Clinical trial NCT03791060: Secukinumab for NLD (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)
Official title: An Open-label Proof of Concept Study Regarding the Use of Secukinumab (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Necrobiosis Lipoidica Diabeticorum
Keywords: Necrobiosis lipoidica
NLD
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2019-01-02
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Score of Participants Who Received Investigator Global Assessment Scores
timeFrame: 24 weeks
Secondary outcomes:
measure: Histology
timeFrame: 26 weeks
measure: Pain Score Baseline and Week 24
timeFrame: Baseline and Week 24
measure: Dermatology Life Quality Index
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Alexa Kimball, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: