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.

Study Overview

• Status: Completed
• Conditions: Neurofibromatosis 1; Cutaneous Neurofibroma
• Intervention / Treatment: Drug: NFX-179 gel; Drug: Vehicle gel

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-7199
      • University of Arkansas for Medical Sciences
    • Rogers, Arkansas, United States, 72758
      • Northwest Arkansas Clinical Trials Center, PLLC
  • California
    • Fremont, California, United States, 94538
      • Center For Dermatology Clinical Research, Inc.
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • San Diego, California, United States, 92123
      • University Clinical Trials, Inc.
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Illinois
    • Evanston, Illinois, United States, 60077
      • Northshore University Healthsystem
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • New Brighton, Minnesota, United States, 55112
      • Minnesota Clinical Study Center
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Skin Specialists, P.C.
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group, LLC
    • Rochester, New York, United States, 14623
      • Skin Search of Rochester, Inc.
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest School of Medicine
  • Ohio
    • Mayfield Heights, Ohio, United States, 44124
      • Apex Clinical Research Center, LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Sugarloaf, Pennsylvania, United States, 18249
      • Derm Dox Center for Dermatology
  • Texas
    • Dallas, Texas, United States, 75230
      • Dermatology Treatment and Research Center
    • Houston, Texas, United States, 77030
      • UTHealth McGovern Medical School
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • The Education & Research Foundation, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NFX-179 Topical Gel 0.5%; NFX-179 topical gel 0.5% will be applied once daily to the target cutaneous neurofibromas (cNFs) for 182 days.	Drug: NFX-179 gel; NFX-179 topical gel is the active investigational product being studied; Other Names: NFX-179 topical gel
Experimental: NFX-179 Topical Gel 1.5%; NFX-179 topical gel 1.5% will be applied once daily to the target cNFs for 182 days.	Drug: NFX-179 gel; NFX-179 topical gel is the active investigational product being studied; Other Names: NFX-179 topical gel
Placebo Comparator: NFX-179 Topical Gel Vehicle; NFX-179 topical gel vehicle will be applied once daily to the target cNFs for 182 days.	Drug: Vehicle gel; NFX-179 vehicle gel is the placebo comparator for this study; Other Names: NFX-179 vehicle gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an event that occurred or worsened on or after the first dose of study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Baseline (Day 1) up to Day 211
Percentage of Participants With At Least 50% of Target Lesions With 50% Reduction in cNF Volume Above the Surrounding Non-tumor Skin	Treatment effectiveness was measured by the percentage of treated participants with at least 50% of target lesions with 50% reduction in cNF volume after 6 months of treatment. Tumor dimensions were measured using a standardized ruler.	Day 182

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With At Least 50% of Target Lesions With 50% Reduction in cNF Height Above the Surrounding Non-tumor Skin	Treatment effectiveness was measured by the percentage of treated participants with at least 50% of target lesions with 50% reduction in cNF height after 6 months of treatment. Tumor dimensions were measured using a standardized ruler.	Day 182
Mean Percent Change From Baseline in cNF Volume at Day 182 Based on cNF Volume Derived From Ruler Measurements	Mean percent change of tumor volume was calculated from ruler measurements throughout the course of treatment. Presented here are data analyzed at the participant level.	Baseline, Day 182
Change From Baseline in Tumor Severity Score Per Physician's Tumor Assessment (PTA) at Day 182	Effect of treatment with the PTA was the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The PTA is a 5-point measuring tumor severity (0 = clear/none, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe). Presented here are data analyzed at the participant level.	Baseline, Day 182
Change From Baseline in Tumor Severity Score Per Subject's Self-Assessment (SSA) at Day 182	The SSA was the participant's assessment of the average overall severity of each Target cNF at a particular time point. The SSA is a 5-point measuring tumor severity (0 = clear/none, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe).	Baseline, Day 182

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Outcome Measure to assess Target cNF symptoms over 182 days	This assessment is performed via the subject's assessment of their experience over the previous week with 9 items for each Target cNF (sensitivity, pain, itch, noticeability, size, appearance, care to avoid irritation, how much the cNF bothers the subject, self-consciousness). Each item is assessed by using a 5-point scale.	182 days

Collaborators and Investigators

• Sponsor: NFlection Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2021
• Primary Completion (Actual): October 2, 2023
• Study Completion (Actual): October 2, 2023

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Neurofibroma; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurofibromatoses; Neurofibromatosis 1
• Other Study ID Numbers: NFX-179-NF1-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No