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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 6
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
NFX-179 Gel Low
NFX-179 Gel for topical administration, once daily for 28 days
干预措施: NFX-179 Gel (Drug)
NFX-179 Gel Mid
NFX-179 Gel for topical administration, once daily for 28 days
干预措施: NFX-179 Gel (Drug)
NFX-179 Gel High
NFX-179 Gel for topical administration, once daily for 28 days
干预措施: NFX-179 Gel (Drug)
Vehicle Arm
Vehicle Gel, for topical administration, once daily for 28 days
干预措施: Vehicle Gel (Drug)
结局指标
主要结局
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
时间窗: Baseline through Week 4
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
时间窗: Baseline through Week 4
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
时间窗: Baseline through Week 8
Assessment of adverse events (AEs)
次要结局
- 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)