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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NFX-179 Gel Low | Experimental | NFX-179 Gel for topical administration, once daily for 28 days |
|
| NFX-179 Gel Mid | Experimental | NFX-179 Gel for topical administration, once daily for 28 days |
|
| NFX-179 Gel High | Experimental | NFX-179 Gel for topical administration, once daily for 28 days |
|
| Vehicle Arm | Placebo Comparator | Vehicle Gel, for topical administration, once daily for 28 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NFX-179 Gel | Drug | gel for topical administration |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline through Week 4 |
| Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration |
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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:
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:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Guy Webster, MD, PhD | NFlection Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Dermatology Clinical Research, Inc. | Fremont | California | 94538 | United States | ||
| Minnesota Clinical Study Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | NFX-179 Gel Low (0.05%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration |
| FG001 | NFX-179 Gel Mid (0.15%) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Full Protocol | Jul 24, 2020 |
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| Vehicle Gel | Drug | vehicle gel for topical administration |
|
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. |
| Baseline through Week 4 |
| 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. | Baseline through Week 4 |
| 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. | Baseline through Week 4 |
| New Brighton |
| Minnesota |
| 55112 |
| United States |
| Skin Search of Rochester, Inc. | Rochester | New York | 14623 | United States |
| DermResearch | Austin | Texas | 78758 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| The Education & Research Foundation, Inc. | Lynchburg | Virginia | 24501 | United States |
NFX-179 Gel for topical administration, once daily for 28 days
NFX-179 Gel 0.15%
NFX-179 Gel: gel for topical administration
| FG002 | NFX-179 Gel High (0.50%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration |
| FG003 | Vehicle Arm (Placebo) | Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration |
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NFX-179 Gel Low (0.05%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration |
| BG001 | NFX-179 Gel Mid (0.15%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration |
| BG002 | NFX-179 Gel High (0.50%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration |
| BG003 | Vehicle Arm (Placebo) | Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | The p-ERK analysis included all available p-ERK data from tumors determined by histology to be cNF tumors. Missing data were due to missing or non-analyzable tumor samples or tumor samples shown to come from non-cNF tumors upon histologic review. Therefore the number of participants is not the same as those in the participant flow. | Posted | Mean | Standard Deviation | % reduction in pERK to total ERK | Baseline through Week 4 | Tumors | Tumors |
|
|
| ||||||||||||||||||||||||||||||||
| Primary | 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). | Posted | Number | events | Baseline through Week 4 |
| ||||||||||||||||||||||||||||||||||||||
| Primary | Assessment of Adverse Events | Assessment of adverse events (AEs) | Posted | Number | Subjects | Baseline through Week 8 |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | Standard Deviation | percentage change | Baseline through Week 4 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Pharmacokinetic data from subjects treated with active NFX-179 gel was performed, which does not include samples from subjects treated with Vehicle gel (placebo). As such, no analysis pharmacokinetic analysis was performed in the Vehicle Arm. | Posted | Number | ng/mL | Baseline through Week 4 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | Standard Deviation | Change in Investigator Assessment score | Baseline through Week 4 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | Standard Deviation | change in subject assessment score | Baseline through Week 4 |
|
Up to 56 Days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vehicle Arm (Placebo) | Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration | 0 | 13 | 0 | 13 | 2 | 13 |
| EG001 | NFX-179 Gel Low (0.05%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration | 0 | 12 | 0 | 12 | 2 | 12 |
| EG002 | NFX-179 Gel Mid (0.15%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration | 0 | 11 | 0 | 11 | 2 | 11 |
| EG003 | NFX-179 Gel High (0.50%) | NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration | 0 | 12 | 0 | 12 | 4 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Oedema peripheral | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Multiple allergies | Immune system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Postoperative wound infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Corona test positive | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Sleep apnea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Menopause | Social circumstances | MedDRA 21.0 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Operations | NFlection | 7078532199 | comara@nflectionrx.com |
| Aug 25, 2021 |
| Prot_SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 1 | Jul 20, 2020 | Aug 25, 2021 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 2 | Mar 25, 2021 | Aug 25, 2021 | Prot_002.pdf |
| Prot | Yes | No | No | Study Protocol: Amendment 3 | Apr 1, 2021 | Aug 25, 2021 | Prot_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 3, 2020 | Aug 25, 2021 | ICF_004.pdf |
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| ID | Term |
|---|---|
| D009456 | Neurofibromatosis 1 |
| ID | Term |
|---|---|
| D017253 | Neurofibromatoses |
| D009455 | Neurofibroma |
| D018317 | Nerve Sheath Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009386 | Neoplastic Syndromes, Hereditary |
| D020752 | Neurocutaneous Syndromes |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| Male |
|
| White |
|
| Asian |
|
| Black/African American |
|
| Hispanic or Latino |
|
| Not Hispanic or Latino |
|
| Not reported |
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| Tumors |
|
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| Units |
|---|
| Counts |
|---|
| Participants |
|
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| OG003 |
| NFX-179 Gel High (0.50%) |
NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration |
|
|
NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration |
|
|
NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration |
|
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