Neurofibromatosis 1Phase 2NCT04435665

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

A Phase 2 study testing NFX-179 Gel in people with Neurofibromatosis 1 and Cutaneous Neurofibroma, run by NFlection Therapeutics, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Neurofibromatosis 1, Cutaneous Neurofibroma
What is being tested?: NFX-179 Gel
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 48 participants
Where: 6 sitesUnited States
Study dates: 21 Aug 2020to 14 Apr 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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

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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

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

DermResearch
Austin, Texas, 78758
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Center for Dermatology Clinical Research, Inc.
Fremont, California, 94538
The Education & Research Foundation, Inc.
Lynchburg, Virginia, 24501
Minnesota Clinical Study Center
New Brighton, Minnesota, 55112
Skin Search of Rochester, Inc.
Rochester, New York, 14623

Other trials in United States

About this study

Official title: 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

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.

Conditions: Neurofibromatosis 1, Cutaneous Neurofibroma
Being tested: NFX-179 Gel, Vehicle Gel
Keywords: NFX-179
Medical subject headings: Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NFX-179 GelDrug
gel for topical administration
Vehicle GelDrug
vehicle gel for topical administration

Study groups in NCT04435665
Study group	Role	What they receive
NFX-179 Gel Low	Experimental	NFX-179 Gel for topical administration, once daily for 28 days Receives: Drug: NFX-179 Gel
NFX-179 Gel Mid	Experimental	NFX-179 Gel for topical administration, once daily for 28 days Receives: Drug: NFX-179 Gel
NFX-179 Gel High	Experimental	NFX-179 Gel for topical administration, once daily for 28 days Receives: Drug: NFX-179 Gel
Vehicle Arm	Placebo comparator	Vehicle Gel, for topical administration, once daily for 28 days Receives: Drug: Vehicle Gel

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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).
Measured: Baseline through Week 4
Assessment of Adverse Events
Assessment of adverse events (AEs)
Measured: Baseline through Week 8

Secondary outcomes (4)

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.
Measured: Baseline through Week 4
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.
Measured: 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.
Measured: 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.
Measured: Baseline through Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Aug 202014 Apr 2021

First posted17 Jun 2020
Study start21 Aug 2020
Primary completion8 Apr 2021
Study completion14 Apr 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Neurofibromatosis 1Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04435665
Sponsor's protocol ID: NFX-179-NF1-201
Status last verified: Jul 2022
First submitted: 8 Jun 2020
Last updated: 9 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04435665
Acronym / sponsor ID: NFX-179-NF1-201
Conditions: Neurofibromatosis 1, Cutaneous Neurofibroma
Keywords: NFX-179
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: NFlection Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 21 Aug 2020 (actual)
Primary completion: 8 Apr 2021 (actual)
Study completion: 14 Apr 2021 (actual)
First posted: 17 Jun 2020 (actual)
Results: Posted 9 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
NFX-179 Gel Low	Experimental	Drug: NFX-179 GelNFX-179 Gel for topical administration, once daily for 28 days
NFX-179 Gel Mid	Experimental	Drug: NFX-179 GelNFX-179 Gel for topical administration, once daily for 28 days
NFX-179 Gel High	Experimental	Drug: NFX-179 GelNFX-179 Gel for topical administration, once daily for 28 days
Vehicle Arm	Placebo comparator	Drug: Vehicle GelVehicle Gel, for topical administration, once daily for 28 days

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NFX-179 Gelgel for topical administration	Drug	NFX-179 Gel High, NFX-179 Gel Low, NFX-179 Gel Mid
Vehicle Gelvehicle gel for topical administration	Drug	Vehicle Arm

Primary outcome

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
Time frame: 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
Time frame: 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
Time frame: Baseline through Week 8
Assessment of adverse events (AEs)

4 secondary outcomes

Percent Change in cNF Tumor Volume (Cubic Millimeters)
Time frame: Baseline through Week 4
Systemic Exposure of NFX-179 Gel Measured by Plasma Concentration
Time frame: Baseline through Week 4
Change in Physician Assessment of Tumor Severity Score
Time frame: Baseline through Week 4
Change in Subject Self-Assessment of Tumor Severity Score
Time frame: Baseline through Week 4

Results and safety

Results posted to the registry on 9 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NFX-179 Gel Low (0.05%)	12	12
NFX-179 Gel Mid (0.15%)	11	11
NFX-179 Gel High (0.50%)	12	12
Vehicle Arm (Placebo)	13	12

Primary outcome: 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

Time frame: Baseline through Week 4. Mean (Standard Deviation). Unit: % reduction in pERK to total ERK

Measure	Vehicle Arm (Placebo) n = 12	NFX-179 Gel Low (0.05%) n = 11	NFX-179 Gel Mid (0.15%) n = 10	NFX-179 Gel High (0.50%) n = 11
Value	0.3054 (0.1369)	0.2734 (0.1257)	0.2267 (0.1272)	0.1627 (0.0686)

Population analysed: 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.

Primary outcome: Safety and Tolerability of NFX-179 Gel Measured by Local Tolerability Assessment

Time frame: Baseline through Week 4. Number. Unit: events

Measure	Vehicle Arm (Placebo) n = 13	NFX-179 Gel Low (0.05%) n = 12	NFX-179 Gel Mid (0.15%) n = 11	NFX-179 Gel High (0.50%) n = 12
subject reported instances of mild pruritus	2	5	7	4
subject reported instances of moderate pruritus	0	1	2	0
subject reported instances of mild burning	6	0	0	0
subject reported instances of mild stinging	0	0	0	4
investigator reported instances of mild erythema	0	2	1	1
investigator reported instances of moderate erythema	0	0	0	1
investigator reported instances of mild edema	0	0	1	0
investigator reported instances of scabbing/crusting	0	0	0	1

Primary outcome: Assessment of Adverse Events

Time frame: Baseline through Week 8. Number. Unit: Subjects

Measure	Vehicle Arm (Placebo) n = 13	NFX-179 Gel Low (0.05%) n = 12	NFX-179 Gel Mid (0.15%) n = 11	NFX-179 Gel High (0.50%) n = 12
Number of subjects with treatment-emergent AEs	2	2	1	3
Number of subects with related treatment-emergent AEs	0	0	0	1
Number of subjects withdrawn due to AEs	0	0	0	0
Subjects with mild treatment-emergent AEs	1	0	0	3
Subjects with moderate treatment-emergent AEs	1	2	1	0
Subjects with severe treatment-emergent AEs	0	0	0	0

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 56 Days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vehicle Arm (Placebo)	0 of 13 (0%)	2 of 13 (15.4%)	0 of 13
NFX-179 Gel Low (0.05%)	0 of 12 (0%)	2 of 12 (16.7%)	0 of 12
NFX-179 Gel Mid (0.15%)	0 of 11 (0%)	2 of 11 (18.2%)	0 of 11
NFX-179 Gel High (0.50%)	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Guy Webster, MD, PhD study director

NFlection Therapeutics

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NFX-179 Gel in people with Neurofibromatosis 1 and Cutaneous Neurofibroma, run by NFlection Therapeutics, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Baseline through Week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04435665.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2022.