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

Phase 2
Completed
Conditions
Neurofibromatosis 1
Cutaneous Neurofibroma
Interventions
Drug: NFX-179 gel
Drug: Vehicle gel
Registration Number
NCT05005845
Lead Sponsor
NFlection Therapeutics, Inc.
Brief Summary

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 subjects with cutaneous neurofibromas. At Visit 1, the investigator will identify 10 Target cNFs that fulfil the enrollment criteria. The Target cNFs must be located on the subject'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 QD to the Target cNFs for 182days (26 weeks). During the duration of the study subjects will be evaluated for safety and efficacy.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
199
Inclusion Criteria
  1. Subject is at least 18 years of age

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

  3. Subject must have a clinical diagnosis of NF1

  4. Subject 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 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 (e.g., bleeding, inflamed)
    • Is not in an area subject to repeated trauma (e.g., 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 ≥5mm and ≤14mm
    • Has a width that is ≥5mm and ≤14mm
    • Has a height that is ≥2mm.
    • Target cNFs on the anterior trunk or upper extremities must have the following tumor dimensions:
    • Has a length that is ≥7mm and ≤14mm
    • Has a width that is ≥5mm and ≤14mm
    • Has a height that is ≥2mm.
  5. Subject agrees to avoid exposure of Target cNFs to excessive sunlight and to use her/his routine sunscreen if excessive exposure cannot be avoided

  6. Subject agrees NOT to use tanning beds

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

  8. Female subjects 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. Subject is willing and able to follow all study instructions and to attend all study visits.

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

    • Corticosteroids; 30 days
    • Prescription retinoids (e.g., tazarotene, tretinoin, adapalene); 30 days
    • > 5% of an alpha-hydroxy acid (e.g., glycolic acid, lactic acid); 30 days
    • Fluorouracil; 30 days
    • Imiquimod; 30 days
    • LASER, light (e.g., intense pulsed light [IPL], photo-dynamic therapy [PDT]) or other energy-based therapy; 180 days
    • MEK inhibitor or BRAF inhibitor; ever.
  2. The subject has used any of the following systemic medications therapies within the specified period prior to Visit 1:

    • Retinoids (e.g., etretinate, isotretinoin); 90 days
    • MEK inhibitors; 180 days
    • BRAF inhibitors; 180 days
  3. Subject has a history of hypersensitivity to any of the ingredients in the study medications

  4. Subject 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 subject to an unacceptable risk by study participation

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

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

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
0.5% NFX-179 gelNFX-179 gelTopical gel applied once daily to target cNFs
Vehicle gelVehicle gelTopical gel applied once daily to target cNFs
1.5% NFX-179 gelNFX-179 gelTopical gel applied once daily to target cNFs
Primary Outcome Measures
NameTimeMethod
Safety and effectiveness of once daily NFX-179 gel treatment for 182 days measured by local tolerability assessments, safety laboratory tests, and target cNF volume reduction182 days

Safety will be measured by routine safety laboratory tests (CBC/differential, serum chemistry, urinalysis), and local tolerability assessment where the investigator will assess erythema, edema, scabbing/crusting, vesiculation, and erosion. The subject will assess stinging, burning, and pruritus. All assessments are performed using a 4-point scale (0 none, 1 mild, 2 moderate, 3 severe). Effectiveness will be measured by the percent of treated subjects with at least a 50% reduction in cNF volume after 6 months of treatment.

Safety of once daily NFX-179 gel treatment for 182 days by adverse events and serious adverse events assessments182 days

Safety of NFX-179 gel compared to the vehicle group will be measured by the assessment and occurrence of new and ongoing adverse events (AEs)/serious adverse events (SAEs).

Secondary Outcome Measures
NameTimeMethod
Percent change in cNF volume over 182 days182 days

Percent change of tumor volume will be calculated through ruler measurements and two-dimensional photography throughout the course of treatment. All modes of tumor volume measurement are reported in cubic millimeters.

Percent of subjects with at least 50% Target cNF volume reduction after 182 days182 days

Treatment effectiveness will be measured by the percent of treated subjects with at least a 50% reduction in cNF volume after 6 months of treatment. Tumor volume will be measured by ruler measurements and two-dimensional photography. All modes of tumor volume measurement are reported in cubic millimeters.

Physician's Tumor Assessment of Target cNF severity over 182 days182 days

Effect of treatment with The Physician Tumor Assessment is the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The Physician Tumor Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). This assessment is performed at Screening, Baseline/Day 1, Days 58, 183, and 211.

Subject's Self-Assessment of Target cNF severity over 182 days182 days

The Subject Self-Assessment is the subject's assessment of the average overall severity of each Target cNF at a particular time point and is not a comparison with any other time point. The Subject Self-Assessment is a 5-point measuring tumor severity (0 clear/none, 1 almost clear, 2 mild, 3 moderate, 4 severe). This assessment is performed at Screening, Baseline/Day 1, Days 58, 183, and 211.

Trial Locations

Locations (23)

The Johns Hopkins School of Medicine

🇺🇸

Baltimore, Maryland, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Minnesota Clinical Study Center

🇺🇸

New Brighton, Minnesota, United States

Dermatology Treatment and Research Center

🇺🇸

Dallas, Texas, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Children's National Hospital

🇺🇸

Washington, District of Columbia, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Northwest Arkansas Clinical Trials Center, PLLC

🇺🇸

Rogers, Arkansas, United States

Center for Dermatology Clinical Research, Inc.

🇺🇸

Fremont, California, United States

Northshore University HealthSystem

🇺🇸

Evanston, Illinois, United States

Dawes Fretzin Clinical Research Group

🇺🇸

Indianapolis, Indiana, United States

Sadick Research Group, LLC

🇺🇸

New York, New York, United States

Skin Search of Rochester, Inc.

🇺🇸

Rochester, New York, United States

Apex Clinical Research Center, LLC

🇺🇸

Mayfield Heights, Ohio, United States

UTHealth McGovern Medical School

🇺🇸

Houston, Texas, United States

Derm Dox Center for Dermatology

🇺🇸

Sugarloaf, Pennsylvania, United States

The Education & Research Foundation, Inc.

🇺🇸

Lynchburg, Virginia, United States

University Clinical Trials, Inc.

🇺🇸

San Diego, California, United States

Skin Specialists, P.C.

🇺🇸

Omaha, Nebraska, United States

Wake Forest School of Medicine

🇺🇸

Winston-Salem, North Carolina, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

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