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

• Sponsor: PellePharm, Inc.
• Information provided by (Responsible Party): PellePharm, Inc.

Study Description

Brief 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 Basal Cell Nevus Syndrome (BCNS; Gorlin Syndrome). Subjects 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 surgically eligible BCCs (nSEBs) that develop over the 12 month period.

Condition or disease	Intervention/treatment	Phase
Basal Cell Nevus Syndrome	Drug: Patidegib Topical Gel, 2%; Drug: Patidegib Topical Gel, Vehicle	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Partcipants will be randomized 1:1 to receive Patidegib Topical Gel, 2%, or Vehicle (IP)
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:	As a double-blinded study, the Investigators, the site staff, Sponsor, and the Clinical Monitor(s) will be blinded to the treatment assigned to individual participants.
Primary Purpose:	Treatment
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
Actual Study Start Date :	February 20, 2019
Estimated Primary Completion Date :	May 1, 2020
Estimated Study Completion Date :	May 1, 2020

Arms and Interventions

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 Name: 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 Name: IP, Vehicle

Outcome Measures

Primary Outcome Measures :

1. Number of new surgically eligible BCCs (nSEBs) [ Time Frame: Month 12 ]

Secondary Outcome Measures :

1. Percentage of participants developing >=2 facial nSEBs [ Time Frame: Baseline, Month 12 ]
2. Percentage of participants developing >=1 facial nSEBs [ Time Frame: Baseline, Month 12 ]
3. Number of nSEBs per participant [ Time Frame: Month 9 ]
4. Number of nSEBs per participant [ Time Frame: Month 6 ]
5. Number of new BCCs [ Time Frame: Baseline, Month 12 ]
6. Change in Advanced Basal Cell Carcinoma Index (aBCCdex) lesion score [ Time Frame: Baseline, Month 12 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 BCNS.
   7. Patched proteine 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 an 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. Topical glucocorticoids of potency greater than 2.5% hydrocortisone or desonide within the 30 days prior to the Screening Visit.
   2. Retinoids (such as etretinate, isotretinoin, acetretin, tazarotene, tretinoic acid, adapalene) systemically or topically, or >5% concentration of an alpha hydroxy acid (such as glycolic acid, lactic acid) within the 3 months prior to the Screening Visit.
   3. 5-fluorouracil, imiquimod, diclofenac, or Ingenol mebutate (except as topical treatment to discrete non-facial BCCs) systemically or topically to the skin within the 3 months prior to the Screening Visit.
   4. Systemic chemotherapy within 1 year prior to the Screening Visit.
   5. Known inhibitors of the Hedgehog signaling pathway (such as vismodegib, sonidegib, itraconazole) topically or systemically within 3 months prior to the Screening Visit.
   6. Photodynamic therapy (PDT) except to localized non-facial, individual BCCs within 3 months prior to the Screening Visit.
   7. High-dose nicotinamide orally within 3 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.

Contacts and Locations

Contacts

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Contact: Sr. Clinical Operations Manager	844-332-5161	clinical@pellepharm.com

Locations

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United States, California
Dermatology Center of Newport	Recruiting
Newport Beach, California, United States, 92660
Contact clinical@pellepharm.com
Principal Investigator: Michelle Aszterbaum, MD
Stanford University, Department of Dermatology	Recruiting
Redwood City, California, United States, 94063
Contact: Julie Nguyen 650-723-3046 julietn@stanford.edu
Principal Investigator: Anne Lynn S Chang, MD
University of California, San Francisco	Recruiting
San Francisco, California, United States, 94115
Contact: Christine Aroyan 415-353-9684 christine.aroyan@ucsf.edu
Principal Investigator: Sarah Arron, MD, PhD
United States, Connecticut
Yale School of Medicine	Recruiting
New Haven, Connecticut, United States, 06519
Contact: Mahin Dawood, MS 203-785-5505 mahin.dawood@yale.edu
Principal Investigator: Sean Christensen, MD, PhD
United States, Florida
Leavitt Medical Associates of Florida	Recruiting
Ormond Beach, Florida, United States, 32174
Contact: Sandra Warrington 386-523-0768 sandra.warrington@leavittmgt.com
Principal Investigator: James Solomon, MD, PhD
United States, Illinois
The University of Chicago	Recruiting
Chicago, Illinois, United States, 60637
Contact: K. Yazmin Reyna Blanco 773-702-7696 kreynablanco@medicine.bsd.uchicago.edu
Principal Investigator: Diana Bolotin, MD
United States, Indiana
Laser & Skin Surgery Center of Indiana	Recruiting
Carmel, Indiana, United States, 46032
Contact: Jami Zenor 317-660-4862 research@thelassi.com
Principal Investigator: C. William Hanke, MD
United States, Minnesota
University of Minnesota, Department of Dermatology	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Irmina Wallander 612-624-5721 wall0396@umn.edu
Principal Investigator: Ian Maher, MD
United States, Missouri
Saint Louis University Dermatology	Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Rosemary King, PA-C 314-256-3436 rosemary.king@health.slu.edu
Principal Investigator: Patricia Missall, MD, PhD
United States, New York
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Grace Ulerio, CCRC 212-305-8444 gu2102@cumc.columbia.edu
Principal Investigator: David Bickers, MD
United States, North Carolina
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: Kim Scoggins 919-684-1380 kim.scoggins@duke.edu
Principal Investigator: Meenal Kheterpal, MD
United States, Oregon
Oregon Health and Science University	Recruiting
Portland, Oregon, United States, 97239
Contact: Christina Armstrong 503-494-6907 armstrch@ohsu.edu
Principal Investigator: Anna Bar, MD
United States, Pennsylvania
Penn State Health Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Amy Longenecker, BSN, RN 717-531-5136 alongenecker@pennstatehealth.psu.edu
Principal Investigator: Elizabeth Billingsley, MD
France
Hopital Saint-Andre - CHU Bordeaux	Recruiting
Bordeaux Cedex, France, 33075
Contact: Christine Alfaro 33 5 57 82 25 21 christine.alfaro@chu-bordeaux.fr
Principal Investigator: Pr Marie Beylot-Barry
CHRU de Lille - Hopital Claude HURIEZ	Recruiting
Lille Cedex, France, 59037
Contact: Benoit Minart 33 320446415 benoit.minart@chru-lille.fr
Principal Investigator: Pr. Laurent Mortier
CHU La Timone	Recruiting
Marseille, France, 13395
Contact: Elisabeth Vieu 33 4 91 38 49 30 elisabeth.vieu@ap-hm.fr
Principal Investigator: Pr Jean-Jacques Grob
PellePharm Investigative Site	Recruiting
Nantes, France, 44093
Contact clinical@pellepharm.com
Hopital Saint-Louis	Recruiting
Paris, France, 75010
Contact: Halim Bataouche +33 1 71 20 74 14 halim.bataouche@aphp.fr
Principal Investigator: Pr. Nicole Basset-Seguin
Netherlands
Maastricht University Medical Center - Dept of Dermatology	Recruiting
Maastricht, Netherlands, 6202
Contact: Robert-Jan Alers 31(0)43-387-7295 k.mosterd@mumc.nl
Principal Investigator: Klara Mosterd, MD
Spain
Hospital Clinic I Provincial	Recruiting
Barcelona, Spain, 08036
Contact: Pablo Iglesias Garcia 34 93 227 54 00 ext 3200-4622 pabloiglesiasgarcia@msn.com
Principal Investigator: Susana Puig, MD
Hospital Universitario Ramon y Cajal	Recruiting
Madrid, Spain, 28034
Contact: Oscar Munoz Moreno-Arrones 34 91 336 80 00 ext 7909 ommarrones@gmail.com
Principal Investigator: Luis Rios Buceta, MD

Sponsors and Collaborators

PellePharm, Inc.

Investigators

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Study Director:	VP, Clinical Operations	PellePharm, Inc.

More Information

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Responsible Party:	PellePharm, Inc.
ClinicalTrials.gov Identifier:	NCT03703310 History of Changes
Other Study ID Numbers:	Pelle-926-301
First Posted:	October 11, 2018
Last Update Posted:	May 15, 2019
Last Verified:	May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by PellePharm, Inc.:

Gorlin syndrome; Basal cell nevus syndrome BCNS; Nevoid basal cell carcinoma syndrome	Basal cell carcinoma; Hedgehog; Surgically eligible basal cell carcinomas

Additional relevant MeSH terms:

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Syndrome; Carcinoma; Carcinoma, Basal Cell; Nevus; Basal Cell Nevus Syndrome; Nevus, Pigmented; Disease; Pathologic Processes; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Basal Cell; Nevi and Melanomas; Odontogenic Cysts	Jaw Cysts; Bone Cysts; Cysts; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Genetic Diseases, Inborn; Veratrum Alkaloids; Antihypertensive Agents