Use of Topical Liquid Diclofenac Following Laser Microporation of Cutaneous Neurofibromas in Patients With NF1

NCT03090971 | Completed Phase 2 DMC

• 1 other identifier: NX101-02-2016
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open, controlled, prospective, proof-of-concept study, in 7 patients presenting NF1 and cutaneous neurofibromas. This study will include three treatment visits to the study center and three follow-up visits. Treatment will consist of two stages: neurofibroma microporation using the laser device, followed by topical application of one drop of diclofenac 25mg/ml on the surface of the neurofibroma; followed by re-application of one drop of diclofenac, twice daily, for three days. The applications subsequent to the first application will be performed by the patients. Subjects will return to the study center at three day intervals (Assessments 2 \& 3) for new microporation and topical diclofenac application, followed by at-home topical diclofenac application for three more days. Assessment 4 will take place 3 days after Assessment 3. Assessment 5 will take place 7 days after the end of the treatment period and Assessment 6 at 30 days after the last application of study drug. The primary efficacy variable in this study is the inflammatory process with the presence of tissue necrosis. The primary safety variable is the occurrence of adverse events considered to be associated with the study drug, occurring during the treatment period.

Conditions

Neurofibromatosis 1; Cutaneous Neurofibroma

Outcome Measures

Primary Outcomes (1)

• Efficacy - presence of inflammatory process in the treated neurofibromas

  Inflammatory process (redness, exculceration)

  Throughout the 7-day treatment period and subsequent 30-day follow-up period

Secondary Outcomes (4)

• Efficacy - presence of tissue necrosis in treated neurofibromas

  Throughout the 7-day treatment period and subsequent 30-day follow-up period

• Efficacy - neurofibroma size

  Throughout the 7-day treatment period and subsequent 30-day follow-up period

• Efficacy - neurofibroma detatchment

  Throughout the 7-day treatment period and subsequent 30-day follow-up period

• Safety - Adverse events

  Throughout the 7-day treatment period and subsequent 30-day follow-up period

Study Arms (1)

Cutaneous neurofibromas

EXPERIMENTAL

Each subject will have two treatment neurofibromas and two control neurofibromas. Following microporation, the two treatment neurofibromas will be treated with topical diclofenac while the two control neurofibromas will be treated with topical saline.

Drug: Diclofenac Sodium; Drug: Saline Solution

Interventions

Diclofenac Sodium DRUG

Following microporation, treatment neurofibromas will receive treatment with topical diclofenac

Cutaneous neurofibromas

Saline Solution DRUG

Following microporation, control neurofibromas will receive treatment with topical saline

Cutaneous neurofibromas

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults of both genders, between the ages of 18 and 65;
• NF1, diagnosed clinically by a neurologist, dermatologist, or other specialist knowledgeable about the disease, and defined as:
• A known mutation in the gene coding for neurofibromin
• or, the presence of 2 of the following 7 clinical manifestations of NF1:
• ≥ 6 café-au-lait macules on the body with diameters greater than 15mm in the greatest diameter;
• two or more neurofibromas of any type or one plexiform neurofibroma
• inguinal or axillary freckling
• two or more Lisch nodules (iris hamartomas)
• optic glioma
• a distinct osseous lesion, such as sphenoid wing dysplasia, pseudoarthrosis of the tibia, macrocephaly, or scoliosis
• a first-degree relative with NF1
• Presence of 4 or more cutaneous neurofibromas measuring 0.5-1.2cm in greatest diameter, present on thorax/abdomen or upper or lower limbs;
• If a woman of childbearing potential, is willing to use a medically acceptable form of contraception (in the judgment of the investigator) for the duration of the study;
• Is able to understand the informed consent form describing the risks of this study, and voluntarily signs the informed consent document;
• Is able to understand and comply with the requirements of the protocol.

You may not qualify if:

• Surgical, medical, or investigative treatment for any of the 6 target cutaneous neurofibromas to be evaluated in the study within three months prior to the baseline visit;
• Active infection (bacterial, viral, or fungal) requiring systemic antibiotics within two weeks of the baseline visit;
• Pregnancy or breastfeeding;
• Immunocompromised because of a medical condition;
• Known hypersensitivity to diclofenac or any other NSAID;
• Known hypersensitivity to aspirin;
• has a known hypersensitivity to mannitol, sodium metabisulphite, benzyl alcohol, or propylene glycol;
• Known hypersensitivity to lidocaine;
• Currently receiving or has received with 2 weeks of screening an NSAID (including diclofenac), a COX-2 inhibitor, cyclosporine, methotrexate, an oral anti-diabetic, lithium, digoxin, diuretics, anticoagulants (such as warfarin), or a quinolone antibiotic; except for intralesional diclofenac, these medications will not be allowed during the study; low-dose aspirin used for cardioprotective effects will be allowed;
• Any history of hepatic (including hepatic porphyria) or renal disease resulting in ongoing compromised hepatic or renal function;
• History of a bleeding/coagulation disorder;
• History of gastrointestinal (gastric or intestinal) ulcer disease, Crohn's disease, or ulcerative colitis;
• Laboratory examination at screening that reveals in the opinion of the investigator significant, unstable, and/or untreated renal, hepatic, or metabolic disease/dysfunction;
• White blood cell count at screening that is less than 3000, or a platelet count at screening that is less than 150,000;
• Laboratory evaluation at screening that shows the hemoglobin lower than the lower limit of normal for the laboratory utilized;

Sponsors & Collaborators

• Fundação Educacional Serra dos Órgãos: lead

Study Sites (1)

Fundação Educacional Serra dos Órgãos - UNIFESO

Teresópolis, Rio de Janeiro, 25964-000, Brazil

Location

Related Publications (1)

• Oliveira LB, Geller M, Cunha KS, Santos A, Bernacchi A, Rubenstein AE, Takirambudde S, Mezitis S, de Almeida Ito Brum C, Darrigo LG Jr, Ribeiro MG. Clinical assessment of the use of topical liquid diclofenac following laser microporation of cutaneous neurofibromas in individuals with neurofibromatosis type 1. Heliyon. 2021 Mar 17;7(3):e06518. doi: 10.1016/j.heliyon.2021.e06518. eCollection 2021 Mar.

  PMID: 33817379 DERIVED

MeSH Terms

Conditions

Neurofibromatosis 1

Interventions

Diclofenac; Saline Solution

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Chairman of Immunology and Microbiology

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: March 27, 2017
• Study Start: February 15, 2017
• Primary Completion: March 23, 2017
• Study Completion: June 30, 2017
• Last Updated: October 26, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)