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

NCT07262983 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002176002176-I
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

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

Keywords

Hyper IgE Syndrome From STAT3 Mutation; Job s syndrome; HIES; Lupus; Atopic Dermatitis; Lupus-like Disease; JAK Inhibition; Janus Kinases

Outcome Measures

Primary Outcomes (1)

• Incidence of SAEs, AEs requiring study drug discontinuation.

  To determine the safety and tolerability of JAK inhibitor treatment (baricitinib) in patients with Job s syndrome with lupus-like disease and/or AD.

  Through end of study

Secondary Outcomes (10)

• Incidence of Candida and/or bacterial infections.

  Through end of study

• Mean change in CLASI score from day -90 to day 0 and then from day 0 to days 90 and 180.

  From day -90 to day 0 and then from day 0 to days 90 and 180

• Mean change in EASI score from day -90 to day 0 and then from day 0 to days 90 and 180.

  From day -90 to day 0 and then from day 0 to days 90 and 180

• Mean change in SLEDAI score from day -90 to day 0 and then from day 0 to days 90 and 180.

  From day -90 to day 0 and then from day 0 to days 90 and 180

• Mean change in the PGA score from day -90 to day 0 and then from day 0 to days 90 and 180.

  From day -90 to day 0 and then from day 0 to days 90 and 180

Study Arms (1)

Interventional

EXPERIMENTAL

baricitinib

Drug: baricitinib

Interventions

baricitinib DRUG

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.

Interventional

Eligibility Criteria

• Age: 12 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Must be able to understand and provide informed consent or assent.
• Aged \>=12 years.
• Documented STAT3 variant causing hyper-IgE syndrome.
• Enrollment in NIH protocol 00-I-0159, Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES).
• a. Presence of SLE and/or AD as follows: SLE patients should meet either Systemic Lupus International Collaborating Clinics (SLICC) or 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) SLE classification criteria. AD is defined as EASI tool score \>=16 and body surface area tool score of 10% at screening.
• Ability to take oral medication and be willing to adhere to the study intervention regimen.
• For individuals on glucocorticoids, the dose must be less than 10 mg daily and stable for the 30 days prior to Day 0.
• For individuals on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, the dose must have been stable for 90 days prior to Day 0. The maximum allowed dose is hydroxychloroquine 400 mg/day or 6.5 mg/kg/day, whichever is greater. The maximum allowed dose for chloroquine phosphate is 500 mg daily, and for quinacrine is 100 mg daily.
• Individuals may be on lipid-lowering medications if initiated at least 90 days prior to Day 0, and the dose must be stable for 30 days prior to Day 0.
• Individuals of reproductive potential must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy while on study drug. Acceptable methods of contraception include:
• Intrauterine device (IUD)
• Bilateral tubal ligation
• Abstinence
• Vasectomized partner

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Known history of hypersensitivity to baricitinib or other JAK inhibitors.
• Current or recent use of any investigational drug/intervention (within 6 months or 5 half-lives, whichever is longer, prior to Day 0) except for COVID-19 vaccines or therapies that have been granted an FDA emergency authorization.
• Scheduled to participate in another clinical study involving an investigational drug during the course of this study.
• Use of systemic immunosuppressive or immune-modulating agents within 90 days prior to Day 0, except systemic steroids \<=10 mg of prednisone equivalent per day.
• Current or prior treatment with rituximab in the 6 months prior to Day 0.
• Current treatment with methotrexate, mycophenolate mofetil, other less common immunomodulatory drugs such as those falling into the class of disease-modifying antirheumatic drugs (DMARDs), belimumab, and other immunosuppressive biologics not otherwise specified herein. Participants previously on methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or belimumab, other immunosuppressive biologics, or DMARDs should have been withdrawn from the drug for at least 90 days prior to Day 0.
• Treatment with cyclophosphamide and pulse methylprednisolone within 6 months prior to Day 0.
• Hypercholesterolemia: Values after 8- to 12-hour fasting blood specimen: total cholesterol \>250 mg/dL or LDL \>180 mg/dL or hypertriglyceridemia (triglyceride \>300 mg/dL) within 90 days prior to Day 0.
• History of alcohol or drug abuse within 6 months prior to Day 0.
• Presence of 1 or more of the following clinically significant laboratory abnormalities:
• Serum ALT \>=3 times ULN.
• Serum total bilirubin \>=2 times ULN.
• ANC \<=750 cells/microL.
• Hemoglobin \<=9.0 g/dL.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Goel RR, Nakabo S, Dizon BLP, Urban A, Waldman M, Howard L, Darnell D, Buhaya M, Carmona-Rivera C, Hasni S, Kaplan MJ, Freeman AF, Gupta S. Lupus-like autoimmunity and increased interferon response in patients with STAT3-deficient hyper-IgE syndrome. J Allergy Clin Immunol. 2021 Feb;147(2):746-749.e9. doi: 10.1016/j.jaci.2020.07.024. Epub 2020 Aug 5.

  PMID: 32768442 BACKGROUND

• Lobo PB, Guisado-Hernandez P, Villaoslada I, de Felipe B, Carreras C, Rodriguez H, Carazo-Gallego B, Mendez-Echevarria A, Lucena JM, Aljaro PO, Castro MJ, Noguera-Ucles JF, Milner JD, McCann K, Zimmerman O, Freeman AF, Lionakis MS, Holland SM, Neth O, Olbrich P. Ex vivo effect of JAK inhibition on JAK-STAT1 pathway hyperactivation in patients with dominant-negative STAT3 mutations. J Clin Immunol. 2022 Aug;42(6):1193-1204. doi: 10.1007/s10875-022-01273-x. Epub 2022 May 4.

  PMID: 35507130 BACKGROUND

• Hasni SA, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Carlucci PM, Wang X, Naqi M, Playford MP, Goel RR, Li X, Biehl AJ, Ochoa-Navas I, Manna Z, Shi Y, Thomas D, Chen J, Biancotto A, Apps R, Cheung F, Kotliarov Y, Babyak AL, Zhou H, Shi R, Stagliano K, Tsai WL, Vian L, Gazaniga N, Giudice V, Lu S, Brooks SR, MacKay M, Gregersen P, Mehta NN, Remaley AT, Diamond B, O'Shea JJ, Gadina M, Kaplan MJ. Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus. Nat Commun. 2021 Jun 7;12(1):3391. doi: 10.1038/s41467-021-23361-z.

  PMID: 34099646 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Alexandra F Freeman, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexandra F Freeman, M.D.

CONTACT

(301) 594-9045; sarthak.gupta@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: December 4, 2025
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: April 16, 2026

Record last verified: 2025-11-25

Locations

US (1)