Clinical Trials /

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

NCT04435665

Description:

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.

Related Conditions:
  • Neurofibromatosis Type 1
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: NFX-179-NF1-201
  • NCT ID: NCT04435665

Conditions

  • Neurofibromatosis 1
  • Cutaneous Neurofibroma

Interventions

DrugSynonymsArms
NFX-179 GelNFX-179 Gel High
Vehicle GelVehicle Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
NFX-179 Gel LowExperimentalNFX-179 Gel for topical administration, once daily for 28 days
  • NFX-179 Gel
NFX-179 Gel MidExperimentalNFX-179 Gel for topical administration, once daily for 28 days
  • NFX-179 Gel
NFX-179 Gel HighExperimentalNFX-179 Gel for topical administration, once daily for 28 days
  • NFX-179 Gel
Vehicle ArmPlacebo ComparatorVehicle Gel, for topical administration, once daily for 28 days
  • Vehicle Gel

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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Time Frame:Baseline through Week 4
Safety Issue:
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

Secondary Outcome Measures

Measure:Percent change in cNF tumor volume (cubic millimeters)
Time Frame:Baseline through Week 4
Safety Issue:
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, ultrasound measurements and digital images. All modes of tumor volume measurement are reported in cubic millimeters.
Measure:Systemic exposure of NFX-179 Gel measured by plasma concentration
Time Frame:Baseline through Week 4
Safety Issue:
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.
Measure:Physician Tumor Assessment of the average overall severity of cNF tumor
Time Frame:Baseline through Week 4
Safety Issue:
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.
Measure:Subject Self-Assessment of the average overall severity of each Target cNF tumor
Time Frame:Baseline through Week 4
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NFlection Therapeutics, Inc.

Trial Keywords

  • NFX-179

Last Updated

June 16, 2020