Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome (Gorlin Syndrome)

A Multicenter, Randomized, Double-blind, Vehicle-controlled, Phase 3 Efficacy and Safety Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome

This is a global, multicenter, randomized, double-blind, stratified, vehicle-controlled study of the efficacy and safety of Patidegib Topical Gel, 2%, applied topically twice daily to the face of adult participants with Gorlin syndrome. Participants will be required to apply the investigational product for 12 months. The primary endpoint is a comparison between the two treatment arms of the number of new BCCs that develop over the 12 month period.

Study Overview

• Status: Completed
• Conditions: Basal Cell Nevus Syndrome
• Intervention / Treatment: Drug: Patidegib Topical Gel, 2%; Drug: Patidegib Topical Gel, Vehicle

Detailed Description

An open-label, extension safety and tolerability study is planned for at least 12 months duration following the end of this study. All participants who complete the Month 12 Exit Visit having demonstrated adequate compliance with application of the Investigational Product (IP) without major Protocol Deviations (PDs) during the study will be eligible for participation in the extension study.

All participants will be contacted by phone approximately 30 days following the Exit or Discontinuation Visit to determine if the participant has experienced any new adverse events (AEs)/serious AEs (SAEs) since discontinuation/completion of study treatment.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • PellePharm Investigative Site
  • Leuven, Belgium, 3000
    • PellePharm Investigative Site
• Canada
  • Toronto, Canada, M5S1B2
    • PellePharm Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Clinical Trials Unit - The Skin Care Centre
• Denmark
  • Copenhagen, Denmark
    • PellePharm Investigative Site
• France
  • Bordeaux Cedex, France, 33075
    • Hopital Saint-Andre - CHU Bordeaux
  • Lille Cedex, France, 59037
    • CHRU de Lille - Hopital Claude Huriez
  • Marseille, France, 13395
    • CHU La Timone
  • Nantes, France, 44093
    • PellePharm Investigative Site
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Pierre-Bénite, France, 69310
    • PellePharm Investigative Site
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Munich, Germany, 80337
    • Klinik und Poliklinik für Dermatologie und Allergologie
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Tübingen, Germany, 72076
    • Universitäts Hautklinik
• Italy
  • Napoli, Italy, 80131
    • Ospedale Vanvitelli-University della Campania-Dermatologia Edificio 9
  • Roma, Italy, 00168
    • Catholic University of the Sacred Heart
  • Rozzano, Italy, 20089
    • Humanitas University Milan
  • Vicenza, Italy, 36100
    • Ospedale San Bortolo
• Netherlands
  • Maastricht, Netherlands, 6202
    • Maastricht University Medical Center - Dept of Dermatology
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Sevilla, Spain, 41009
    • Hospital Universitiario Virgen de la Macarena
• United Kingdom
  • Glasgow, United Kingdom, G38SJ
    • NHS Greater Glasgow and Clyde
  • London, United Kingdom, E1 1BB
    • Royal London Hospital
  • Oxford, United Kingdom, OX37LE
    • Oxford University Hospitals NHS Foundation Trust
  • Salford, United Kingdom, M68HD
    • Salford Royal Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinical Cancer Center
  • California
    • Newport Beach, California, United States, 92660
      • Dermatology Center of Newport
    • Redwood City, California, United States, 94063
      • Stanford University, Department of Dermatology
    • San Francisco, California, United States, 94115
      • University of California, San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Ormond Beach, Florida, United States, 32174
      • Leavitt Medical Associates of Florida
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Laser & Skin Surgery Center of Indiana
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5314
      • University of Michigan, Dept of Dermatology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, Department of Dermatology
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University Dermatology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Murray, Utah, United States, 84107
      • University of Utah MidValley Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The participant must be age at least 18 years of age at the Screening Visit.
2. The participant must provide written informed consent prior to any study procedures.

3. The participant must meet diagnostic criteria for the basal cell nevus (Gorlin) syndrome including major criterion #3a plus 1 additional major criterion or plus 2 additional minor criteria listed below.

   Major criteria:

   1. >2 histologically confirmed BCCs or 1 for participant under age 20.
   2. Odontogenic keratocysts of the jaw confirmed histologically.
   3. ≥3 palmar and/or plantar pits seen at the Screening Visit.
   4. Bilamellar calcification of the falx cerebri present at less than 20 years of age.
   5. Fused, bifid, or markedly splayed ribs.
   6. First degree relative with Gorlin syndrome.
   7. Patched protein 1 (PTCH1) mutation predicted to be of functional significance in normal tissue.

   Minor criteria:

   1. Macrocephaly.
   2. Congenital malformations including frontal bossing, cleft lip or palate, "coarse face", moderate to severe hypertelorism.
   3. Skeletal abnormalities detectable clinically: Sprengel deformity, marked pectus deformity, or marked finger syndactyly.
   4. Skeletal abnormalities detectable radiographically: bridging of the sella turcica; vertebral abnormalities such as hemivertebrae, fusion or elongation of the vertebral bodies; modeling defects of the hands and feet; flame shaped lucencies of the hands or feet.
   5. Ovarian fibroma.
   6. Medulloblastoma (Modification of criteria of V Kimonis et al Am J Med Genet 69: 299-308, 1997).
4. The participant must have 10 (with at least 3 on the face) clinically typical BCCs present within 24 months prior to Randomization (Baseline/Day 1). Additionally, the subject must have at least 2 BCCs with longest diameter <5 mm present on the face prior to Randomization (Baseline/Day 1).
5. The participant is willing to have blood collected to measure circulating drug levels.
6. The participant is willing to abstain from application of a non-study topical medication (prescription or over the counter) to facial skin for the duration of the trial except as prescribed by the Investigator. Moisturizers and emollients are allowed. Participant will be encouraged to use their preferred sunscreen with a sun protector factor (SPF) of at least 30 daily on all exposed skin sites.
7. If the participant is a woman of childbearing potential (WOCBP), she must be willing to use complete abstinence from sexual intercourse and/or she and her partner must be willing to use at least 2 highly-effective forms of birth control starting prior to Baseline, through the duration of the study, and for 12 months after last application of IP.
8. If the participant is a male with a female sex partner who is a WOCBP, the participant must be willing to use condoms, even after a vasectomy, starting prior to Baseline, through the duration of the study, and for at least 8 months after the last application of IP.
9. The participant is willing for all facial BCCs to be evaluated and treatment recommendations made only by the Investigator.
10. The participant is willing to forego treatment of facial BCCs with anything other than the study IP except when the Investigator believes that delay of treatment of a facial BCC potentially might compromise the health of the subject. During the trial the only allowed form of treatment is surgical. Non-facial BCCs may be removed at the discretion of the Investigator or Primary Skin Care Physician (PSCP).

Exclusion Criteria:

1. The subject has previously participated in a clinical trial evaluating patidegib topical gel.

2. The participant has used topical treatment to the face or systemic therapies that might interfere with the evaluation of the study IP. Among these are use of the following:

   1. 5-fluorouracil, imiquimod, diclofenac, or Ingenol mebutate (except as topical treatment to discrete non-facial BCCs) systemically or topically to the skin within the 2 months prior to the Screening Visit.
   2. Systemic chemotherapy within 1 year prior to the Screening Visit.
   3. Known inhibitors of the Hedgehog signaling pathway (such as vismodegib, sonidegib, itraconazole) topically or systemically within 3 months prior to the Screening Visit.
   4. Photodynamic therapy (PDT) except to localized non-facial, individual BCCs within 2 months prior to the Screening Visit.
3. The participant is known to have a hypersensitivity to any of the ingredients in the study medication formulation.
4. The participant is unable or unwilling to make a good faith effort to return to the study site for all study visits and tests.
5. The participant has uncontrolled systemic disease.
6. The participant has been treated for invasive cancer within the past 5 years excluding non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or chronic lymphocytic leukemia (CLL) Stage 0.
7. The participant has current, recent (within five half-lives of the experimental drug or if half-life not known, within the past 6 months prior to the Screening Visit), or planned participation in an experimental drug study while enrolled in this study.
8. The participant is a WOCBP who is unwilling or unable to comply with pregnancy prevention measures.
9. The participant is pregnant or breastfeeding.
10. The participant 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 may include a history of other skin conditions (such as severe facial eczema) 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 participant at high risk from treatment complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patidegib Topical Gel, 2%,; Participants will be randomized to receive Patidegib Topical Gel, 2%. The Patidegib Topical Gel, 2% will be dispensed to participants at each study visit and applied topically twice daily to the face.	Drug: Patidegib Topical Gel, 2%; Patidegib Topical Gel, 2%; Other Names: IP
Placebo Comparator: Patidegib Topical Gel, Vehicle; Participants will be randomized to receive Vehicle. The Patidegib Topical Gel, Vehicle will be dispensed to participants at each study visit and applied topically twice daily to the face.	Drug: Patidegib Topical Gel, Vehicle; Patidegib Topical Gel, Vehicle; Other Names: IP, Vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of new BCCs per participant	Baseline, Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of new surgically eligible BCCs (nSEBs) per participant	Month 12
Percentage of participants developing >=2 facial new BCCs	Month 12
Percentage of participants developing >=1 facial new BCCs	Month 12
Number of new BCCs per participant	Month 9
Number of new BCCs per participant	Month 6
Change in Advanced Basal Cell Carcinoma Index (aBCCdex) Lesion Symptom Score scale score	Baseline, Month 12

Collaborators and Investigators

• Sponsor: PellePharm, Inc.
• Investigators: Study Director: VP, Clinical Operations, PellePharm, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2019
• Primary Completion (Actual): December 28, 2020
• Study Completion (Actual): December 28, 2020

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Basal cell carcinoma; Hedgehog; Gorlin syndrome; Nevoid basal cell carcinoma syndrome; Basal cell nevus syndrome BCNS; Surgically eligible basal cell carcinomas; Patidegib
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease; Cysts; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Stomatognathic Diseases; Bone Diseases; Neoplastic Syndromes, Hereditary; Nevi and Melanomas; Jaw Diseases; Abnormalities, Multiple; Bone Diseases, Developmental; Odontogenic Cysts; Jaw Cysts; Bone Cysts; Neoplasms, Basal Cell; Syndrome; Carcinoma; Nevus; Basal Cell Nevus Syndrome; Nevus, Pigmented; Carcinoma, Basal Cell; Antihypertensive Agents; Veratrum Alkaloids
• Other Study ID Numbers: Pelle-926-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No