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)

Basal Cell Nevus Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03703310
• Other study ID #: Pelle-926-301
• Status: Completed
• Phase: Phase 3
• Start date: February 19, 2019
• Est. completion date: December 28, 2020

Study information

• Verified date: March 2021
• Source: PellePharm, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: December 28, 2020
• Est. primary completion date: December 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Basal Cell Nevus Syndrome
• Carcinoma
• Carcinoma, Basal Cell
• Nevus
• Nevus, Pigmented
• Syndrome

Intervention

Drug:
• Patidegib Topical Gel, 2%
Patidegib Topical Gel, 2%
• Patidegib Topical Gel, Vehicle
Patidegib Topical Gel, Vehicle

Locations

Country	Name	City	State
Belgium	PellePharm Investigative Site	Brussels
Belgium	PellePharm Investigative Site	Leuven
Canada	Pellepharm Investigative Site	Toronto
Canada	Clinical Trials Unit - The Skin Care Centre	Vancouver	British Columbia
Denmark	PellePharm Investigative Site	Copenhagen
France	Hopital Saint-Andre - CHU Bordeaux	Bordeaux Cedex
France	CHRU de Lille - Hopital Claude HURIEZ	Lille Cedex
France	CHU La Timone	Marseille
France	PellePharm Investigative Site	Nantes
France	Hopital Saint-Louis	Paris
France	PellePharm Investigative Site	Pierre-Bénite
Germany	Charite - Universitatsmedizin Berlin	Berlin
Germany	Klinik und Poliklinik fur Dermatologie und Allergologie	Munich
Germany	Universitatsklinikum Münster	Münster
Germany	Universitats Hautklinik	Tübingen
Italy	Ospedale Vanvitelli-University della Campania-Dermatologia Edificio 9	Napoli
Italy	Catholic University of the Sacred Heart	Roma
Italy	Humanitas University Milan	Rozzano
Italy	Ospedale San Bortolo	Vicenza
Netherlands	Maastricht University Medical Center - Dept of Dermatology	Maastricht
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitiario Virgen de la Macarena	Sevilla
United Kingdom	NHS Greater Glasgow and Clyde	Glasgow
United Kingdom	Royal London Hospital	London
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United Kingdom	Salford Royal Hospital	Salford
United States	University of Michigan, Dept of Dermatology	Ann Arbor	Michigan
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Laser & Skin Surgery Center of Indiana	Carmel	Indiana
United States	The University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Duke University	Durham	North Carolina
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	MD Anderson Cancer Center	Houston	Texas
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	University of Minnesota, Department of Dermatology	Minneapolis	Minnesota
United States	University of Utah Midvalley Dermatology	Murray	Utah
United States	Yale School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Dermatology Center of Newport	Newport Beach	California
United States	Leavitt Medical Associates of Florida	Ormond Beach	Florida
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinical Cancer Center	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Stanford University, Department of Dermatology	Redwood City	California
United States	Saint Louis University Dermatology	Saint Louis	Missouri
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
PellePharm, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

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