NCT07262983

Evaluating the Safety and Tolerability of Baricitinib in Patients With Job Syndrome With Lupus-Like Disease and/or Atopic Dermatitis

A Pilot Study to Evaluate the Safety and Tolerability of Baricitinib in Patients With Job s Syndrome With Lupus-like Disease and/or Atopic Dermatitis

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 12 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: Autosomal dominant hyper-IgE syndrome (HIES), also called Job syndrome, is a genetic disorder that affects the immune system. It can cause skin and lung infections and problems with blood vessels, connective tissues, and bones. People with HIES often have lupus-like disease or atopic dermatitis (skin rash). Researchers want to know if a drug approved to treat other immune system diseases (baricitinib) can help people with HIES. Objective: To test baricitinib in people with HIES with lupus-like disease or skin rash. Eligibility: People aged 12 years and older with HIES with lupus-like disease or skin rash. Design: Participants will have 5 clinic visits, 4 remote visits, and 2 phone visits in 9 months. Participants will be screened. They will have a physical exam with blood and urine tests. They will have tests of the speed and pressure of blood flow through their body: Blood pressure cuffs will be placed on each arm and leg; electrodes will be placed on the wrists and a microphone on the chest. The study has a 3-month lead-in period. Participants will not take the study drug during this time. They will continue with their usual medical care. They will have 2 phone calls with the study team. Baricitinib is a tablet taken by mouth. Participants will take 1 or 2 tablets by mouth every day for 6 months. They will start with a low dose and may increase to a higher dose. Blood and urine tests will be repeated during each study visit. Other tests may also be repeated during some visits. A skin sample may also be taken....

Detailed description

Study Description: This is an open-label, dose-titration, pilot trial to assess the safety of the Janus-associated kinase (JAK) inhibitor baricitinib in individuals with Job s syndrome with lupus-like features and/or atopic dermatitis (AD). Eligible participants will complete screening 3 months prior to the start of the trial and keep track of their infections and eczema to monitor Job s disease activity and ensure disease stability prior to initiation of baricitinib treatment. Those with stable disease will proceed to open-label treatment with baricitinib for 180 days. Primary Objective: To determine the safety and tolerability of JAK inhibitor treatment (baricitinib) in patients with Job s syndrome with lupus-like disease and/or AD. Secondary Objectives: 1. To assess changes in Candida and/or bacterial infections. 2. To evaluate the effect of baricitinib on lupus-like symptoms. 3. To evaluate the effect of baricitinib on AD. 4. To investigate the effect of baricitinib on quality of life (QOL). Exploratory Objectives: To investigate the effect of baricitinib on improving histologic and immunologic abnormalities in blood and affected organs and tissues. Primary Endpoints: 1\. Incidence of serious adverse events (SAEs), adverse events (AEs) requiring study drug discontinuation. Secondary Endpoints: 1. Incidence of Candida and/or bacterial infections. 2. Mean change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score from day -90 to day 0 and then from day 0 to days 90 and 180. 3. Mean change in Eczema Area and Severity Index (EASI) score from day -90 to day 0 and then from day 0 to days 90 and 180. 4. Mean change in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score from day -90 to day 0 and then from day 0 to days 90 and 180. 5. Mean change in the Physician Global Assessment (PGA) score from day -90 to day 0 and then from day 0 to days 90 and 180. 6. Mean change in the 36-Item Short Form Survey (SF-36) score (adults) from day -90 to day 0 and then from day 0 to days 90 and 180. 7. Mean change in the Patient Reported Outcomes Measurement Information System (PROMIS) score from day -90 to day 0 and then from day 0 to days 90 and 180. 8. Mean change in the Dermatology Life Quality Index (DLQI) score (adults) from day -90 to day 0 and then from day 0 to days 90 and 180. 9. Mean change in the Children s Dermatology Life Quality Index (CDLQI) score (pediatrics) from day -90 to day 0 and then from day 0 to days 90 and 180. 10. Mean change in the Pediatric Quality of Life Inventory (PedsQL) score (pediatrics) from day -90 to day 0 and then from day 0 to days 90 and 180. Exploratory Endpoints: 1. Changes in serum cytokines and chemokines between day -90 to day 0 and then day 0 to days 90 and 180. 2. Changes in neutrophil extracellular trap (NET) complexes between days -90 to day 0 and then from day 0 to days 90, and 180. 3. Changes in Transcriptional alterations and pathway analysis using scRNAseq on peripheral blood mononuclear cells (PBMCs) and neutrophils between days -90 to day 0 and then from day 0 to days 90, and 180. 4. Changes in skin biopsy - histopathology and anatomic pathology from day 0 to day 180. 5. Changes in immunophenotyping between days -90 to day 0 and then from day 0 to days 90, and 180. 6. Changes in phospho-signal transducer and activator of transcription (STAT) flow cytometry between days -90 to day 0 and then from day 0 to days 90, and 180. 7. Changes in arterial stiffness- assessment of vascular functions (assessed via cardio-ankle vascular index \[CAVI\]) between day -90 and day 0, and then between day 0 and days 90 and 180. 8. Changes in autoantibody levels from day -90 to day 0 and then from day 0 to days 90 and 180. 9. Changes in skin microbiome over the 180-day treatment period. 10. Changes in serum metabolomics from day -90 to day 0 and then from day 0 to days 90 and 180. 11. Changes in serum proteomics from day -90 to day 0 and then from day 0 to days 90 and 180.

Conditions

• Hyper IgE Syndrome From STAT3 Mutation
• Job s Syndrome
• HIES
• Lupus
• Atopic Dermatitis

Interventions

Type	Name	Description
DRUG	baricitinib	The planned duration of baricitinib treatment is 180 days. The treatment period will begin on Day 0 at dose level 1 (2 mg once daily) and will continue for 90 days. Following evaluation of safety, participants will be titrated to dose level 2 (4 mg once daily) provided the investigator determines it is safe and appropriate to do so. Study participants will continue on dose level 2 for 90 days.

Timeline

• Start date: 2026-04-22
• Primary completion: 2030-05-01
• Completion: 2030-10-01
• First posted: 2025-12-04
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study