Cutaneous Neurofibroma, Neurofibromatosis 1
Conditions
Brief summary
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.
Interventions
DRUGNFX-179 gel
NFX-179 topical gel is the active investigational product being studied
DRUGVehicle gel
NFX-179 vehicle gel is the placebo comparator for this study
Sponsors
NFlection Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participant is at least 18 years of age 2. Participant must provide written informed consent prior to any study procedures 3. Participant must have a clinical diagnosis of NF1 4. 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. 5. Participant agrees to avoid exposure of Target cNFs to excessive sunlight and to use her/his routine sunscreen if excessive exposure cannot be avoided 6. Participant agrees not to use tanning beds 7. Participant is willing to forego treatment of each Target cNF, except protocol specified therapy, during the study 8. 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 9. Participant is willing and able to follow all study instructions and to attend all study visits.
Exclusion criteria
1. 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. 2. 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 3. Participant has a history of hypersensitivity to any of the ingredients in the study medications 4. 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 5. Participant has, in the investigator's opinion, clinically relevant history of liver disease, including viral hepatitis, current alcohol abuse, or cirrhosis 6. 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 7. 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 8. Participant has participated in an investigational drug trial in which administration of an investigational study medication occurred within the previous 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least 50% of Target Lesions With 50% Reduction in cNF Height Above the Surrounding Non-tumor Skin | Day 182 | Treatment effectiveness was measured by the percentage of treated participants with at least 50% of target lesions with 50% reduction in cNF height after 6 months of treatment. Tumor dimensions were measured using a standardized ruler. |
| Mean Percent Change From Baseline in cNF Volume at Day 182 Based on cNF Volume Derived From Ruler Measurements | Baseline, Day 182 | Mean percent change of tumor volume was calculated from ruler measurements throughout the course of treatment. Presented here are data analyzed at the participant level. |
| Change From Baseline in Tumor Severity Score Per Physician's Tumor Assessment (PTA) at Day 182 | Baseline, Day 182 | Effect of treatment with the PTA was the investigator's assessment of the average overall severity of each Target cNF tumor at a particular time point. The PTA is a 5-point measuring tumor severity (0 = clear/none, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe). Presented here are data analyzed at the participant level. |
| Change From Baseline in Tumor Severity Score Per Subject's Self-Assessment (SSA) at Day 182 | Baseline, Day 182 | The SSA was the participant's assessment of the average overall severity of each Target cNF at a particular time point. The SSA is a 5-point measuring tumor severity (0 = clear/none, 1 = almost clear, 2 = mild, 3 = moderate, and 4 = severe). |
Countries
United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 50.77 years STANDARD_DEVIATION 12.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 35 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 164 Participants |
| Sex: Female, Male Female | 134 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 1 / 66 | 1 / 66 |
| other Total, other adverse events | 35 / 67 | 36 / 66 | 49 / 66 |
| serious Total, serious adverse events | 3 / 67 | 4 / 66 | 3 / 66 |
Outcome results
None listed