Trial Outcomes & Findings for NFX-179 Topical Gel Treatment in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF) (NCT NCT04435665)

NCT ID: NCT04435665

Last Updated: 2022-08-09

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 48 participants
• Primary outcome timeframe: Baseline through Week 4
• Results posted on: 2022-08-09

Participant Flow

Participant milestones

Measure	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	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	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	Vehicle Arm (Placebo) Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration
Overall Study STARTED	12	11	12	13
Overall Study COMPLETED	12	11	12	12
Overall Study NOT COMPLETED	0	0	0	1

Reasons for withdrawal

Measure	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	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	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	Vehicle Arm (Placebo) Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration
Overall Study Lost to Follow-up	0	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	NFX-179 Gel Low (0.05%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration	Vehicle Arm (Placebo) n=13 Participants Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	Total n=48 Participants Total of all reporting groups
Age, Continuous	51.1 years n=5 Participants	49.5 years n=7 Participants	43.5 years n=5 Participants	45.2 years n=4 Participants	47.8 years n=21 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	7 Participants n=4 Participants	32 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	16 Participants n=21 Participants
Race/Ethnicity, Customized Non-white	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	11 Participants n=4 Participants	39 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Black/African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	9 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	11 Participants n=4 Participants	36 Participants n=21 Participants
Race/Ethnicity, Customized Not reported	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline through Week 4

Population: 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.

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

Outcome measures

Measure	Vehicle Arm (Placebo) n=53 Tumors Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=53 Tumors NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=47 Tumors NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=53 Tumors NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
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	0.3054 % reduction in pERK to total ERK Standard Deviation 0.1369	0.2734 % reduction in pERK to total ERK Standard Deviation 0.1257	0.2267 % reduction in pERK to total ERK Standard Deviation 0.1272	0.1627 % reduction in pERK to total ERK Standard Deviation 0.0686

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Vehicle Arm (Placebo) n=13 Participants Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment subject reported instances of mild pruritus	2 events	5 events	7 events	4 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment subject reported instances of moderate pruritus	0 events	1 events	2 events	0 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment subject reported instances of mild burning	6 events	0 events	0 events	0 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment subject reported instances of mild stinging	0 events	0 events	0 events	4 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment investigator reported instances of mild erythema	0 events	2 events	1 events	1 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment investigator reported instances of moderate erythema	0 events	0 events	0 events	1 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment investigator reported instances of mild edema	0 events	0 events	1 events	0 events
Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment investigator reported instances of scabbing/crusting	0 events	0 events	0 events	1 events

PRIMARY outcome

Timeframe: Baseline through Week 8

Assessment of adverse events (AEs)

Outcome measures

Measure	Vehicle Arm (Placebo) n=13 Participants Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
Assessment of Adverse Events Number of subjects with treatment-emergent AEs	2 Subjects	2 Subjects	1 Subjects	3 Subjects
Assessment of Adverse Events Number of subects with related treatment-emergent AEs	0 Subjects	0 Subjects	0 Subjects	1 Subjects
Assessment of Adverse Events Number of subjects withdrawn due to AEs	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Assessment of Adverse Events Subjects with mild treatment-emergent AEs	1 Subjects	0 Subjects	0 Subjects	3 Subjects
Assessment of Adverse Events Subjects with moderate treatment-emergent AEs	1 Subjects	2 Subjects	1 Subjects	0 Subjects
Assessment of Adverse Events Subjects with severe treatment-emergent AEs	0 Subjects	0 Subjects	0 Subjects	0 Subjects

SECONDARY outcome

Timeframe: Baseline through Week 4

Percent change in cNF tumor volume after 28 days of QD applications of NFX-179 gel based on tumor volume derived from ruler measurements.

Outcome measures

Measure	Vehicle Arm (Placebo) n=13 Participants Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
Percent Change in cNF Tumor Volume (Cubic Millimeters)	-8.0 percentage change Standard Deviation 18.2	-1.6 percentage change Standard Deviation 22.1	-11.9 percentage change Standard Deviation 29.4	-16.7 percentage change Standard Deviation 30.3

SECONDARY outcome

Timeframe: Baseline through Week 4

Population: 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.

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.

Outcome measures

Measure	Vehicle Arm (Placebo) Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=1 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=2 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=1 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration Baseline, pre dose (0 hour)	—	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration Week 4, pre dose (0 hour)	—	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification	0.439 ng/mL
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration Week 4, post dose 30 min	—	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification	0.887 ng/mL
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration Week 4, post dose 1 hour	—	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification	0.573 ng/mL
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration Week 4, post dose 2 hours	—	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification	0.718 ng/mL
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration Week 4, post dose 4 hours	—	NA ng/mL below the lower limit of quantification	NA ng/mL below the lower limit of quantification	0.528 ng/mL

SECONDARY outcome

Timeframe: Baseline through Week 4

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.

Outcome measures

Measure	Vehicle Arm (Placebo) n=12 Participants Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
Change in Physician Assessment of Tumor Severity Score Visit 2	2.74 Change in Investigator Assessment score Standard Deviation 0.53	2.46 Change in Investigator Assessment score Standard Deviation 0.62	2.60 Change in Investigator Assessment score Standard Deviation 0.57	2.65 Change in Investigator Assessment score Standard Deviation 0.70
Change in Physician Assessment of Tumor Severity Score Visit 5	2.51 Change in Investigator Assessment score Standard Deviation 0.58	3.58 Change in Investigator Assessment score Standard Deviation 0.62	2.50 Change in Investigator Assessment score Standard Deviation 0.59	2.70 Change in Investigator Assessment score Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline through Week 4

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.

Outcome measures

Measure	Vehicle Arm (Placebo) n=12 Participants Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 Participants NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
Change in Subject Self-Assessment of Tumor Severity Score Visit 2	2.75 change in subject assessment score Standard Deviation 0.73	2.81 change in subject assessment score Standard Deviation 0.53	2.71 change in subject assessment score Standard Deviation 0.38	2.38 change in subject assessment score Standard Deviation 0.71
Change in Subject Self-Assessment of Tumor Severity Score Visit 5	2.50 change in subject assessment score Standard Deviation 0.60	2.76 change in subject assessment score Standard Deviation 0.55	2.50 change in subject assessment score Standard Deviation 0.56	2.39 change in subject assessment score Standard Deviation 0.61

Adverse Events

Vehicle Arm (Placebo)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

NFX-179 Gel Low (0.05%)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

NFX-179 Gel Mid (0.15%)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

NFX-179 Gel High (0.50%)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vehicle Arm (Placebo) n=13 participants at risk Vehicle Gel, for topical administration, once daily for 28 days Vehicle Gel placebo Vehicle Gel: vehicle gel for topical administration	NFX-179 Gel Low (0.05%) n=12 participants at risk NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.05% NFX-179 Gel: gel for topical administration	NFX-179 Gel Mid (0.15%) n=11 participants at risk NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.15% NFX-179 Gel: gel for topical administration	NFX-179 Gel High (0.50%) n=12 participants at risk NFX-179 Gel for topical administration, once daily for 28 days NFX-179 Gel 0.50% NFX-179 Gel: gel for topical administration
General disorders Oedema peripheral	0.00% 0/13 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	9.1% 1/11 • Number of events 1 • Up to 56 Days	0.00% 0/12 • Up to 56 Days
Immune system disorders Multiple allergies	0.00% 0/13 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	8.3% 1/12 • Number of events 1 • Up to 56 Days
Infections and infestations Postoperative wound infection	0.00% 0/13 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	8.3% 1/12 • Number of events 1 • Up to 56 Days
Investigations Corona test positive	15.4% 2/13 • Number of events 2 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	0.00% 0/12 • Up to 56 Days
Psychiatric disorders Anxiety	0.00% 0/13 • Up to 56 Days	8.3% 1/12 • Number of events 1 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	0.00% 0/12 • Up to 56 Days
Respiratory, thoracic and mediastinal disorders Sleep apnea syndrome	0.00% 0/13 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	9.1% 1/11 • Number of events 1 • Up to 56 Days	0.00% 0/12 • Up to 56 Days
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/13 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	8.3% 1/12 • Number of events 1 • Up to 56 Days
Skin and subcutaneous tissue disorders Basal cell carcinoma	0.00% 0/13 • Up to 56 Days	8.3% 1/12 • Number of events 1 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	0.00% 0/12 • Up to 56 Days
Social circumstances Menopause	0.00% 0/13 • Up to 56 Days	0.00% 0/12 • Up to 56 Days	0.00% 0/11 • Up to 56 Days	8.3% 1/12 • Number of events 1 • Up to 56 Days

Additional Information

Director of Clinical Operations

NFlection

Phone: 7078532199

Email: comara@nflectionrx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place