and for one month after the last application of the gel.
10. The subject 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 subject 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 subject.
1. The subject is a woman of childbearing potential. This proscription is based on the
key role of the HH pathway in embryogenesis, the known preclinical teratogenic
effects of systemic cyclopamine, a naturally occurring inhibitor of smoothened, and
the unknown level of systemic exposure following topical application in humans.
2. The subject has used topical products to the face or within 5 cm of a treatment
targeted SEB or systemic therapies that might interfere with the evaluation of the
study medication during the study. Specifically these include the use of:
- Topical glucocorticoids 30 days prior to screening
- Retinoids (e.g., etretinate, isotretinoin, tazarotene, tretinoin, adapalene)
systemically or topically or > 5% of an alphahydroxy acid (e.g., glycolic acid,
lactic acid) or 5-fluorouracil or imiquimod (except as topical treatment to
discrete BCCs) systemically or topically to the skin during the six months prior
- Systemic chemotherapy within one year prior to screening. (Note: field therapy
with topically applied treatments can be done as long as they are not applied
within 5 cm of a treatment targeted tumor).
- Known inhibitors of the HH signaling pathway (e.g., vismodegib, patidegib, and
sonidegib) topically or systemically within 6 months of entry into the study.
3. The subject has a history of hypersensitivity to any of the ingredients in the study
4. The subject is unable or unwilling to make a good faith effort to return for all
follow-up visits and tests.
5. The subject has uncontrolled systemic disease.
6. The subject has clinically important history of liver disease, including viral
hepatitis, current alcohol abuse, or cirrhosis.
7. The subject has any condition or situation which in the Investigator's opinion may
put the subject at significant risk, could confound the study results, or could
interfere significantly with the subject's participation in the study. This includes
history of other skin conditions or diseases, metabolic dysfunction, physical
examination findings, or clinical laboratory findings giving reasonable suspicion of
a disease or condition that contraindicates use of an investigational drug or that
might affect interpretation of the results of the study or render the patient at high
risk from treatment complications.
8. The subject has a history of invasive cancer within the past five years excluding
non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of
breast, or chronic lymphocytic lymphoma (Stage 0).
9. The subject has current, recent (within 4 weeks of Baseline visit), or planned
participation in an experimental drug study while enrolled in this study.
10. The subject is unwilling or unable to comply with pregnancy prevention measures.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: 85 Years
Eligible Gender: Both