Necrobiosis Lipoidica DiabeticorumPhase 2NCT03791060

Secukinumab for NLD (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)

A Phase 2 study testing Secukinumab in people with Necrobiosis Lipoidica Diabeticorum, run by Beth Israel Deaconess Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study investigates the efficacy of secukinumab in necrobiosis lipoidica diabeticorum (NLD). Read more about this study

Who is it for?: Ages 18 to 110 years
Conditions the study is for: Necrobiosis Lipoidica Diabeticorum
What is being tested?: Secukinumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 1 siteUnited States
Study dates: 3 Apr 2019to 10 Apr 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 110 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 16Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: An Open-label Proof of Concept Study Regarding the Use of Secukinumab (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)

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

Read the 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.

Conditions: Necrobiosis Lipoidica Diabeticorum
Being tested: Secukinumab
Keywords: Necrobiosis lipoidica, NLD
Medical subject headings: Necrobiosis Lipoidica

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SecukinumabDrug
Also called cosentyx
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.

Study groups in NCT03791060
Study group	Role	What they receive
Secukinumab Subcutaneous Injection	Experimental	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. Receives: Drug: Secukinumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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:
1. Completely clear: except for possible residual hyperpigmentation
2. Almost clear: very significant clearance (about 90%); however, patchy remnants of dusky erythema and/or very small ulcerations
3. 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)
4. Moderate improvement: intermediate between slight and marked; representing about 50% improvement
5. Slight improvement: some improvement (about 25%); however, significant disease remaining (i.e. remaining ulcers with only minor decrease in size, erythema or boarder activity)
6. No change from baseline
7. Worse
Measured: 24 weeks

Secondary outcomes (3)

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.
1. Inflammatory infiltrate (0, none; 1, slight; 2, moderate; 3, severe)
2. collagen degeneration (0, none; 1, slight; 2, moderate; 3, severe)
3. epithelioid histiocytes, (0, none; 1, slight; 2, moderate; 3, severe)
4. qualitative expression of IL-17 (0, none; 1, slight; 2 moderate; 3, severe)
Histologic analysis not performed as study was terminated prematurely.
Measured: 26 weeks
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
Measured: Baseline and Week 24
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.
Measured: Baseline and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Apr 201910 Apr 2021

First posted2 Jan 2019
Study start3 Apr 2019
Primary completion17 Jan 2021
Study completion10 Apr 2021

Why it stopped: Study halted prematurely due COVID-19 pandemic and did not resume; participants are no longer being examined or receiving intervention.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Necrobiosis Lipoidica DiabeticorumStudies of the same condition, open and under way.
More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03791060
Sponsor's protocol ID: 2018P000634
Status last verified: May 2024
First submitted: 21 Dec 2018
Last updated: 17 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label Proof of Concept Study Regarding the Use of Secukinumab (Cosentyx) in Patients With Necrobiosis Lipoidica Diabeticorum (NLD)
ClinicalTrials.gov ID: NCT03791060
Acronym / sponsor ID: 2018P000634
Conditions: Necrobiosis Lipoidica Diabeticorum
Keywords: Necrobiosis lipoidica, NLD
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study halted prematurely due COVID-19 pandemic and did not resume; participants are no longer being examined or receiving intervention.
Enrolment: 4 participants (actual)
Lead sponsor: Beth Israel Deaconess Medical CenterUniversity, hospital or other
Collaborators: Novartis Pharmaceuticals
Study start: 3 Apr 2019 (actual)
Primary completion: 17 Jan 2021 (actual)
Study completion: 10 Apr 2021 (actual)
First posted: 2 Jan 2019 (actual)
Results: Posted 17 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Secukinumab Subcutaneous Injection	Experimental	Drug: Secukinumab300 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.

Who may qualify

Ages: 18 to 110 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Adults, age 18 and over
Previous diagnosis of biopsy-proven NLD
Active NLD lesions, defined as
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.

Key exclusion criteria (16 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SecukinumabAlso: cosentyxSecukinumab 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.	Drug	Secukinumab Subcutaneous Injection

Primary outcome

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

3 secondary outcomes

Histology
Time frame: 26 weeks
Pain Score Baseline and Week 24
Time frame: Baseline and Week 24
Dermatology Life Quality Index
Time frame: Baseline and Week 24

Results and safety

Results posted to the registry on 17 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Secukinumab Subcutaneous Injection	4	3

Primary outcome: Mean Score of Participants Who Received Investigator Global Assessment Scores

Time frame: 24 weeks. Mean (Standard Deviation). Unit: score on a scale

Measure	Secukinumab Subcutaneous Injection n = 4
Value	4 (0.81)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: At every visit adverse events will be registered for 36 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Secukinumab Subcutaneous Injection	0 of 4 (0%)	0 of 4 (0%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alexa Kimball, MD MPH principal investigator

Beth Israel Deaconess Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Secukinumab in people with Necrobiosis Lipoidica Diabeticorum, run by Beth Israel Deaconess Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Score of Participants Who Received Investigator Global Assessment Scores (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03791060.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.