A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Phase 2 Dose-Response Study to Determine Safety and Effectiveness of Two Concentrations 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
- 199
- 试验地点
- 23
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a randomized, double-blind, vehicle-controlled, parallel group dose response study evaluating the safety and effectiveness of 2 concentrations of NFX-179 gel in participants with cNF. At Visit 1 (Screening visit), the investigator will identify 10 Target cNFs that fulfil the enrollment criteria. The Target cNFs must be located on the participant's face, anterior trunk, or upper extremities. Two Target cNFs must be on the face and 8 must be on the anterior trunk or upper extremities. The study medication will be applied topically once daily to the Target cNFs for 182 days (26 weeks). During the duration of the study participants will be evaluated for safety and efficacy.
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
- •Participant is at least 18 years of age
- •Participant must provide written informed consent prior to any study procedures
- •Participant must have a clinical diagnosis of NF1
- •Participant has 10 clinically diagnosed Target cNFs with preferably 2 Target cNFs located on the face and 8 Target cNFs located on the anterior trunk or upper extremities. Alternatively, at least 1 Target cNF is located on the face, in which case 9 Target cNFs must be located on the anterior trunk or upper extremities. Each Target cNF must meet the following criteria:
- •Has, in the investigator's opinion, a clinically typical appearance
- •Is not within 1 centimeter (cm) of the orbital rim
- •Is not covered with hair that might, in the investigator's opinion, interfere with obtaining photographs or impair evaluation of the cNF
- •Has a Physician's Tumor Assessment grade ≥2
- •Is dome shaped
- •Is not pedunculated
- •Is a discrete cNF surrounded by sufficient non-affected skin that, in the investigator's opinion:
- •The dimensions can be measured
- •The perimeter can be outlined in the study photographs
- •Is not irritated (or example, bleeding, inflamed)
- •Is not in an area participant to repeated trauma (or example, area that is shaved, on the beltline, under a bra strap, etc.)
- •Does not have an active cutaneous infection
- •Target cNFs on the face must have the following tumor dimensions:
- •Has a length that is ≥5 millimeters (mm) and ≤14 mm
- •Has a width that is ≥5 mm and ≤14 mm
- •Has a height that is ≥2 mm.
- •Target cNFs on the anterior trunk or upper extremities must have the following tumor dimensions:
- •Has a length that is ≥ 7mm and ≤14 mm
- •Has a width that is ≥5 mm and ≤14 mm
- •Has a height that is ≥2 mm.
- •Participant agrees to avoid exposure of Target cNFs to excessive sunlight and to use her/his routine sunscreen if excessive exposure cannot be avoided
- •Participant agrees not to use tanning beds
- •Participant is willing to forego treatment of each Target cNF, except protocol specified therapy, during the study
- •Female participants 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
- •Participant is willing and able to follow all study instructions and to attend all study visits.
排除标准
- •Participant has used any of the following topical therapies within the specified period prior to Visit 1 (screening visit) on or in proximity to any Target cNF that, in the investigator's opinion, impairs evaluation of any the cNFs or which exposes the participant to an unacceptable risk by study participation:
- •Corticosteroids; 30 days
- •Prescription retinoids (for example, tazarotene, tretinoin, adapalene); 30 days
- •> 5% of an alpha-hydroxy acid (for example, glycolic acid, lactic acid); 30 days
- •Fluorouracil; 30 days
- •Imiquimod; 30 days
- •LASER, light (for example, intense pulsed light [IPL], photo-dynamic therapy [PDT]) or other energy-based therapy; 180 days
- •Mitogen-activated protein kinase (MEK) inhibitor or V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) inhibitor; ever.
- •The participant has used any of the following systemic medications therapies within the specified period prior to Visit 1 (screening visit):
- •Retinoids (for example, etretinate, isotretinoin); 90 days
- •MEK inhibitors; 180 days
- •BRAF inhibitors; 180 days
- •Participant has a history of hypersensitivity to any of the ingredients in the study medications
- •Participant has any known intercurrent illness or physical condition that would, in the investigator's opinion, impair evaluation of a Target cNF or which exposes the participant to an unacceptable risk by study participation
- •Participant has, in the investigator's opinion, clinically relevant history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis
- •Participant 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
- •Participant has any condition (for example, other skin conditions or diseases, metabolic dysfunction, physical examination findings, clinical laboratory findings) or situation (for example, vacation, scheduled surgery) that would, in the investigator's opinion, impair evaluation of a Target cNF or which exposes the participant to an unacceptable risk by study participation
- •Participant 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 Topical Gel 0.5%
NFX-179 topical gel 0.5% will be applied once daily to the target cutaneous neurofibromas (cNFs) for 182 days.
干预措施: NFX-179 gel (Drug)
NFX-179 Topical Gel 1.5%
NFX-179 topical gel 1.5% will be applied once daily to the target cNFs for 182 days.
干预措施: NFX-179 gel (Drug)
NFX-179 Topical Gel Vehicle
NFX-179 topical gel vehicle will be applied once daily to the target cNFs for 182 days.
干预措施: Vehicle gel (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline (Day 1) up to Day 211
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an event that occurred or worsened on or after the first dose of study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Percentage of Participants With At Least 50% of Target Lesions With 50% Reduction in cNF Volume Above the Surrounding Non-tumor Skin
时间窗: Day 182
Treatment effectiveness was measured by the percentage of treated participants with at least 50% of target lesions with 50% reduction in cNF volume after 6 months of treatment. Tumor dimensions were measured using a standardized ruler.
次要结局
- Percentage of Participants With At Least 50% of Target Lesions With 50% Reduction in cNF Height Above the Surrounding Non-tumor Skin(Day 182)
- Mean Percent Change From Baseline in cNF Volume at Day 182 Based on cNF Volume Derived From Ruler Measurements(Baseline, Day 182)
- Change From Baseline in Tumor Severity Score Per Physician's Tumor Assessment (PTA) at Day 182(Baseline, Day 182)
- Change From Baseline in Tumor Severity Score Per Subject's Self-Assessment (SSA) at Day 182(Baseline, Day 182)