Contact a Trial Coordinator for more information on our trials.
18 years to 80 years
At least 6 weeks prior to Baseline.
- Male or female patients age 18 to 80 years of age, inclusive, at Screening.
- Biopsy-confirmed diagnosis of NL. Biopsies of continually active lesions performed outside of this clinical study will need to be reviewed and the diagnosis confirmed by the study pathologist. For patients with no previous history of biopsy, no biopsy within the previous 5 years, a biopsy that is not confirmed to be NL, or newly active lesion, a biopsy to confirm a diagnosis of NL will be performed at the Screening visit.
- Reference NL lesion with a score of 2 or greater on the Investigator Global Assessment: Necrobiosis Lipoidica (IGA:NL) Activity scale AND surface area with minimum size of 10 cm2. If more than one lesion is present, the reference lesion area is the lesion with the highest disease severity.
- Current or previous (within 4 weeks of Baseline) treatment with:
- Oral, topical, or intralesional corticosteroids;
- Systemic pentoxifylline, theophylline, or cilostazol
- Oral or topical retinoid;
- Other systemic or topical immunosuppressant drugs, including but not limited to calcineurin inhibitors (e.g., tacrolimus), thalidomide, apremilast, anti-malarials (e.g., hydroxychloroquine, chloroquine), cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, etc.
- Current or previous (within 12 weeks of Baseline) treatment with any biologic therapy (e.g., adalimumab, etanercept, infliximab, anakinra, etc.).
- Phototherapy/photochemotherapy (NBUVB, UVB, PUVA) within 6 weeks prior to Baseline
- Skin grafting, or other surgical procedure (other than debridement) within 6 weeks prior to Baseline.
- History of drug allergy, including but not limited to pentoxifylline or other xanthine derivatives, or other allergy, which in the opinion of the Investigator, contraindicates participation.
- Anticipated concurrent use of a strong CYP1A2 inhibiting drug, including but not limited to cimetidine and/or fluvoxamine, during the course of the study (after Screening).
- Fever (>38°C), or chronic, persistent, or recurring infection(s) at Screening or Baseline.
- Any infection requiring oral antimicrobial therapy within 2 weeks prior to Baseline or any infection requiring parenteral antibiotics or hospitalization within 12 weeks prior to Baseline. Any treatment for such infections must have been completed and the infection cured for at least 2 weeks prior to Baseline.
- History of sarcoidosis, pyoderma gangrenosum, or any other disorder (in the judgment of the Investigator) that would interfere with the evaluation of NL or require protocol prohibited medication.
- History of any life threatening infection or sepsis within 12 months of Baseline:
- Clinically significant cardiac disease including but not limited to unstable angina, acute myocardial infarction within 6 months of Baseline, and arrhythmia requiring therapy.
- Patient has QTc interval ≥ 480 milliseconds on Screening Electrocardiogram (ECG); a second Screening ECG may be done at investigator's discretion but the average of the two QTc screening intervals must not be ≥ 480 milliseconds. History of cerebral hemorrhage, cerebrovascular accident, transient ischemic attack, gastrointestinal bleeding, or retinal hemorrhage within 6 months of Baseline.
- History of cerebral hemorrhage, cerebrovascular accident, transient ischemic attack, gastrointestinal bleeding, or retinal hemorrhage within 6 months of Baseline.
- Patient has active or history of neoplastic disease (except for adequately treated non-invasive basal cell and/or squamous cell carcinoma or carcinoma in situ of the cervix) within the past 5 years prior to Baseline.
- Presence of clinically significant medical condition(s) including but not limited to: renal, hepatic, cardiovascular, hematological, gastrointestinal, endocrine, pulmonary, neurological, psychiatric, substance abuse, and/or any other clinically significant disease or disorder, which in the opinion of the Investigator (by its nature or by being inadequately controlled), may put the patient at risk due to participation in the study, influence the results of the study, and/or affect the patient's ability to complete the study.
- History of or current diagnosis of active tuberculosis (TB); undergoing treatment for latent TB infection (LTBI); untreated LTBI (as determined by documented results within 3 months of the Screening Visit of a positive TB skin test with purified protein derivative with induration >= 5 millimeter (mm), or a positive QuantiFERON-TB test or positive or borderline T-Spot [Elispot] test); or positive TB test at Screening. Subjects with documented completion of appropriate LTBI treatment would not be excluded and are not required to be tested.
- Vaccination with live or live-attenuated virus vaccine within 1 month prior to Baseline.
- The results of the following laboratory tests performed at the central laboratory at Screening meet any of the criteria below:
- Hemoglobin < 8.0 g/dL (International System of Units (SI): < 80 g/L);
- White blood cells < 3.0 x 10^3 cells/mm^3 (SI: < 3.0 x 10^9 cells/L);
- Neutrophils < 1.0 x 10^3 cells/mm^3 (SI: < 1.0 x 10^9 cells/L);
- Lymphocytes < 0.5 x 10^3 cells/mm^3 (SI: < 0.5 x 10^9 cells/L);
- Platelets < 100 x 10^3 cells/mm^3 (SI: < 100 x 10^9 cells/L)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkaline phosphatase (ALP) ≥ 2 x upper limit of normal (ULN);
- Total bilirubin level ≥ 2 x ULN unless the individual has been diagnosed with Gilbert's disease and this is clearly documented;
- Estimated glomerular filtration rate < 40 mL/min/1.73 m^2 based on the Modification of Diet in Renal Disease (MDRD) formula.
- Positive HIV serology
- Evidence of active Hepatitis B Virus (HBV) infection
- Evidence of active Hepatitis C Virus (HCV) infection
- Women who are pregnant or breastfeeding.
- Patient unwilling or unable to swallow tablets whole.
- Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study.
- Use of any investigational product within 30 days prior to Baseline or currently enrolled in another study that involves clinical investigations.
Enrollment and Locations
For more information on enrollment in our current clinical trials, please visit clinicaltrials.gov for location information.
About Necrobiosis Lipoidica
Necrobiosis lipoidica (NL) is a chronic, disfiguring condition affecting the skin and tissue under the skin typically on the lower extremities with no currently approved FDA treatments. More severe complications can occur, such as deep tissue infections and osteonecrosis threatening life of the limb.
Approximately 22,000 – 55,000 people in the United States and more than 200,000 – 500,000 people outside the United States are affected by NL with the prevalence of open ulcers being approximately 30% of all NL patients.
The degeneration of tissue occurring at the NL lesion site is caused by a number of pathophysiological changes which has made it extremely difficult to develop effective treatments for this condition. At this time there is no approved FDA treatment for NL and PCS499 could be the first drug approved. PCS499 and its metabolites affect a number of biological pathways, several of which contribute to the pathophysiology associated with NL.
Frequently Asked Questions
What is a clinical trial?
A Clinical Trial is a type of research study that examines how well a potential therapy works in humans.
Why was this trial done?
This is an open-label study that will evaluate the safety of PCS499 for the treatment of necrobiosis lipoidica (NL) and will inform the design of future studies. Approximately 12 NL patients (6-9 patients without ulceration and 3-6 patients with ulceration) who also meet other inclusion/exclusion criteria will be enrolled in the study. The primary objective of this study is to evaluate the safety and tolerability profile of PCS499 in patients with Necrobiosis Lipoidica.
Who sponsored this trial?
Processa Pharmaceuticals, Inc. sponsored this clinical trial.
How many people participated in this trial?
A total of 12 patients were enrolled in this clinical trial.
The safety and efficacy of the investigational use of this product have not been determined. There is no guarantee that the investigational use listed will be filed with and/or approved for marketing by a regulatory agency.