Neoplasms

All Conditions

Symptoms and General Pathology

Musculoskeletal Diseases

Mouth and Tooth Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Carcinoma

Syndrome

Carcinoma, Basal Cell

Basal Cell Nevus Syndrome

Nevus, Pigmented

Nevus

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Basal Cell

Cysts

Odontogenic Cysts

Jaw Cysts

Bone Cysts

Neoplastic Syndromes, Hereditary

Bone Diseases

Bone Diseases, Developmental

Jaw Diseases

Stomatognathic Diseases

Congenital Abnormalities

Abnormalities, Multiple

Genetic Diseases, Inborn

Nevoid Basal Cell Carcinoma Syndrome

Patidegib gel 2%, applied topically, twice daily for 26 weeks

Patidegib gel 4%, applied topically, twice daily for 26 weeks

Vehicle gel, applied topically, twice daily for 26 weeks

Patidegib

Vehicle gel

John Lear, MD

Multicenter, double-blind, randomized, vehicle-controlled study that evaluates the efficacy and safety of patidegib gel 2% and 4% in comparison with vehicle in participants at least 18 years of age that meet the diagnostic criteria for basal cell nevus syndrome (BCNS). Participants will be randomized to receive patidegib gel 2%, patidegib gel 4%, or the vehicle gel for a 26-week treatment period.

Participants 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 participant 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 6, 10, 14, 18, 22, and 26, all visible basal cell carcinomas (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 (defined as the 5 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 participant has 5 eligible previously untreated facial SEBs (excluding tumors on nose and eyelids) these tumors will be the participant's 5 baseline treatment-targeted SEBs and non-facial baseline SEBs will not be treated with study drug. Tumors to be measured and mapped include the 5 baseline treatment-targeted tumors as well as all other facial tumors including those on the eyelids and the nose. In addition, up to 10 non-treatment-targeted non-facial tumors will also be measured and mapped.

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

Double-Blind, Randomized, Vehicle-Controlled Proof of Concept Clinical Trial of Patidegib Gel 2%, 4%, and Vehicle to Decrease the Number of Surgically Eligible Basal Cell Carcinomas in Gorlin Syndrome Patients

The ISGTA is a scale with scores ranging from 0 (clear), 1 (almost clear), 2 (minimal residual tumor), to 3 (clearly visible tumor). The Investigator assessed each Baseline treatment-targeted SEB at Weeks 6, 10, 14, 18, 22, and 26. SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The percentage of Baseline treatment-targeted SEBs evaluated as being clear or almost clear at Week x (Week x = Week 6, 10, 14, 18, 22 or 26) based on the ISGTA scale was calculated as follows: (Number of baseline treatment-targeted SEBs with ISGTA score of 0 or 1 at Week x) / (Number of Baseline treatment-targeted SEBs) \* 100. Missing data were imputed using LOCF. The percentage of responders achieving clear (0) or almost clear (1) on the ISGTA scale are presented by Week.

SEBs were defined as clinically diagnosed basal cell carcinoma (BCC) 5 millimeters (mm) or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The percent change in greatest diameters of treatment-targeted surgically eligible basal cell carcinomas (SEBs) from Baseline to Week 26 was calculated as follows: (sum \[Baseline\] - sum \[Week 26\] / sum \[Baseline\] \* 100), where sum = the greatest diameters of Baseline treatment-targeted SEBs and positive numbers represent decrease in tumor size and negative numbers to represent increase in tumor size. Missing values were imputed using Last-Observation Carried Forward (LOCF).

SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9-mm or greater at sites other than the face. A single baseline SEB designated as a treatment targeted tumor at Baseline was biopsied first at Baseline and again following 6 weeks of treatment. This was used to assess percent change in GLI1 mRNA levels as follows: (Baseline - Week 6) / Baseline \* 100, where positive numbers to represent decrease in GL1 mRNA level and negative numbers to represent increase in GL1 mRNA level. Any missing values were not imputed; all available data is summarized.

All serious adverse events (SAEs) and all other non-serious adverse events (AEs) regardless of causality are located in the Reported AE Module. AEs considered as related where categorized by the Investigator as either definitely related, probably related, or possibly related. Treatment-emergent AEs are those with an onset after use of study drug.

All SAEs and all other non-serious AEs, regardless of causality, are located in the Reported AE Module. The number of participants reporting administrative-site, skin condition treatment-emergent AEs considered related to study drug by the Investigator are presented below. Treatment-emergent AEs are those with an onset after use of study drug.

Facial SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin. A new facial SEB was defined as an SEB first noted on the face after Week 2 that developed at a site where there was no visible BCC of any size at Baseline or Week 2. New facial SEBs were investigated for participants on vehicle gel versus participants on patidegib 2% and 4% gel. Missing values were imputed using LOCF.

Facial SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin. A new facial SEB was defined as an SEB first noted on the face after Week 2 that developed at a site where there was no visible BCC of any size at Baseline or Week 2. New facial SEBs were investigated for participants on vehicle gel versus participants on patidegib 2% and 4% gel. Missing values were imputed using LOCF. The mean number of new SEBs (number per participant) are presented. No measure of dispersion/precision was calculated.

SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The percent change in greatest diameters of Baseline treatment-targeted SEBs from Baseline to Week x (Week 6, 10, 14, 18, or 22) was calculated as follows: (sum \[Baseline\] - sum \[Week x\] / sum \[Baseline\] \* 100), where sum = the greatest diameters of Baseline treatment-targeted SEBs, and positive numbers to represent decrease in tumor size and negative numbers to represent increase in tumor size. Missing values were imputed using LOCF.

Central facial SEBs were defined as those located on the nose or periorbital area (eyelids) which were 3 mm or greater at Baseline. The percent change from Baseline to Week x (Week x = Weeks 6, 10, 14, 18, 22, or 26) in central facial SEBs was calculated as follows: \[sum (Baseline) - sum (Week x)\] / \[sum (Baseline)\] \* 100 where sum = the greatest diameters of Baseline treatment-targeted SEBs where positive numbers to represent decrease in tumor size and negative numbers to represent increase in tumor size. Missing values were imputed using LOCF.

The proportion of non-central facial BCCs that at Baseline measured a greatest diameter of \< 5 mm and increased to a diameter of ≥ 5 mm by Week x (Week x = Weeks 6, 10, 14, 18, 22, or 26) were calculated for each participant as follows: (Number of non-central facial BCCs with greatest diameter ≥ 5 mm at Week x) / (Number of non-central facial BCCs with greatest diameter \< 5 mm at Baseline). Missing values were imputed using LOCF.

SEBs were defined as clinically diagnosed BCC 5 mm or greater in diameter on the face, excluding the nose and periorbital skin, and 9 mm or greater at sites other than the face. The proportion of Baseline treatment-targeted SEBs that at the end of 26 weeks of treatment were no longer large enough to be classified as SEBs (that is, the proportion of Baseline treatment targeted SEBs on the face that became \< 5 mm in greatest diameter and non-facial Baseline treatment targeted SEBs that became \< 9 mm in greatest diameter) were calculated for each participant as follows:

(Number of Baseline treatment-targeted facial SEBs with greatest diameter \< 5 mm) + (Baseline treatment targeted non-facial SEBs with greatest diameter \< 9 mm) / Number of baseline treatment targeted SEBs.

Missing values were imputed using LOCF.

PellePharm, Inc.

Applied topically twice daily for 26 weeks

Patidegib Gel 2%

Patidegib Gel 4%

Vehicle Gel

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United Kingdom

Region of Enrollment

Weight data at baseline was not available for 1 participant in the Patidegib Gel 4% treatment arm.

Weight

Participants who received at least 1 dose of study drug.

Chief Medical Officer

By tumor per protocol population includes all treatment-targeted tumors except tumors that were biopsied and excludes tumors that did not meet protocol criteria.

Clinical Efficacy: Percent Change in Tumor Size of Treatment-targeted Surgically Eligible Basal Cell Carcinomas (SEBs) From Baseline

Participants who received at least 1 dose of study drug who had evaluable GLI1 mRNA data at Baseline and Week 6.

Molecular Efficacy: Percent Change in the Hedgehog (HH) Signaling Pathway Target Gene Glioma-associated Oncogene Homolog 1 (GLI1) Messenger Ribonucleic Acid (mRNA) Levels From Baseline

All enrolled participants who were randomized, received at least 1 confirmed dose of study drug, and had at least 1 post-baseline safety assessment.

Safety and Tolerability Assessment of Treatment With Patidegib Gel: Number of Participants With a Treatment-emergent Adverse Event Causally Related to Study Drug

Application site alopecia

Application site dermatitis

Application site pain

Application site rash

Application site reaction

Safety and Tolerability Assessment of Treatment With Patidegib Gel: Number of Participants With Treatment-emergent Administrative Site Skin Condition AEs Causally Related to Study Drug

Patidegib: 2% or 4% gel applied topically twice daily for 26 weeks

Patidegib Gel

The Number of Participants Reporting New SEBs on the Face From Baseline for the Combined Patidegib Treatment Groups

The Mean Number of New SEBs on the Face for the Combined Patidegib Treatment Groups

The Mean Number of New SEBs on the Face for the Combined Patidegib Treatment Groups by Tumor Population

Week 6

Week 10

Week 14

Week 18

Week 22

Percent Change in Baseline Treatment-targeted SEBs Tumor Size From Baseline

Week 26

Participants who received at least 1 dose of study drug and who had a central facial SEB at Baseline.

Percent Change in Central Facial SEBs From Baseline

Participants who received at least 1 dose of study drug with non-central facial BCCs \< 5 mm at Baseline.

Spots Global Cancer Trial Database for nevus syndrome