Secukinumab for NLD (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)
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|ClinicalTrials.gov Identifier: NCT03791060|
Recruitment Status : Suspended (Enrollment and other trial activities have temporarily paused due to COVID-19 and are expected to resume in the future; This is not a suspension of IRB approval)
First Posted : January 2, 2019
Last Update Posted : April 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|Necrobiosis Lipoidica Diabeticorum||Drug: Secukinumab||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label Proof of Concept Study Regarding the Use of Secukinumab (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)|
|Actual Study Start Date :||April 3, 2019|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||September 2021|
Experimental: 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.
Secukinumab is selective for human IL-17A and potently neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine in multiple autoimmune and inflammatory processes. It is being recognized as one of the principal pro-inflammatory cytokines in autoimmune diseases such as psoriasis, PsA and AS, uveitis and is thought to play a role in other inflammatory conditions.
Other Name: cosentyx
- Investigator Global Assessment Score [ Time Frame: 24 weeks ]
Proportion of patients achieving remission or clinical improvement based on Investigator Global Assessment Score as measured at week 24.
0. Completely clear: except for possible residual hyperpigmentation
- Almost clear: very significant clearance (about 90%); however, patchy remnants of dusky erythema and/or very small ulcerations
- 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)
- Moderate improvement: intermediate between slight and marked; representing about 50% improvement
- Slight improvement: some improvement (about 25%); however, significant disease remaining (i.e. remaining ulcers with only minor decrease in size, erythema or boarder activity)
- No change from baseline
- Histology [ Time Frame: 26 weeks ]
Proportion of subjects achieving improvement based upon histological score. The score is calculated by adding subscores as listed below, which will be evaluated by the dermatopathologist. Average of pre and post scores and overall change in score will be calculated and compared using a paired T-test.
- Inflammatory infiltrate (0, none; 1, slight; 2, moderate; 3, severe)
- collagen degeneration (0, none; 1, slight; 2, moderate; 3, severe)
- epithelioid histiocytes, (0, none; 1, slight; 2, moderate; 3, severe)
- qualitative expression of IL-17 (0, none; 1, slight; 2 moderate; 3, severe)
- Pain Score [ Time Frame: Assessed at week 1, 2, 3, 4, 8, 12, 16, 20, 25 ]
Self-reported pain and stinging intensity during and directly after treatment with Secukinumab injections
A Pain Score will be calculated based upon the Wong-Baker 10-point pain score, which has been widely used to rate pain in both children and adults and has also been used in dermatology clinical trials.
Response based on an improvement from baseline in the Wong-Baker pain score at all scheduled time points will be calculated. We will compare pre and post treatment pain values and categorize patients as (i) Resolved (ii) Improved (iii) Stable (iv) Worsened
- Dermatology Life Quality Index [ Time Frame: Assessed at week 1, 2, 3, 4, 8, 12, 16, 20, 25 ]Proportion of subjects improving based upon patient-reported outcomes The DLQI is a validated general dermatology questionnaire that consists of 10 items that assess subject health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment) The DLQI is a psychometrically valid and reliable instrument that has been translated into several languages, and the DLQI total scores have been shown to be responsive to change. The minimally important difference for the DLQI has been estimated as a 2 to 5 point change from baseline.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03791060
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Alexa Kimball, MD MPH||Beth Israel Deaconess Medical Center|