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

Neurofibromatosis 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05005845
• Other study ID #: NFX-179-NF1-202
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2021
• Est. completion date: October 4, 2023

Study information

• Verified date: November 2023
• Source: NFlection Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: October 4, 2023
• Est. primary completion date: October 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous Neurofibroma
• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1

Intervention

Drug:
• NFX-179 gel
NFX-179 topical gel is the active investigational product being studied
• Vehicle gel
NFX-179 vehicle gel is the placebo comparator for this study

Locations

Country	Name	City	State
United States	The Johns Hopkins School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Dermatology Treatment and Research Center	Dallas	Texas
United States	Northshore University HealthSystem	Evanston	Illinois
United States	Center for Dermatology Clinical Research, Inc.	Fremont	California
United States	University of Florida	Gainesville	Florida
United States	UTHealth McGovern Medical School	Houston	Texas
United States	Dawes Fretzin Clinical Research Group	Indianapolis	Indiana
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	The Education & Research Foundation, Inc.	Lynchburg	Virginia
United States	Apex Clinical Research Center, LLC	Mayfield Heights	Ohio
United States	Minnesota Clinical Study Center	New Brighton	Minnesota
United States	Sadick Research Group, LLC	New York	New York
United States	Skin Specialists, P.C.	Omaha	Nebraska
United States	Oregon Health & Science University	Portland	Oregon
United States	Skin Search of Rochester, Inc.	Rochester	New York
United States	Northwest Arkansas Clinical Trials Center, PLLC	Rogers	Arkansas
United States	University of Utah	Salt Lake City	Utah
United States	University Clinical Trials, Inc.	San Diego	California
United States	Derm Dox Center for Dermatology	Sugarloaf	Pennsylvania
United States	Children's National Hospital	Washington	District of Columbia
United States	Wake Forest School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
NFlection Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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 reduction	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.	182 days
Primary	Safety of once daily NFX-179 gel treatment for 182 days by adverse events and serious adverse events assessments	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).	182 days
Secondary	Percent of subjects with at least 50% Target cNF volume reduction after 182 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.	182 days
Secondary	Percent change in cNF volume over 182 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.	182 days
Secondary	Physician's Tumor Assessment of Target cNF severity over 182 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.	182 days
Secondary	Subject's Self-Assessment of Target cNF severity over 182 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.	182 days