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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03791060
Other study ID # 2018P000634
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
Start date April 3, 2019
Est. completion date April 10, 2021

Study information

Verified date May 2024
Source Beth Israel Deaconess Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study investigates the efficacy of secukinumab in necrobiosis lipoidica diabeticorum (NLD).


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.


Recruitment information / eligibility

Status Terminated
Enrollment 4
Est. completion date April 10, 2021
Est. primary completion date January 17, 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years to 110 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Secukinumab
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.

Locations

Country Name City State
United States Beth Israel Deaconess Medical Center Boston Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Beth Israel Deaconess Medical Center Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Mean Score of Participants Who Received Investigator Global Assessment Scores 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
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
Worse
24 weeks
Secondary Histology Number 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)
Histologic analysis not performed as study was terminated prematurely.
26 weeks
Secondary Pain Score Baseline and Week 24 Number of patients who completed the 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 Faces Pain rating Scale (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.
Scale score 0-10, higher score means worse outcome:
0 = No hurt 2 = Hurts a little bit 4 = Hurts a little bit more 6 = Hurts even more 8 = Hurts whole lot 10 = Hurts worst 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
Baseline and Week 24
Secondary Dermatology Life Quality Index Number of subjects improving based upon patient-reported outcomes The Dermatology Life Quality Index (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 scoring of each question is as follows:
Very much scored = 3 points, A lot scored = 2 points, A little scored = 1, Not at all scored = 0 points, Not relevant scored = 0 points, Question 7, 'prevented work or studying' scored = 3 points. The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 (meaning maximum impact on quality of life) and a minimum of 0 (meaning no impact of skin disease on quality of life). The higher the score, the more quality of life is impaired.
0-1 = No effect on patient's life, 2-5 = Small effect, 6-10 = Moderate effect, 11-20 = Very large effect, 21-30 = Extremely large effect.
Baseline and Week 24