Baricitinib for Malignant Atrophic Papulosis

Overseen By Cornelia D Cudrici, M.D.

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

Trial Summary

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.

What data supports the effectiveness of the drug Baricitinib for treating Malignant Atrophic Papulosis?

Baricitinib, a drug that blocks certain proteins involved in inflammation, has shown effectiveness in treating various skin conditions and inflammatory diseases, such as atopic dermatitis and other immune-related skin disorders. This suggests it might help with conditions like Malignant Atrophic Papulosis, which also involve inflammation. ^{1 2 3 4 5}

Is baricitinib generally safe for humans?

Baricitinib has been studied for various conditions like rheumatoid arthritis, atopic dermatitis, and COVID-19, and is generally considered safe. Common side effects include mild-to-moderate infections, such as upper respiratory tract infections and herpes simplex. Serious infections and other adverse events like cardiovascular issues are more common in patients with existing risk factors. ^{2 5 6 7 8}

How is the drug Baricitinib unique for treating Malignant Atrophic Papulosis?

Baricitinib is unique because it is a Janus kinase (JAK) inhibitor, which means it works by blocking specific enzymes involved in inflammation and immune responses. This mechanism is different from other treatments, as there are no standard treatments specifically for Malignant Atrophic Papulosis, making Baricitinib a novel option for this condition. ^{2 3 5 9 10}

What is the purpose of this trial?

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....

Research Team

Cornelia D Cudrici, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Off-Label Use of Baricitinib in Dermatology. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

BRAF Inhibitors for the Treatment of Papulopustular Eruptions from MAPK Pathway Inhibitors. [2021]

5. England 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Infectious adverse events in patients with atopic dermatitis treated with baricitinib. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Baricitinib Safety for Events of Special Interest in Populations at Risk: Analysis from Randomised Trial Data Across Rheumatologic and Dermatologic Indications. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Baricitinib is Effective in Treating Progressing Vitiligo in vivo and in vitro. [2022]

10. England 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. [2023]