Baricitinib in the Treatment of Kohlmeier-Degos Disease in Patients With Neurological Involvement

Phase 2

Recruiting

• Conditions: Kohlmeier-Degos Disease; Malignant Atrophic Papulosis; Degos Disease; Papulosis, Malignant Atrophic
• Interventions: Drug: Baricitinib

• Registration Number: NCT06923072
• Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary

Background:

Kohlmeier-Degos (KD) is a rare disease that causes inflammation and blood clots, leading to blockages in small blood vessels. These blockages can result in K-D lesions throughout the body, affecting the skin, lungs, heart, spinal cord, and brain. KD can be fatal. No treatment exists for this disease.

Objective:

To test a study drug (baricitinib) in people with brain and spine lesions caused by KD disease. Baricitinib is FDA approved to treat other disorders but has not yet been tried in people with KD.

Eligibility:

People aged 18 years or older with KD-related lesions in the brain and spine.

Design:

Participants will be screened; they will have a physical exam with blood tests. They will also have a baseline visit that may include multiple tests, such as imaging scans of the brain and spine; a lumbar puncture to collect fluid from the spinal canal; and a meeting with a neurologist. They will fill out a questionnaire about their health. They will continue to take their normal medications throughout the study.

Baricitinib is a tablet taken by mouth. Participants will remain on their normal medications for 12 weeks after their baseline visit. Then they will also take the study drug once a day at home for 24 weeks.

Participants will have clinic visits every few weeks for up to 40 weeks. Some visits may take 1 to 4 days. Baseline tests will be repeated 3 more times during study visits. Other visits will require only blood tests; these may be done by local labs that will send the samples to NIH; 2 visits may be done via telehealth....

Detailed Description

Study Description:

This phase II study will provide off-label baricitinib treatment in patients with Kohlmeier Degos disease (K-D) with neurologic involvement. We will perform a baseline research evaluation at the time of enrollment and follow each patient for 12 weeks of background therapy (defined as medications taken by the subject for management of Degos symptoms) followed by 24 weeks of baricitinib treatment (4 mg daily) in addition to background therapy followed by 4 additional weeks of background therapy with final safety assessment at 40 weeks. We will repeat research evaluations at the end of weeks 12, 24, and 36. We will compare the disease progression between weeks 1 through 12 to weeks 13 through 24 as well as weeks 13 through 36. We hypothesize that baricitinib, which targets type I interferon (IFN) and IFN-g signaling, will attenuate various neurological manifestations of K-D that are observed clinically, radiologically or in abnormal laboratory findings in our KD patients. This will help reduce IFN signaling in a manner that may slow or halt the disease progression as measured by the endpoints established below.

Objectives:

Primary Objective:

To test whether baricitinib delays progression of neuroradiological manifestations in patients with neurological involvement of K-D disease.

Secondary Objectives:

To test whether baricitinib treatment improves patient-reported outcomes.

Exploratory Objectives:

* Assess changes in immune cell proportion using single cell Ribonucleic Acid (RNA) sequencing (scRNA-seq) in biospecimens such as skin, cerebrospinal fluid (CSF) and blood after 12 and 24 weeks of baricitinib treatment compared to 12 weeks of just background therapy

* Assess changes in plasma/serum cytokine levels and IFN scores as well as biomarker assays in CSF/blood samples after 12 and 24 weeks of baricitinib treatment compared to 12 weeks of just background therapy.

* To assess whether 12 or 24 weeks of baricitinib treatment will stabilize or improve clinical neurologic exams.

* To assess whether 12 or 24 weeks of baricitinib treatment compared to 12 weeks of just background therapy will reduce the number of new acute K-D skin lesions or slow/halt the progression of existing K-D skin lesions. To assess whether 12 or 24 weeks of baricitinib treatment will reduce the number of new acute K-D skin lesions or slow/halt the progression of existing K-D skin lesions.

Endpoints:

* The primary endpoint will assess the stability of existing enhancing lesions or the lack of development of new enhancing lesions in the brain and spine observed by Magnetic Resonance Imaging (MRI) after 12 or 24 weeks of baricitinib treatment (4 milligrams \[mg\] daily) compared to existing enhancing lesions observed over 12 weeks of background therapy.

* The secondary endpoints will assess the change over 12 and 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy only for the following outcomes: neurological symptoms, self reporting physical functioning, - pain, fatigue, healthrelated questionnaire ( SF-36 ).

* Exploratory endpoints of this study will be clinical and potential surrogate biomarker efficacy data, including:

* Changes in transcriptome/ribonucleic acid (RNA) expression determined by scRNA-seq in skin, CSF and peripheral blood mononuclear cells (PBMCs) after 12 or 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy only.

* Attenuation of plasma/serum cytokine levels and IFN scores as well as biomarkers in assays using CSF and blood samples after 12 and 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy.

* Stability or improvement of motor and/or sensory function on clinical neurologic exams after the 12 or 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy only.

* Changes in the number of new acute K-D skin lesions or slowing/halting progression of existing K-D skin lesions after 12 or 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy only.

Study Timeline

• Study First Submitted: 2025-04-10
• Study First Submitted QC: 2025-04-10
• Study First Posted: 2025-04-11
• Status Verified: 2025-04-21
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-21
• Study Start: 2025-05-26
• Primary Completion: 2030-12-14
• Study Completion: 2030-12-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants with K(SqrRoot)(Delta)hlmeier-Degos Disease receiving Baricitinib	Baricitinib	All participants will take baricitinib 4mg oral daily for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Number of participants with stability of existing enhancing lesions in the brain and/or spine observed in MRI	Baseline, Week 12, Week 24, Week 36	Stability of existing enhancing lesions in the brain and/or spine observed in MRI after 12 or 24 weeks of baricitinib treatment (4 mg daily) as compared to MRI images after 12 weeks of background therapy only.
Number of participants with no new enhancing lesions in the brain and/or spine observed in MRI	Baseline, Week 12, Week 24, Week 36	Lack of development of new enhancing lesions in the brain and/or spine observed in MRI after 12 or 24 weeks of baricitinib treatment (4 mg daily) as compared to MRI images after 12 weeks of background therapy only.

Secondary Outcome Measures

Name	Time	Method
Neurological symptoms using CTCAE	Up to 40 weeks	Compare the change of neurological symptoms using CTCAE over 12 and 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy.
Change in health outcome questionnaire, Short Form-36 (SF-36)	Baseline, Week 12, Week 16, Week 24, Week 36, and up to Week 40	Compare the change in health outcome questionnaire, Short Form-36 (SF-36), over 12 and 24 weeks of baricitinib treatment as compared to 12 weeks of background therapy. This 36-item, patient-reported survey assesses quality of life. It consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States