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

Primary Purpose

Neurofibromatosis 1, Cutaneous Neurofibroma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
NFX-179 Gel
Vehicle Gel
Sponsored by
NFlection Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neurofibromatosis 1 focused on measuring NFX-179

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.
  5. Subject is willing to have the 5 Target cNF Tumors and the 1 Untreated cNF Tumor excised at the end of the treatment period
  6. Subject is willing to have hair in the area surrounding the Target cNF Tumors shaved, if necessary, to obtain photographs
  7. Subject is willing to minimize exposure of each Target cNF to natural and artificial ultraviolet radiation
  8. Subject is willing to forego treatment of the Target cNF Tumors, except protocol specified therapy, during the study
  9. 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
  10. Subject is willing and able to follow all study instructions and to attend all study visits.

Exclusion Criteria:

  1. 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
  2. Any Study cNF Tumor has ever been treated with an MEK inhibitor or a BRAF inhibitor
  3. 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
  4. Subject has a history of hypersensitivity to any of the ingredients in the study medications
  5. 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
  6. Subject has, in the investigator's opinion, clinically relevant history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis
  7. 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
  8. 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 Tumor or which exposes the subject to an unacceptable risk by study participation
  9. Subject has participated in an investigational drug trial in which administration of an investigational study medication occurred within the previous 30 days

Sites / Locations

  • Center for Dermatology Clinical Research, Inc.
  • Minnesota Clinical Study Center
  • Skin Search of Rochester, Inc.
  • DermResearch
  • University of Texas Southwestern Medical Center
  • The Education & Research Foundation, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

NFX-179 Gel Low

NFX-179 Gel Mid

NFX-179 Gel High

Vehicle Arm

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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
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).
Assessment of Adverse Events
Assessment of adverse events (AEs)

Secondary Outcome Measures

Percent Change in cNF Tumor Volume (Cubic Millimeters)
Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration
Systemic exposure of NFX-179 will be measured during the 28 days of QD applications at select investigative sites. Pharmacokinetic samples will be drawn at the baseline visit and week 4 visit. 5 time point samples will be collected at the week 4 visit.
Change in Physician Assessment of Tumor Severity Score
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). The assessment is performed at the Baseline visit and week 4 visit.
Change in Subject Self-Assessment of Tumor Severity Score
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). The assessment is performed at the Baseline visit and week 4 visit.

Full Information

First Posted
June 8, 2020
Last Updated
July 13, 2022
Sponsor
NFlection Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04435665
Brief Title
NFX-179 Topical Gel Treatment in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF)
Official Title
A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2a Study to Determine Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of NFX-179 Gel in Subjects With Cutaneous Neurofibromas
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
August 21, 2020 (Actual)
Primary Completion Date
April 8, 2021 (Actual)
Study Completion Date
April 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NFlection Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurofibromatosis 1, Cutaneous Neurofibroma
Keywords
NFX-179

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NFX-179 Gel Low
Arm Type
Experimental
Arm Description
NFX-179 Gel for topical administration, once daily for 28 days
Arm Title
NFX-179 Gel Mid
Arm Type
Experimental
Arm Description
NFX-179 Gel for topical administration, once daily for 28 days
Arm Title
NFX-179 Gel High
Arm Type
Experimental
Arm Description
NFX-179 Gel for topical administration, once daily for 28 days
Arm Title
Vehicle Arm
Arm Type
Placebo Comparator
Arm Description
Vehicle Gel, for topical administration, once daily for 28 days
Intervention Type
Drug
Intervention Name(s)
NFX-179 Gel
Intervention Description
gel for topical administration
Intervention Type
Drug
Intervention Name(s)
Vehicle Gel
Intervention Description
vehicle gel for topical administration
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
Baseline through Week 4
Title
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment
Description
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).
Time Frame
Baseline through Week 4
Title
Assessment of Adverse Events
Description
Assessment of adverse events (AEs)
Time Frame
Baseline through Week 8
Secondary Outcome Measure Information:
Title
Percent Change in cNF Tumor Volume (Cubic Millimeters)
Description
Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.
Time Frame
Baseline through Week 4
Title
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration
Description
Systemic exposure of NFX-179 will be measured during the 28 days of QD applications at select investigative sites. Pharmacokinetic samples will be drawn at the baseline visit and week 4 visit. 5 time point samples will be collected at the week 4 visit.
Time Frame
Baseline through Week 4
Title
Change in Physician Assessment of Tumor Severity Score
Description
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). The assessment is performed at the Baseline visit and week 4 visit.
Time Frame
Baseline through Week 4
Title
Change in Subject Self-Assessment of Tumor Severity Score
Description
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). The assessment is performed at the Baseline visit and week 4 visit.
Time Frame
Baseline through Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Subject is willing to have the 5 Target cNF Tumors and the 1 Untreated cNF Tumor excised at the end of the treatment period Subject is willing to have hair in the area surrounding the Target cNF Tumors shaved, if necessary, to obtain photographs Subject is willing to minimize exposure of each Target cNF to natural and artificial ultraviolet radiation Subject is willing to forego treatment of the Target cNF Tumors, except protocol specified therapy, during the study 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 Subject is willing and able to follow all study instructions and to attend all study visits. Exclusion Criteria: 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 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 Tumor or which exposes the subject to an unacceptable risk by study participation Subject has participated in an investigational drug trial in which administration of an investigational study medication occurred within the previous 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guy Webster, MD, PhD
Organizational Affiliation
NFlection Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Center for Dermatology Clinical Research, Inc.
City
Fremont
State/Province
California
ZIP/Postal Code
94538
Country
United States
Facility Name
Minnesota Clinical Study Center
City
New Brighton
State/Province
Minnesota
ZIP/Postal Code
55112
Country
United States
Facility Name
Skin Search of Rochester, Inc.
City
Rochester
State/Province
New York
ZIP/Postal Code
14623
Country
United States
Facility Name
DermResearch
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
The Education & Research Foundation, Inc.
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24501
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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