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

NCT02762084 | Completed Phase 2 Results DMC

• 2 other identifiers: Pelle-926-2012015-004274-15
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Basal Cell Nevus Syndrome

Keywords

Gorlin Syndrome; Basal Cell; Nevus Syndrome; BCNS; nevoid basal cell carcinoma syndrome; Basal cell carcinoma; Hedgehog; Surgically Eligible Basal Cell Carcinomas

Outcome Measures

Primary Outcomes (4)

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

  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).

  Baseline, Week 26

• 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

  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.

  Baseline, Week 6

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

  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.

  Baseline through Week 26

• 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

  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.

  Baseline through Week 26

Secondary Outcomes (7)

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

  Baseline, Week 26

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

  Baseline, Week 26

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

  Baseline, Week 26

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

  Baseline and Weeks 6, 10, 14, 18, and 22

• Percent Change in Central Facial SEBs From Baseline

  Baseline and Weeks 6, 10, 14, 18, 22, and 26

Other Outcomes (1)

• Percentage of Treatment-targeted SEBs Achieving Clear or Almost Clear on the 5-point Investigator Static Global Tumor Assessment (ISGTA) Scale

  Baseline and Weeks 6, 10, 14, 18, 22, and 26

Study Arms (3)

Patidegib gel 2%

EXPERIMENTAL

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

Drug: Patidegib

Patidegib gel 4%

EXPERIMENTAL

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

Drug: Patidegib

Vehicle gel

PLACEBO COMPARATOR

Vehicle gel, applied topically, twice daily for 26 weeks

Drug: Vehicle gel

Interventions

Patidegib DRUG

Also known as: Study drug

Patidegib gel 2%; Patidegib gel 4%

Vehicle gel DRUG

Also known as: Placebo

Vehicle gel

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant is from 18 to 85 years of age, inclusive.
• The participant must provide written informed consent prior to any study procedures.
• The participant must meet diagnostic criteria for BCNS, including the first listed major criterion below plus one additional major criterion, or the first listed major criterion below plus 2 of the minor criteria outlined below:
• Major 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
• Patched 1 (PTCH1) gene mutation in normal tissue
• Minor Criteria:
• Macrocephaly
• 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

You may not qualify if:

• The participant 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 SMO, and the unknown level of systemic exposure following topical application in humans. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (that is, has had menses at any time in the preceding 24 consecutive months).
• The participant 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 (such as etretinate, isotretinoin, tazarotene, tretinoin, adapalene) systemically or topically or \> 5% of an alphahydroxy acid (such as glycolic acid, lactic acid) or 5-fluorouracil or imiquimod (except as topical treatment to discrete BCCs) systemically or topically to the skin during the 6 months prior to entry.
• 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 (such as vismodegib, patidegib, and sonidegib) topically or systemically within 6 months of entry into the study.
• The participant has a history of hypersensitivity to any of the ingredients in the study drug formulation.
• The participant is unable or unwilling to make a good faith effort to return for all follow-up visits and tests.
• The participant has uncontrolled systemic disease.
• The participant has clinically important history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis.
• The participant has any condition or situation which in the Investigator's opinion may put the participant at significant risk, could confound the study results, or could interfere significantly with the participant'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 participant at high risk from treatment complications.
• The participant has a history of invasive cancer within the past 5 years excluding non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of breast, or chronic lymphocytic lymphoma (Stage 0).
• The participant has current, recent (within 4 weeks of Baseline visit), or planned participation in an experimental drug study while enrolled in this study.
• Female sexual partner(s) of male participants who are unwilling or unable to comply with pregnancy prevention measures.

Sponsors & Collaborators

• PellePharm, Inc.: lead

Study Sites (2)

Royal London Hospital

London, United Kingdom

Location

Manchester Royal Infirmary

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Basal Cell Nevus Syndrome; Carcinoma, Basal Cell

Interventions

IPI-926; Drug Evaluation

Condition Hierarchy (Ancestors)

Odontogenic Cysts; Jaw Cysts; Bone Cysts; Cysts; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Basal Cell; Neoplastic Syndromes, Hereditary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Jaw Diseases; Stomatognathic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Results Point of Contact

• Title: Chief Medical Officer
• Organization: PellePharm, Inc.

Info@Pellepharm.com

(510) 502-6144

Study Officials

• John Lear, MD

  Manchester Royal Infirmary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: May 4, 2016
• Study Start: June 6, 2016
• Primary Completion: April 24, 2017
• Study Completion: April 24, 2017
• Last Updated: July 23, 2020
• Results First Posted: July 15, 2019

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)