Clinical trial NCT04186559: Topical Pentoxifylline Gel on Behcet's Disease Genital Ulcers
Official title: Clinical Protocol to Evaluate Use of Topical Pentoxifylline Gel on Behcet's Disease Genital Ulcers
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Behcet Syndrome
Behcet Disease
Lead sponsor: Silk Road Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2019-12-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Behçet's Disease (BD) is a complex, chronic, relapsing, multi-system inflammatory disorder that is characterized by oral ulcers, genital ulcers in addition to ocular and skin symptoms. Genital ulcers are the second most common symptom of BD and occur in 57-93% of BD patients. The genital ulcers of BD clearly cause considerable morbidity for those affected. This will be one of the first trials of a topical product designed for accelerated healing of BD genital ulcers. There is no cure or FDA-approved therapies for BD genital ulcers and the treatment of recurrent genital ulcers that are associated with BD is palliative.

Recent study evaluating the effect of topical PTX on BD oral ulcers suggests that topical pentoxifylline (PTX) might have an immediate impact on BD oral ulcer healing leading to accelerated ulcer clearance, which results in lower daily ulcer numbers for the patients along with reduced pain scores. Investigators hypothesize that application of topical PTX will accelerate the healing of BD genital ulcers in a similar clinically meaningful way, and further hypothesize that topical PTX can become a valuable adjunct to any other systemic therapy for BD.

Detailed description: In contrast to the recent study on BD oral ulcers, in which very carefully selected patients were enrolled (i.e. no immunosuppressive therapies and a new lesion of no more than 48hrs), this trial will be more "Real World" and enroll all patients with genital ulcers of BD, allowing randomization to eliminate biases between treatment and control groups. The advantages of this more open approach are twofold. First, this approach more directly measures the benefit of PTX gel therapy on the population that is more likely to use the therapy if it becomes approved. Secondly, those broader criteria will allow faster enrollment for a disease manifestation that occurs considerably less frequently than oral ulcers.

This randomized proof of concept trial investigating the effect of topical PTX on BD genital ulcers will be double-blind, placebo controlled with a crossover component, and it will follow the patients during the treatment period of 30 days or until the healing of genital ulcers. Specifically, patients who receive placebo as their initial course of treatment would receive active drug in a second course of treatment in which they would be re-enrolled upon recurrence of another crop of genital ulcers. Conversely, patients who receive active drug in their initial course of treatment would receive placebo drug once they are re-enrolled for the second course of treatment.

For all patients in either group, investigators will collect photographs of the external genital ulcer area, the size and location of the genital ulcers, number of ulcers, pain scores, and concomitant medications. This data will be collected for the following month or until the healing of genital ulcers. Additionally, adverse event experiences will be solicited. Data analyses will be exploratory comparisons of differences in safety and efficacy endpoints between BD patients who did and did not receive topical PTX.

Eligibility criteria: Inclusion Criteria:

* Meets the International Study Group criteria for Behcet's Disease (BD)
* Presents with at least one active genital lesion accessible to measurement
* Adult (\>18 years) male or a non-pregnant, non-lactating female
* Has signed an IRB approved subject consent form
* Has completed all screening procedures satisfactorily, is deemed to be an acceptable subject and is otherwise eligible for entry into the study
* Is willing and able to comply with the protocol
* Subject's treating physician confirm that the subject has previously had a genital ulcer due to Behcet's Disease

Exclusion Criteria:

* Has a severe, acute, or chronic systemic disease other than BD such as congestive heart failure, hepatic failure, renal failure, systemic lupus erythematosus, Stevens- Johnson syndrome, ulcerative colitis, cancer, leukemia, diabetes, AIDS, or any other condition for which they are immune-compromised
* Has received PTX in any form over the previous 5 days prior to enrollment
* Has a history of, or is currently exhibiting, any disease or condition, which, in the opinion of the principal investigator, would place the subject at increased risk during study therapy
* Has experienced recent cerebral and/or retinal hemorrhage or in patients who have previously exhibited intolerance to this product or methylxanthines such as caffeine, theophylline, and theobromine
* Is receiving apremilast or anti-TNF agents such as; Rituximab, Infliximab, Adalimumab, Etanercept (azathioprine, cyclosporine, colchicine, mycophenolate mofetil, interferon and topical or systemic steroid use does not disqualify from enrollment- however, topical steroids should not be used during the treatment period)
* Has concomitant administration of strong CYP1A2 inhibitors (including e.g. ciprofloxacin or fluvoxamine) and other drugs that may increase the exposure to PTX

Primary outcomes:
measure: Mean time to healing of genital ulcers
timeFrame: The participants will be assessed at thirteen time points (or until the complete healing of genital ulcers) for each treatment period. Each treatment period is estimated to take 30 days.There will be a final follow-up 30 days after the treatment.
measure: Mean change in total number of genital ulcers
timeFrame: The participants will be assessed at thirteen time points (or until the complete healing of genital ulcers) for each treatment period. Each treatment period is estimated to take 30 days.There will be a final follow-up 30 days after the treatment.
measure: Mean change in patient reported outcome pain scores in numeric rating scale
timeFrame: The participants will be assessed at thirteen time points (or until the complete healing of genital ulcers) for each treatment period. Each treatment period is estimated to take 30 days. There will be a final follow-up 30 days after the treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Silk Road Therapies
state: District of Columbia
Study officials:
affiliation: Shores Rheumatology
name: Andew J Sulich, MD
role: PRINCIPAL_INVESTIGATOR
References: