An Open-label Proof of Concept Study Regarding the Use of Secukinumab (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Mean Score of Participants Who Received Investigator Global Assessment Scores
Study Overview
Brief Summary
This study investigates the efficacy of secukinumab in necrobiosis lipoidica diabeticorum (NLD).
Detailed Description
Necrobiosis lipoidica diabeticorum (NLD) is a rare granulomatous condition of the skin often presenting with papules and eventually atrophic plaques, most commonly on the distal extensor lower extremities, which can be painful and disfiguring. Currently no FDA-approved treatment exists, and no well-established treatment algorithm has been described. Reports on successful therapeutic interventions have generally been small and inconsistent.
Recent literature expanding on the previously poorly understood pathogenesis of NLD has suggested a potential role for IL-17 in the development of this condition. Thus blockade of IL-17 may be a potential therapeutic strategy in patients with NLD. Secukinumab (Cosentyx) is a human monoclonal antibody that targets IL-17a and is FDA approved for the treatment of psoriasis.
This open-label, proof of concept study regarding the use of Secukinumab in patients with NLD may be a first step in elucidating and defining a treatment for this chronic and potentially debilitating condition for which no FDA approved treatment currently exists.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 110 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adults, age 18 and over
- •Previous diagnosis of biopsy-proven NLD
- •Active NLD lesions, defined as
- •clinical signs of inflammation, for example erythematous margins, sensations of itch, pain, dysaesthesia
- •lesions increasing in size or appearance of new lesions within the last 3 months
- •ulcerations
- •Subjects must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed.
Exclusion Criteria
- •History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test at screening.
- •Are currently pregnant, breastfeeding, or planning to get pregnant during the study.
- •Previous hypersensitivity reaction to secukinumab or to any of the components.
- •History of Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis)
- •Allergy to Latex
- •Currently on any other immunosuppressant systemic medication or within 28 days of baseline visit
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the study and for 16 weeks after stopping treatment.
- •Subjects with a serum creatinine level exceeding 176.8 μmol/L (2.0 mg/dL)
- •Screening total WBC count <2,500/μL, or platelets <100,000/μL or neutrophils <1,500/μL or hemoglobin <8.5 g/dL
- •Known infection with HIV, hepatitis B or hepatitis C at screening or randomization. Patients who are Hepatitis B Core antibody and/or Hep B Surface Antigen positive will be excluded from this study. Patients who are Hepatitis C ab positive will also be excluded from this study.
- •History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for non-melanoma skin cancer and carcinoma in situ of the cervix)
- •Are participating in another study using an investigational agent or procedure during participation in this study or within 28 days prior to baseline visit.
- •Plans for administration of live vaccines during the study period or 6 weeks prior to randomization
- •Any other procedural treatment for NLD with 28 days prior to baseline visit, including phototherapy, surgical intervention, laser therapy, or cryotherapy.
- •Any other active skin disease or condition (e.g., bacterial, fungal or viral infection) that may interfere with assessment of NLD;
- •Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy
Arms & Interventions
Secukinumab Subcutaneous Injection
300 mg q weekly for 5 weeks followed by 300 mg q 4 weeks.
Each subject will receive 300mg of Secukinumab by using 2 syringes of 150mg each as a subcutaneous injection at weeks 0,1,2,3,4 then every 4 weeks for a total of 9 doses over 24 weeks.
Intervention: Secukinumab (Drug)
Outcomes
Primary Outcomes
Mean Score of Participants Who Received Investigator Global Assessment Scores
Time Frame: 24 weeks
Number of patients who received Investigator Global Assessment Scores rating their remission or clinical improvement as measured at week 24. The minimum score is zero and the maximum score is 6. A larger score is worse. Score Descriptions: 0. Completely clear: except for possible residual hyperpigmentation 1. Almost clear: very significant clearance (about 90%); however, patchy remnants of dusky erythema and/or very small ulcerations 2. Marked improvement: significant improvement (about 75%); however, a small amount of disease remaining (i.e. remaining ulcers, although have decreased in size, minimal erythema and/or active boarder) 3. Moderate improvement: intermediate between slight and marked; representing about 50% improvement 4. Slight improvement: some improvement (about 25%); however, significant disease remaining (i.e. remaining ulcers with only minor decrease in size, erythema or boarder activity) 5. No change from baseline 6. Worse
Secondary Outcomes
- Histology(26 weeks)
- Pain Score Baseline and Week 24(Baseline and Week 24)
- Dermatology Life Quality Index(Baseline and Week 24)
Investigators
Martina Porter
Assistant Professor of Dermatology
Beth Israel Deaconess Medical Center