Clinical trial NCT05005845: NFX-179 Topical Gel Treatment for Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cutaneous Neurofibroma
Neurofibromatosis 1
Lead sponsor: NFlection Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 182 days
measure: Safety of once daily NFX-179 gel treatment for 182 days by adverse events and serious adverse events assessments
timeFrame: 182 days
Secondary outcomes:
measure: Percent of subjects with at least 50% Target cNF volume reduction after 182 days
timeFrame: 182 days
measure: Percent change in cNF volume over 182 days
timeFrame: 182 days
measure: Physician's Tumor Assessment of Target cNF severity over 182 days
timeFrame: 182 days
measure: Subject's Self-Assessment of Target cNF severity over 182 days
timeFrame: 182 days
Other outcomes:
measure: Patient Reported Outcome Measure to assess Target cNF symptoms over 182 days
timeFrame: 182 days
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Rogers
country: United States
facility: Northwest Arkansas Clinical Trials Center, PLLC
state: Arkansas
city: Fremont
country: United States
facility: Center for Dermatology Clinical Research, Inc.
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Diego
country: United States
facility: University Clinical Trials, Inc.
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Evanston
country: United States
facility: Northshore University HealthSystem
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Clinical Research Group
state: Indiana
city: Baltimore
country: United States
facility: The Johns Hopkins School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New Brighton
country: United States
facility: Minnesota Clinical Study Center
state: Minnesota
city: Omaha
country: United States
facility: Skin Specialists, P.C.
state: Nebraska
city: New York
country: United States
facility: Sadick Research Group, LLC
state: New York
city: Rochester
country: United States
facility: Skin Search of Rochester, Inc.
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
city: Mayfield Heights
country: United States
facility: Apex Clinical Research Center, LLC
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Sugarloaf
country: United States
facility: Derm Dox Center for Dermatology
state: Pennsylvania
city: Dallas
country: United States
facility: Dermatology Treatment and Research Center
state: Texas
city: Houston
country: United States
facility: UTHealth McGovern Medical School
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Lynchburg
country: United States
facility: The Education & Research Foundation, Inc.
state: Virginia
Study officials:
References: