Baricitinib for Malignant Atrophic Papulosis

Overseen By William R Whalen, C.R.N.P.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Disqualifiers: Active infection, Low hemoglobin, Low platelets, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 43

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests baricitinib, a medication, for treating brain and spine lesions caused by Kohlmeier-Degos disease (KD), a rare condition that leads to inflammation and blood clots in small blood vessels. Although baricitinib is approved for other conditions, it has not been used for KD before. Suitable candidates for this trial are those 18 or older who have been diagnosed with KD and have lesions in their brain or spine. Participants will take baricitinib daily at home for 24 weeks while continuing their regular medications. Regular clinic visits will monitor the treatment's effects over approximately 40 weeks. As a Phase 2 trial, this research measures how well baricitinib works for KD in an initial, smaller group of people, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants will continue their normal medications throughout the study.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Previous studies have shown that baricitinib works well for other conditions. The FDA has approved it for some diseases, indicating a history of safety. Research shows that patients generally tolerate baricitinib well, with some studies noting manageable side effects. For instance, patients treated with baricitinib have experienced improvements without major negative effects.

Although using baricitinib for Kohlmeier-Degos (KD) disease is new, its approval for other conditions offers some reassurance about its safety. This trial is in the early stages and aims to assess the safety and tolerability of baricitinib for people with KD-related brain and spine issues. Researchers will closely monitor participants to quickly identify and manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Baricitinib is unique because it targets the Janus kinase (JAK) pathway, which plays a key role in immune response and inflammation. Unlike current treatments for Malignant Atrophic Papulosis, which primarily focus on symptom management, Baricitinib offers a more targeted approach by potentially modulating the underlying immune mechanisms of the disease. Researchers are excited about Baricitinib because it promises a novel way to address the condition at its source, offering hope for more effective and lasting relief.

What evidence suggests that baricitinib might be an effective treatment for Kohlmeier-Degos disease?

Research has shown that baricitinib can reduce inflammation and slow disease progression in conditions similar to Kohlmeier-Degos disease. One study found that patients taking baricitinib had lower blood inflammation levels, even months after stopping the drug. Baricitinib blocks proteins that cause inflammation, which is crucial for treating diseases where blood vessels are blocked, like KD. Although baricitinib is already used for other diseases, its ability to reduce inflammation suggests it might help with KD-related issues in the brain and spine. Early results are promising, but further research is needed to confirm its effectiveness for KD. Participants in this trial will receive baricitinib to evaluate its potential benefits for KD. ^{1 2 3 4 6}

Who Is on the Research Team?

Cornelia D Cudrici, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Kohlmeier-Degos Disease who have lesions in the brain and spine. Participants must be able to undergo various tests, including imaging scans and lumbar punctures, and fill out health questionnaires. They should continue their normal medications during the study.

Inclusion Criteria

Ability of subject or LAR to understand and the willingness to sign a written informed consent document

Provision of signed and dated informed consent form by the subject or Legally Authorized Representative (LAR)

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

Hemoglobin <7 g/dL

Platelet counts < 50 K /mcL

Neutropenia (ANC <0.5 x k/mcL)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation

Participants undergo baseline evaluations including imaging scans, lumbar puncture, and health questionnaires

1 week

1 visit (in-person)

Background Therapy

Participants continue their normal medications for management of Degos symptoms

12 weeks

Visits every few weeks, some may be virtual

Baricitinib Treatment

Participants take baricitinib 4mg daily in addition to background therapy

24 weeks

Clinic visits every few weeks, some visits may take 1 to 4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Final safety assessment at 40 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview The trial is testing Baricitinib, a drug approved for other conditions but not yet for KD disease with neurological involvement. Over a period of up to 40 weeks, participants will take Baricitinib daily while continuing their regular treatments.

How Is the Trial Designed?

Group I: Participants with K(SqrRoot)(Delta)hlmeier-Degos Disease receiving Baricitinib Experimental Treatment 1 Intervention

All participants will take baricitinib 4mg oral daily for 24 weeks.

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a preliminary study involving four patients with progressing vitiligo, treatment with oral baricitinib for 12 weeks resulted in significant re-pigmentation without major side effects, indicating its efficacy and safety.

In laboratory tests, baricitinib enhanced tyrosinase activity and melanin production in damaged melanocytes, suggesting a mechanism of action that could help restore pigmentation in vitiligo patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro. Dong, J., Huang, X., Ma, LP., et al.[2022]

Baricitinib, an oral JAK1/JAK2 inhibitor, has a safety profile that reflects the inherent risks of the diseases it treats, with higher rates of infections and serious adverse events observed in patients with rheumatic diseases compared to those with dermatological conditions.

In clinical studies, the incidence of major adverse cardiovascular events (MACE) with baricitinib was lower than that seen with tofacitinib and comparable to tumor necrosis factor inhibitors, indicating a favorable safety profile, especially in hospitalized COVID-19 patients treated for up to 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. Bieber, T., Feist, E., Irvine, AD., et al.[2023]

In the BRAVE-AA1 and BRAVE-AA2 phase III trials, 69% of patients treated with baricitinib 4 mg and 51% with 2 mg achieved at least a 30% improvement in hair regrowth (SALT30) by week 52, indicating the efficacy of baricitinib in treating severe alopecia areata.

The study identified three responder subgroups based on the timing of achieving SALT30: early (by week 12), gradual (between weeks 12-36), and late (after week 36), with early responders showing the best outcomes, particularly among patients with less severe baseline alopecia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When to expect scalp hair regrowth during treatment of severe alopecia areata with baricitinib: insights from trajectories analyses of patients enrolled in two phase III trials. King, B., Shapiro, J., Ohyama, M., et al.[2023]

In a case series involving 6 patients with treatment-resistant inflammatory skin conditions, the JAK inhibitors upadacitinib and tofacitinib showed promising clinical outcomes, including symptom resolution and reduced flares in conditions like dermatomyositis and hidradenitis suppurativa.

These findings suggest that JAK inhibitors may serve as effective off-label treatments for various inflammatory cutaneous disorders, warranting further research with larger patient groups to confirm their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases. Agarwal, A., Diaz, A., Al-Dehneem, R., et al.[2023]

In a Phase 3 trial with 329 patients suffering from moderate-to-severe atopic dermatitis, baricitinib (4-mg and 2-mg) combined with topical corticosteroids showed significant improvements in health-related quality of life (HRQoL) and work productivity starting as early as Week 2.

Baricitinib 4-mg maintained these improvements through Week 16, demonstrating its efficacy in reducing symptoms and enhancing overall treatment benefits compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. Wollenberg, A., Nakahara, T., Maari, C., et al.[2021]

Baricitinib, a JAK1-2 inhibitor approved for moderate-to-severe atopic dermatitis, has a safety profile where infections are the most common side effects, primarily mild-to-moderate cases like upper respiratory infections and herpes simplex exacerbations.

The analysis included data from eight clinical trials, highlighting the need for more real-world data to better understand which patients may benefit most from baricitinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious adverse events in patients with atopic dermatitis treated with baricitinib. Antonelli, F., Malvaso, D., Caldarola, G., et al.[2023]

Citations

1. academic.oup.com academic.oup.com/bjd/article/193/1/180/8092546

Rescue therapy in malignant atrophic papulosis: a new era of ... Five months after stopping baricitinib, the blood IGS score remains low (2.7 vs. 6.1). (a) Papules with atrophic porcelain white centre and ...

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=002416-H&&query=2%20Multiple

Protocol Details Background: Kohlmeier-Degos (KD) is a rare disease that causes inflammation and blood clots, leading to blockages in small blood vessels.

3. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(22)00167-3/fulltext

Interferon receptor dysfunction in a child with malignant ... Treatment with baricitinib and anifrolumab effectively slowed disease progression. A randomised controlled trial of baricitinib or anifrolumab, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06923072

Baricitinib in the Treatment of Kohlmeier-Degos Disease ... Background: Kohlmeier-Degos (KD) is a rare disease that causes inflammation and blood clots, leading to blockages in small blood vessels.

5. withpower.com withpower.com/trial/phase-2-atrophy-3-2025-5febd

Baricitinib for Malignant Atrophic Papulosis Baricitinib, a drug that blocks certain proteins involved in inflammation, has shown effectiveness in treating various skin conditions and inflammatory diseases ...

6. go.drugbank.com go.drugbank.com/drugs/DB11817/clinical_trials?conditions=DBCOND0005722&phase=2&purpose=treatment&status=recruiting

Baricitinib Recruiting Phase 2 Trials for Malignant Atrophic ... Baricitinib Recruiting Phase 2 Trials for Malignant Atrophic Papulosis Treatment ; NCT06923072. Baricitinib in the Treatment of Kohlmeier-Degos Disease in ...