A Randomized, Controlled Clinical Study of Rituximab in Treatment of Primary IgA Nephropathy

NCT05824390 | Unknown Phase 4

• 1 other identifier: RuijinHRIGA
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

A study to evaluate safety and activity in treatment of IgAN patients using Rituximab in combination with RASi(ACEI and/or ARB) compared with RASi.

Conditions

IgA Nephropathy

Outcome Measures

Primary Outcomes (1)

• Changes in proteinuria levels over 1 year compared with baseline

  changes in proteinuria levels over 1 year compared with baseline

  1 year

Secondary Outcomes (9)

• The proportion of 50% reduction in mean urinary protein compared with baseline over 1 year

  1 year

• The proportion of 50% reduction in mean urinary protein compared with baseline over 6 months

  6 months

• Changes in proteinuria levels over 6 months compared with baseline

  6 months

• Changes in eGFR levels over 1 year compared with baseline

  1 year

• Changes of Gd-IgA1 levels

  1 year

Study Arms (2)

Group A ( ACEi and / or ARB + rituximab group )

EXPERIMENTAL

Patients in the experimental group were treated with the maximum tolerable dose of angiotensin converting enzyme inhibitor ( ACEI ) and / or angiotensin II receptor blocker ( ARB ) combined with rituximab. The specific usage and dosage are as follows : On the basis of the use of ACEI and / or ARB, rituximab was used on D1 and D31 days, 1 g each time, intravenous drip, twice in total. Add 1 g rituximab at 6 months. All patients who received rituximab were given oral acetaminophen ( 1g ), diphenhydramine hydrochloride ( 50mg ) and intravenous methylprednisolone ( 40mg ) 30-60min before the beginning of infusion. ACEI and / or ARB were given daily maximum tolerable dose according to individual factors of subjects.

Drug: rituximab group

Group B ( ACEi and / or ARB )

NO INTERVENTION

According to the individual factors of the subjects, the maximum tolerable dose of angiotensin converting enzyme inhibitor ( ACEI ) and / or angiotensin II receptor blocker ( ARB ) were used daily.

Interventions

rituximab group DRUG

Rituximab is a human-mouse chimeric monoclonal antibody specifically targeting B cell surface antigen CD20. CD20 may act as a calcium channel to play a certain signal role and participate in the regulation of B cell maturation and differentiation. Once combined with CD20, RTX consumed CD20 + B fines through antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and direct induction of apoptosis. Recent studies have shown that B cell depletion therapy has a certain effect on many autoantibodies-mediated kidney diseases ( such as membranous nephropathy, lupus nephritis, etc. ). Therefore, rituximab combined with CD20 antigen on the surface of B cells can exhaust B cells that produce antibodies and play a therapeutic role by reducing antibody production, so this therapy also has potential therapeutic value for IgAN patients.

Also known as: ACEi and / or ARB

Group A ( ACEi and / or ARB + rituximab group )

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years old, no gender limit;
• Renal biopsy confirmed primary IgA nephropathy;
• Assess glomerular filtration rate ( eGFR )\>30ml/min/1.73m2 (calculated according to the CKD-EPI formula);
• After 3 months of treatment with the maximum tolerated dose of ACEI and/or ARB, the following two points should be met:
• \) 24hurinary protein ≥ 1g; 2) Blood pressure \<130/80 mmHg; 5. Serum albumin\> 25g/L; 6. Voluntarily sign the informed consent.
• Note : It is suggested that active IgAN patients should be selected. Active IgAN is specifically defined as conforming to any of the following :
• ) intradermal augmentation ( E1 ),
• ) crescentic body 0 - 50 % ( C1 / C2 ),
• ) fibrinoid necrosis,
• ) more interstitial inflammatory cell infiltration. At the same time, the proportion of sclerosis was low ( spherical or segmental sclerosis ball \< 50 % ), and interstitial fibrosis was low ( below T2 ).

You may not qualify if:

• Glucocorticoid used for immunosuppressive therapy indications, such as : nephrotic syndrome, pathology for small lesions with IgA nephropathy. or the proportion of crescents confirmed by renal biopsy within 12 months was more than 50 %.
• Clinically confirmed cirrhosis, chronic active liver disease or hepatitis B, hepatitis C or HIV can detect viral replication.
• Clinically confirmed IgA nephropathy secondary to systemic diseases such as systemic lupus erythematosus, allergic purpura.
• Patients with non-simple IgA nephropathy, such as diabetic nephropathy or obesity-related nephropathy.
• A history of active systemic infection or severe infection occurred one month before enrollment.
• Those who are pregnant or lactating or unwilling to take contraceptive measures.
• Current or recent ( within 30 days ) exposure to any research drug. 8. Patients with allergic reactions to rituximab and / or known allergic reactions.
• Patients with allergic reactions to rituximab and / or known allergic reactions.
• Laboratory tests should be excluded if they meet the following standards :
• (1) Hemoglobin \<80g/L; (2) Platelets\<80×109/L; (3) Neutrophils \<1.0×109/L; (4) In addition to being related to the primary disease, aspartate aminotransferase (AST) or alanine aminotransferase (ALT)\>2.5×upper limit of normal; 10. Continuous use of hormones or other immunosuppressive therapy in the past 6 months; 11. Accompanying or past malignant tumors, except for fully treated skin basal or squamous cell carcinoma or cervical carcinoma in situ; 12. History of psychosis may interfere with normal participation in this study; 13. Patients with major heart or lung diseases (including obstructive pulmonary disease); 14. In acute and chronic tuberculosis infection period (tuberculin test positive, chest X-ray suspected tuberculosis patients); 15. Patients with history of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 16. Low weight (weight \< 50kg) should be excluded; 17. Other investigators judged patients unsuitable for the study.

Sponsors & Collaborators

• XIEJINGYUAN: lead
• Dongfang Hospital Affiliated to Tongji University: collaborator
• Shanghai Pudong New Area People's Hospital: collaborator
• Ruijin Hospital North Shanghai Jiao Tong University School of Medicine: collaborator
• Ningbo Municipal Yinzhou District No.2 Hospital: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Xiamen Humanity Hospital: collaborator
• Sir Run Run Shaw Hospital: collaborator

Study Sites (1)

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200001, China

Location

MeSH Terms

Conditions

Glomerulonephritis, IGA

Interventions

Angiotensin-Converting Enzyme Inhibitors

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Single (Participant)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: April 9, 2023
• First Posted: April 21, 2023
• Study Start: June 20, 2020
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: April 21, 2023

Record last verified: 2023-04

Locations

CN (1)