Efficacy, Safety and Immunological Evaluation of Upadacitinib for Relapsing Polychondritis

Relapsing polychondritis (RP) is a rare, systemic autoimmune disorder characterized by episodic inflammation of cartilaginous structures.

The goal of this clinical trial is to learn if drug Upadacitinib works to treat relapsing polychondritis in adults. It will also learn about the safety of drug Upadacitinib. The main questions it aims to answer are:

• Does drug Upadacitinib reduce the disease activity of relapsing polychondritis?
• What medical problems do participants have when taking drug Upadacitinib? Researchers will compare drug Upadacitinib to conventional therapies (treatment with corticosteroids combined with immunosuppressants) to see if drug Upadacitinib works to treat relapsing polychondritis.

Participants will:

• Take drug Upadacitinib or corticosteroids combined with immunosuppressants every day for 24 weeks.
• Visit the hospital once every month for checkups and tests. This clinical study will explore the efficacy and immunological evaluation of Upadacitinib in the treatment of RP.

Study Overview

• Status: Recruiting
• Conditions: Relapsing Polychondritis
• Intervention / Treatment: Drug: Upadacitinib; Drug: corticosteroids and immunosuppressants

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jing He; Phone Number: +8618611707347; Email: hejing1105@126.com
• Study Contact Backup: Name: Yifan Wu; Phone Number: +8618766399762; Email: 2411210283@stu.pku.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Department of Rheumatology and Immunology, Peking University People's Hospital
      • Contact: Jing He, MD and PhD; Phone Number: +8618611707347; Email: hejing1105@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Male or female ≥18 and ≤70 years
• 2.Meet the revised Michet criteria
• 3.Patients had an inadequate response to standard treatment for ≥ 4 weeks. The background treatment included corticosteroids (≤0.5 mg/ kg), immunosuppressants ( methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil leflunomide, or cyclophosphamide)
• 4. Negative urine pregnancy test
• 5. Written informed consent form

Exclusion Criteria:

Any subject who meets any of the following criteria shall be excluded:

• 1.Use rituximab or other monoclonal antibodies within 2 months.
• 2.1 months after treatment with high dose glucocorticoid (> 1 mg/kg/d).
• 3.Serious complications: heart failure (≥ New York Heart Association（NYHA） III grade), renal insufficiency (creatinine clearance rate ≤ 30 ml/min), liver function insufficiency (serum alanine transaminase or glutamic-pyruvic transaminaseT > 3 times normal upper limit, or total bilirubin > normal upper limit)
• 4.Other serious, progressive or uncontrollable hematological, gastrointestinal, endocrine, lung, heart, nerve, or brain diseases (including demyelination diseases, such as multiple sclerosis).
• 5.Known allergies, hyperresponsiveness or IL-2 or its excipients are intolerant.
• 6.Severe infections (including, but not limited to, hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus, tuberculosis infection), hospitalization for infection, or intravenous antibiotics 2 months before the first dose of treatment.
• 7.Chest imaging showed abnormalities in malignant tumors or current active infections (including tuberculosis) within 3 months before the first use of the study.
• 8.Infected with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, consult a doctor with expertise in the treatment of HIV or hepatitis C virus infection.
• 9.There has been any known malignant tumor or history of malignant tumor in the past 5 years (with the exception of non-melanoma skin cancer, non-melanoma skin cancer with no sign of recurrence or surgically cured cervical tumor within 3 months of use of the first study preparation).
• 10.There are uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past three years, which may hinder the successful completion of the study. 11.Within 3 months before the first injection of the research agent, during the study period or within 4 months after the last injection of the research agent, any live virus or bacterial vaccine is received or expected to be received. Bacillus Calmette-Guerin was vaccinated within 12 months after screening.
• 11.Pregnant and lactating women (WCBP) are reluctant to use medically approved contraceptives during and 12 months after treatment.
• 12.Men whose partners have fertility potential but do not want to use appropriate medically approved contraceptives during and within 12 months of treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group	Drug: Upadacitinib; Upadacitinib is an oral Janus kinase (JAK) inhibitor used in this study to treat patients with relapsing polychondritis. The drug is administered at a dose of 15 mg once daily for a duration of 24 weeks.
Active Comparator: Countrol Group	Drug: corticosteroids and immunosuppressants; Corticosteroids combined with immunosuppressants is a conventional treatment for relapsing polychondritis. In this study, it serves as the control arm against Upadacitinib for the treatment of relapsing polychondritis. Dosing is tailored to the individual patient's condition, with the selection of different types of corticosteroids and immunosuppressive agents based on the specific needs of the patient's clinical profile.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRP variation	Modification of inflammatory makers	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapsing Polychondritis Disease Activity Index		24 weeks
Variation of lymphocyte subpopulations and cytokine during the treatment of upadacitinib	Cytokine and lymphocyte subgroups of T cell, B cell and NK cell are analyzed during the treatment.	24 weeks
Improvement of clinical symptom measured by 5-level EQ-5D version (EQ-5D-5L)	The EQ-5D-5L is a health-related quality-of-life instrument developed by the EuroQol Group. It is designed to measure health status across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems.	24 weeks
Alteration of inflammatory biomarkers and pathways after treatment of upadacitinib	We will investigate the potential pathways through which Upadacitinib exerts its effects and examine the changes in inflammatory biomarkers during the experimental process	24 weeks
Incidence of Treatment-Emergent Adverse Events	Adverse events includes influenza-like symptoms, infection, fever, tumor,drug-induced liver and kidney damage.	24 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Zhanguo Li, Peking University Institute of Rheuamotology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Upadacitinib; Relapsing polychondritis
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Connective Tissue Diseases; Cartilage Diseases; Polychondritis, Relapsing; Janus Kinase Inhibitors; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Upadacitinib; Immunosuppressive Agents
• Other Study ID Numbers: Upadacitinib RP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes