This Study is to Evaluate the Safety and Pharmacokinetics of SBS-101 in Patients With Oral Premalignant Lesions

• ClinicalTrials.gov Identifier: NCT03939364
• Recruitment Status: Withdrawn
• First Posted: May 6, 2019
• Last Update Posted: October 19, 2021
• Sponsor: Skyline Biosciences
• Information provided by (Responsible Party): Skyline Biosciences

Tracking Information

• First Submitted Date: April 18, 2019
• First Posted Date: May 6, 2019
• Last Update Posted Date: October 19, 2021
• Estimated Study Start Date: January 2022
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 3, 2019)

• Percentages of patients with overall response will be summarized by treatment [ Time Frame: 13 weeks ]
  Overall response is defined as complete or partial response in either clinical or histological outcome without worsening of either.
• The percentages of patients reporting any treatment-emergent adverse event (AE) will be tabulated by system organ class and preferred term for each treatment [ Time Frame: 13 weeks ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: May 3, 2019): Plasma concentrations of isotretinoin will be summarized by treatment using descriptive statistics [ Time Frame: 13 weeks ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: This Study is to Evaluate the Safety and Pharmacokinetics of SBS-101 in Patients With Oral Premalignant Lesions
• Official Title: A Phase 1, Randomized, Double-blind, Placebo Controlled, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of SBS-101 After Intraoral Application in Patients With Oral Premalignant Lesions (OPL)
• Brief Summary: This study will be the first study investigating the safety, pharmacokinetics (PK), and efficacy of SBS-101 on oral pre-malignant lesions. As such, no clinical data has yet been generated using SBS-101 oral adhesive film.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Other
• Condition: Leukoplakia, Oral

Intervention

• Drug: SBS-101
  Isotretinoin Oral-Adhesive Film
• Drug: Placebo
  Placebo

Study Arms

• Experimental: 0.1% SBS-101
  Intervention: Drug: SBS-101
• Experimental: 0.3% SBS-101
  Intervention: Drug: SBS-101
• Experimental: 0.2% SBS-101
  Intervention: Drug: SBS-101
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: October 11, 2021): 0
• Original Estimated Enrollment (submitted: May 3, 2019): 24
• Estimated Study Completion Date: May 2023
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patient is able to comprehend and willing to sign an Informed Consent Form.
2. Patient is willing and able to follow all study instructions and to attend all study visits
3. Patient is male or female aged 18 years or older at Screening.
4. Patient has oral leukoplakia or erythroplakia at least 5mm in length on its longest axis with histopathology showing mild, moderate, or severe dysplasia (index lesion histology score of ≥2) with incisional (punch) biopsy at Screening (or within 30 days prior to Screening).
5. Patient agrees to not use any topical therapies (i.e. use of over the counter and medically prescribed topical creams, ointments, or oral rinses) on the index lesion other than the study drug that, in the Investigator's opinion, might influence the status of the index lesion for the duration of the study.
6. Patient agrees to not apply any other topical products or use potential irritants (i.e. alcohol containing mouthwash) to the oral premalignant lesions throughout the study. Note: mouthwash that includes non-alcohol containing formulations of Listerine and Crest is acceptable to use during the study.
7. If female, patient is non-pregnant, non-lactating and is not planning for pregnancy during the study period or for 1 month after the last dose of study drug.

8. Female patients of non-childbearing potential must meet the following requirements:

   1. Pre-menopausal with documentation of surgical sterilization (i.e., hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or bilateral salpingectomy) at least 3 months prior to study entry.
   2. Post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with follicle-stimulating hormone (FSH) level ≥40 milli-international units per milliliter (mIU/mL) at Screening.

9. Female patients of child-bearing potential must select and commit to use 2 forms of effective contraception simultaneously, at least 1 of which must be a primary form, unless absolute abstinence is the chosen method, or the patient has undergone a hysterectomy. Patients must use 2 forms of effective contraception at least 1 month prior to study initiation (Screening), during the study, and for 1 month after the final dose of study drug.

   Primary (hormonal or surgical)

   1. Tubal ligation
   2. Partner's vasectomy
   3. Intrauterine devices
   4. Birth control pills
   5. Injectable/implantable/insertable hormonal birth control products Secondary (Barrier Method)
   1. Diaphragm (with spermicide)
   2. Cervical cap (with spermicide)
   3. Male condom (with spermicide)

10. Male patients must agree to use condoms during sexual intercourse during the study and for 3 months after the final dose of study drug. If a female partner is of childbearing potential, she should use contraception as detailed in Inclusion criterion

    # 9. Males must also agree to not donate sperm from the time of first dosing and for 3 months after the final dose of study drug.

11. Patient's Eastern Cooperative Oncology Group (ECOG) performance status grade is 0 or 1 at Screening.
12. Patient's organ function is determined to be adequate based on laboratory testing at Screening (e.g. Hemoglobin levels ≥ 10g/dl; White Blood Cells (WBC) ≥ 3,000/μL; Platelets ≥ 100,000/μL; Total bilirubin ≤ 1.5x Upper Limit of Normal (ULN); Aspartate Aminotransferase (AST)/ Alanine aminotransferase (ALT) < 2x Upper Limit of Normal (ULN);, Blood urea nitrogen (BUN) & serum creatinine ≤ 1.5x Upper Limit of Normal (ULN); Lactate dehydrogenase (LDH) ≤ 1.5x Upper Limit of Normal (ULN); Glucose < 200 mg/dL; Thyroid Stimulating Hormone (TSH) ≤ 5.0 μU/mL; C-Reactive Protein < 5.0 mg/L).
13. Negative urine drug screen at Screening.
14. Patient is in good general health and free of any known disease state or physical condition which, in the Investigator's opinion, might impair evaluation of the oral premalignant lesions or which exposes the patient to an unacceptable risk by participating in the study.

Exclusion Criteria:

1. Patient has oral lesions to be treated that are infected (e.g. lesions that require local or systemic antimicrobial, antifungal, or antiviral therapy to treat an infection) within 14 days of Randomization.
2. Patients must not use any systemic (e.g., oral or injectable) corticosteroid therapy during the study or within 30 days prior to Screening. However, use of topical, inhaled, ophthalmic, intraarticular and intralesional steroids is permitted.
3. Patient has used any topical or systemic chemotherapeutic product within 30 days prior to Randomization.
4. Use of smokeless tobacco within 4 weeks prior to Screening or during the course of the study.
5. Patient has been diagnosed with hairy leukoplakia.
6. Patient has evidence of a systemic infection or has used systemic antibiotics within 14 days prior to start of dosing for males and females of non-childbearing potential or within 30 days prior to start of dosing for Women of Childbearing Potential (WOCBP).
7. Patient is currently taking high doses of vitamin A (> 25,000 USP units per day) or has previously used isotretinoin for the treatment of another condition within 6 months of Screening.
8. Patient is currently taking phenytoin or other prohibited medication
9. Patient's index lesion is a recurrent dysplastic lesion in a previously treated area for oral cancer (previous treatment, bed/excision, etc.).
10. The patient has received radiation or chemoradiation therapy to oral cavity within 2 years of Randomization.
11. The patient has any immune compromising conditions at Screening (i.e. HIV, SLE, etc.) or has been treated with immunomodulating medications within 6 months of Screening.
12. Patient currently has poorly controlled diabetes mellitus (uninterrupted hemoglobin A1c >9% for ≥1 year despite standard care).
13. Patient has a history of cardiac, hepatic (ALT and or AST >2x ULN, Total bilirubin >1.5x ULN at Visit 1), or renal disease (eGFR<45 ml/min/1.73 m2) that, in the opinion of the Investigator, might put the patient at undue risk by participating in the study or interferes with the study drug application or the study assessments.
14. Patient has a history of sensitivity to any of the active ingredients in the study drug (e.g. isotretinoin, propylene glycol, natural mint), or retinoids, or vitamin A.
15. Patient has used oral isotretinoin within 14 days of Screening. Patients must agree to abstain from using oral isotretinoin throughout the duration in the study.
16. Patient has participated in an investigational drug trial in which administration of an investigational study drug occurred within 30 days prior to Randomization.
17. Patient is, in the opinion of the Investigator, not an appropriate candidate for study participation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03939364
• Other Study ID Numbers: SBS-101-CL-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Skyline Biosciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Skyline Biosciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Joy Schleyer; Skyline Biosciences

• PRS Account: Skyline Biosciences
• Verification Date: October 2021