Bortezomib for the Treatment of Refractory Rheumatoid Arthritis

An Exploratory Clinical Study on Bortezomib for the Treatment of Refractory Rheumatoid Arthritis

This is a single-center, single-arm, prospective study on the efficacy and safety of Bortezomib in addition to standard therapy in patients with refractory rheumatoid arthritis.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: bortezomib

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qian Wang, MD; Phone Number: 86-13681211155; Email: zhengaqian@sina.com
• Study Contact Backup: Name: Xinping Tian, MD; Phone Number: 86-13691165939; Email: tianxp6@126.com

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Qian Wang, MD; Phone Number: 86-13681211155; Email: zhengaqian@sina.com
    • Contact: Xinping Tian, MD; Phone Number: 86-13691165939; Email: tianxp6@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18~70 years.
2. Fulfilling the 2010 ACR/EULAR classification criteria for RA.
3. Failed to at least two bDMARDs (including but not limited to TNF inhibitors, IL-6 receptor inhibitors, T cell costimulation inhibitor and anti-B cell biologics) or tsDMARDs (including but not limited to JAK inhibitors) in combination with a csDMARD for at least 12 weeks. The dosage of cs/b/tsDMARDs needs to be stable for at least 6 weeks.
4. For patients receiving glucocorticoids, the dosage of GC needs to be less than or equal to 10mg prednisone equivalent and stable for at least 6 weeks.
5. For patients receiving non-steroid anti-inflammatory drugs, the dosage of NSAID needs to be stable for at least 2 weeks.
6. Neutrophil≥1.0×10^9/L, platelet≥100×10^9/L, alanine transaminase (ALT) and aspartate aminotransferase (AST) within 3 ULN, total bilirubin within 1.5 ULN.
7. Informed consent obtained.

Exclusion Criteria:

1. Other concomitant autoimmune diseases (except for Sjogren's syndrome secondary to rheumatoid arthritis).
2. The presence of severe uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neuropsychiatric disorders, or abnormal laboratory tests. The investigators consider that participation in the study may make unacceptable risks to the subjects.
3. A history of malignancy with a clinical cure time of less than 5 years.
4. Pregnant or breast-feeding women, or planning to get pregnant or start breastfeeding during the study.
5. Vaccinated with live attenuated virus within 4 weeks before entering the study.
6. Allergic to bortezomib or mannitol.
7. Participated in any other investigational drug trial within 12 weeks before study initiation.
8. Active hepatitis or liver disease at the time of screening: Hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibodies (HCVAb) positive; (Note: If Hepatitis B Core Antibody, (HBcAb) is positive and HBsAg is negative, HBV-DNA detection will be performed, patient is eligible if HBV-DNA was negative).
9. Active herpes zoster infection, or severe infection requiring intravenous antibiotics or hospitalization occurred 12 weeks before study initiation.
10. Other conditions that not suitable for inclusion in the study, assessed by the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: bortezomib; bortezomib added on previous treatment	Drug: bortezomib; bortezomib 2mg/week subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAS28 remission or LDA at week 24	Proportion of patients who achieve remission or low disease activity (LDA) at week 24 according to DAS 28.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAS28 improvement at week 12	Proportion of patients who achieve remission or low disease activity at week 12 according to DAS 28. Proportion of patients who achieve at least a 50% reduction of DAS28 at week 12.	12 weeks
SDAI improvement at week 12 and remission or LDA at week 24	Proportions of patients who achieve remission or low disease activity at week 12 and week 24 according to SDAI. Proportion of patients who achieve at least a 50% reduction of SDAI at week 12.	24 weeks
CDAI improvement at week 12 and remission or LDA at week 24	Proportions of patients who achieve remission or low disease activity at week 12 and week 24 according to CDAI. Proportion of patients who achieve at least a 50% reduction of CDAI at week 12.	24 weeks
ACR20, ACR50 and ACR70 at week 12 and week 24	Proportions of patients who achieve ACR20, ACR50 and ACR70 at week 12 and week 24.	24 weeks
Changes in glucocorticoid dose	Changes in glucocorticoid dose at week 12 and 24 from baseline.	24 weeks
Adverse events during the study	All adverse events, severe adverse events and proportion of patients who discontinued bortezomib due to adverse events from the first dose of bortezomib to 4 weeks after the last dose.	28 weeks

Collaborators and Investigators

• Sponsor: Chinese SLE Treatment And Research Group
• Investigators: Principal Investigator: Xinping Tian, MD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: April 6, 2023
• First Posted (Actual): April 10, 2023

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; bortezomib
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: Bortezomib-RA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No