NFX-179 Topical Gel Treatment for Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF)

A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2 Dose-Response Study to Determine Safety and Effectiveness of Two Concentrations of NFX-179 Gel in Subjects With Cutaneous Neurofibromas

This is a randomized, double-blind, vehicle-controlled, parallel group dose response study evaluating the safety and effectiveness of 2 concentrations of NFX-179 gel in participants with cNF. At Visit 1 (Screening visit), the investigator will identify 10 Target cNFs that fulfil the enrollment criteria. The Target cNFs must be located on the participant's face, anterior trunk, or upper extremities. Two Target cNFs must be on the face and 8 must be on the anterior trunk or upper extremities. The study medication will be applied topically once daily to the Target cNFs for 182 days (26 weeks). During the duration of the study participants will be evaluated for safety and efficacy.

Inclusion Criteria:

1. Participant is at least 18 years of age

2. Participant must provide written informed consent prior to any study procedures

3. Participant must have a clinical diagnosis of NF1

4. Participant has 10 clinically diagnosed Target cNFs with preferably 2 Target cNFs located on the face and 8 Target cNFs located on the anterior trunk or upper extremities. Alternatively, at least 1 Target cNF is located on the face, in which case 9 Target cNFs must be located on the anterior trunk or upper extremities. Each Target cNF must meet the following criteria:

   • Has, in the investigator's opinion, a clinically typical appearance
   • Is not within 1 centimeter (cm) of the orbital rim
   • Is not covered with hair that might, in the investigator's opinion, interfere with obtaining photographs or impair evaluation of the cNF
   • Has a Physician's Tumor Assessment grade ≥2
   • Is dome shaped
   • Is not pedunculated
   • Is a discrete cNF surrounded by sufficient non-affected skin that, in the investigator's opinion:
   • The dimensions can be measured
   • The perimeter can be outlined in the study photographs
   • Is not irritated (or example, bleeding, inflamed)
   • Is not in an area participant to repeated trauma (or example, area that is shaved, on the beltline, under a bra strap, etc.)
   • Does not have an active cutaneous infection
   • Target cNFs on the face must have the following tumor dimensions:
   • Has a length that is ≥5 millimeters (mm) and ≤14 mm
   • Has a width that is ≥5 mm and ≤14 mm
   • Has a height that is ≥2 mm.
   • Target cNFs on the anterior trunk or upper extremities must have the following tumor dimensions:
   • Has a length that is ≥ 7mm and ≤14 mm
   • Has a width that is ≥5 mm and ≤14 mm
   • Has a height that is ≥2 mm.

5. Participant agrees to avoid exposure of Target cNFs to excessive sunlight and to use her/his routine sunscreen if excessive exposure cannot be avoided

6. Participant agrees not to use tanning beds

7. Participant is willing to forego treatment of each Target cNF, except protocol specified therapy, during the study

8. Female participants who are women of childbearing potential must have a negative urine pregnancy test result and be willing to use a protocol approved, contraceptive method for the duration of the study

9. Participant is willing and able to follow all study instructions and to attend all study visits.

Exclusion Criteria:

1. Participant has used any of the following topical therapies within the specified period prior to Visit 1 (screening visit) on or in proximity to any Target cNF that, in the investigator's opinion, impairs evaluation of any the cNFs or which exposes the participant to an unacceptable risk by study participation:

   • Corticosteroids; 30 days
   • Prescription retinoids (for example, tazarotene, tretinoin, adapalene); 30 days
   • > 5% of an alpha-hydroxy acid (for example, glycolic acid, lactic acid); 30 days
   • Fluorouracil; 30 days
   • Imiquimod; 30 days
   • LASER, light (for example, intense pulsed light [IPL], photo-dynamic therapy [PDT]) or other energy-based therapy; 180 days
   • Mitogen-activated protein kinase (MEK) inhibitor or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) inhibitor; ever.

2. The participant has used any of the following systemic medications therapies within the specified period prior to Visit 1 (screening visit):

   • Retinoids (for example, etretinate, isotretinoin); 90 days
   • MEK inhibitors; 180 days
   • BRAF inhibitors; 180 days

3. Participant has a history of hypersensitivity to any of the ingredients in the study medications

4. Participant has any known intercurrent illness or physical condition that would, in the investigator's opinion, impair evaluation of a Target cNF or which exposes the participant to an unacceptable risk by study participation

5. Participant has, in the investigator's opinion, clinically relevant history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis

6. Participant has a history of metastatic disease, or active cancer (excluding nonmelanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the breast, or Stage 0 chronic lymphocytic lymphoma) within the previous 5 years

7. Participant has any condition (for example, other skin conditions or diseases, metabolic dysfunction, physical examination findings, clinical laboratory findings) or situation (for example, vacation, scheduled surgery) that would, in the investigator's opinion, impair evaluation of a Target cNF or which exposes the participant to an unacceptable risk by study participation

8. Participant has participated in an investigational drug trial in which administration of an investigational study medication occurred within the previous 30 days