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

NCT04435665 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NFX-179-NF1-201
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 6

Brief Summary

This study will enroll and treat subjects with cutaneous neurofibromas with NFX-179, a topical study drug. Eligible subjects will receive treatment for 28 days and be observed by a study doctor for approximately 56 days. Subjects will be randomly assigned to 1 of 4 treatment groups. 3 of the treatment groups will receive a specific dose NFX-179, and 1 group will receive placebo. The subject, study doctor, and NFlection Therapeutics will not know what treatment group each subject is assigned. Study participation requires at least 7 clinic visits, blood, urine, and tissue collection, images of the treated cutaneous neurofibromas, electrocardiograms, and information regarding the subject's medical and disease history.

Conditions

Neurofibromatosis 1; Cutaneous Neurofibroma

Keywords

NFX-179

Outcome Measures

Primary Outcomes (3)

• Phospho-erk (p-ERK) Levels of Target cNF Tumors in NFX-179 Gel Group and Vehicle Gel Group After 28 Days of Once-daily (QD) Application

  Pharmacodynamic activity (biochemical and physiologic effects of drugs) of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target cNF Tumors in each NFX-179 Gel group compared with the Vehicle Gel group after 28 days of once-daily (QD) application will be measured at Week 4

  Baseline through Week 4

• Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment

  Safety and tolerability will be measured via a local tolerability assessment. 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).

  Baseline through Week 4

• Assessment of Adverse Events

  Assessment of adverse events (AEs)

  Baseline through Week 8

Secondary Outcomes (4)

• Percent Change in cNF Tumor Volume (Cubic Millimeters)

  Baseline through Week 4

• Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration

  Baseline through Week 4

• Change in Physician Assessment of Tumor Severity Score

  Baseline through Week 4

• Change in Subject Self-Assessment of Tumor Severity Score

  Baseline through Week 4

Study Arms (4)

NFX-179 Gel Low

EXPERIMENTAL

NFX-179 Gel for topical administration, once daily for 28 days

Drug: NFX-179 Gel

NFX-179 Gel Mid

EXPERIMENTAL

NFX-179 Gel for topical administration, once daily for 28 days

Drug: NFX-179 Gel

NFX-179 Gel High

EXPERIMENTAL

NFX-179 Gel for topical administration, once daily for 28 days

Drug: NFX-179 Gel

Vehicle Arm

PLACEBO COMPARATOR

Vehicle Gel, for topical administration, once daily for 28 days

Drug: Vehicle Gel

Interventions

NFX-179 Gel DRUG

gel for topical administration

NFX-179 Gel High; NFX-179 Gel Low; NFX-179 Gel Mid

Vehicle Gel DRUG

vehicle gel for topical administration

Vehicle Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is at least 18 years of age
• Subject must provide written informed consent prior to any study procedures
• Subject must have a clinical diagnosis of NF1
• Subject has 6 Study cNF Tumors (5 Target cNF Tumors \[1 on the face; 4 on the anterior trunk or upper extremities\] that will be treated with the assigned study medication;1 Untreated cNF Tumor on the anterior trunk or upper extremities) that each meet the following criteria:
• Has, in the investigator's opinion, a clinically typical appearance
• Is dome shaped
• Is not pedunculated
• Is a discrete tumor
• Is not irritated
• 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
• Has a diameter that is ≥5mm and ≤10mm
• Has a height of ≥2mm
• Is, when centered in the center of the provided template, the only cNF tumor visible
• Is not within 5mm of the orbital rim.

You may not qualify if:

• Subject has applied any of the following topical products in the previous 30 days on or in proximity to any Study cNF Tumor that, in the investigator's opinion, impairs evaluation of any the tumor or which exposes the subject to an unacceptable risk by study participation:
• Corticosteroids
• Retinoids (e.g., tazarotene, tretinoin, adapalene)
• \> 5% of an alpha-hydroxy acid (e.g., glycolic acid, lactic acid)
• Fluorouracil
• Imiquimod
• Any Study cNF Tumor has ever been treated with an MEK inhibitor or a BRAF inhibitor
• The subject has used any of the following systemic medications in the noted time period:
• Retinoids (e.g., etretinate, isotretinoin) within the previous 90 days
• MEK inhibitors within the previous 180 days
• BRAF inhibitors within the previous 180 days
• Subject has a history of hypersensitivity to any of the ingredients in the study medications
• Subject has any known intercurrent illness or physical condition that would, in the investigator's opinion, impair evaluation of a Target cNF Tumor or which exposes the subject to an unacceptable risk by study participation
• Subject has, in the investigator's opinion, clinically relevant history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis
• 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

Sponsors & Collaborators

• NFlection Therapeutics, Inc.: lead

Study Sites (6)

Center for Dermatology Clinical Research, Inc.

Fremont, California, 94538, United States

Location

Minnesota Clinical Study Center

New Brighton, Minnesota, 55112, United States

Location

Skin Search of Rochester, Inc.

Rochester, New York, 14623, United States

Location

DermResearch

Austin, Texas, 78758, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The Education & Research Foundation, Inc.

Lynchburg, Virginia, 24501, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 1

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Director of Clinical Operations
• Organization: NFlection

comara@nflectionrx.com

7078532199

Study Officials

• Guy Webster, MD, PhD

  NFlection Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 17, 2020
• Study Start: August 21, 2020
• Primary Completion: April 8, 2021
• Study Completion: April 14, 2021
• Last Updated: August 9, 2022
• Results First Posted: August 9, 2022

Record last verified: 2022-07

Locations

US (6)