Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy

• Register: ClinicalTrials.gov
• Last refreshed on: 29 April 2024
• Main ID: NCT00977977
• Date of registration: 15/09/2009
• Prospective Registration: Yes
• Primary sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Public title: Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
• Scientific title: Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
• Date of first enrolment: December 22, 2010
• Target sample size: 30
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT00977977
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Meryl A Waldman, M.D.
• Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

• Name: Meryl A Waldman, M.D.

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the
following criteria:

1. Stated willingness to comply with all study procedures and availability for the
duration of the study

2. Male or female, >= 18 years of age

3. Nephrotic range proteinuria that persists for at least 6 months post diagnosis of
membranous nephropathy greater than 3.5 grams /24 hours (based on 24-hour urine
collection).

a. If the subject s renal function rapidly declines in less than 6 months could
proceed with immunosuppression therapy sooner such as complications of the nephrotic
syndrome that are not controlled with supportive therapy or evidence of decline in
glomerular filtration rate or proteinuria >8 grams/day. Subjects with declining renal
function and/or high-grade proteinuria due to MN are considered "high risk" subjects
and have a higher probability of progression to end stage kidney disease.

4. Nephrotic range proteinuria (>3.5 g/24 hours) that persists despite angiotensin
antagonist therapy (ACE inhibitor or ARB) for at least 2 months unless intolerant.

a. The rationale is that blockade of the renin angiotensin system (RAAS) is widely
considered to be part of the standard of care treatment for subjects with the
nephrotic syndrome. Nephrotic range proteinuria will be defined as an estimated
average proteinuria >3.5 g/24 hours in adults based on at least two 24-hour urine
protein excretions obtained prior to initiating therapy. Incomplete urine

collections (based on inadequate creatinine excretion) will be excluded.

5. Renal biopsy within the past 24 months must reveal typical changes of membranous
nephropathy by light and electron microscopy or a positive anti-PLA2R antibody test in
the serum. There has been a change in the management strategies for MN such that a
renal biopsy is not absolutely required for diagnosis if patient has positive
circulating anti-PLA2R antibody.

a. Based on published KDIGO 2021 Clinical Practice Guidelines 3.1.1 patients with MN
who are positive for anti-PLA2R do not require renal biopsy as long as renal function
is normal (eGFR >60) and has not had immunosuppression as it has been demonstrated
that results of the biopsy have not altered clinical approach and management. If not
PLA2R positive, renal biopsy within 24 months is still required.

6. Blood pressure <=140/90 on >75% of measurement while on anti-hypertensive treatment
for at least 1-2 months.

7. There is no evidence to suggest secondary forms of membranous nephropathy.

8. Ability to take oral medication and be willing to adhere to the cyclosporine regimen

9. For females of reproductive potential: use of highly effective contraception for at
least 1 month prior to screening and agreement to use such a method during study
participation and for 12 months after the last Rituximab infusion.

10. For males of reproductive potential: use of condoms or other methods to ensure
effective contraception with partner.

11. Ability of subject to understand and the willingness to sign a written informed
consent document.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation
in this study:

1. Estimated GFR<40 ml/min/1.73 m^2 from the preceding 2 months prior to enrollment while
on ACEI/ARB therapy.

2. Immunosuppressive medications or experimental medications of any type during the
three-month period prior to initiating Rituximab and cyclosporine.

3. Prior exposure to cyclosporine or tacrolimus for more than 6 months and/or evidence of
intolerance or toxicity associated with cyclosporine treatment of any duration
including irreversible azotemia, liver dysfunction or hypertension

4. Rituximab use within the previous 12 months.

5. Clinically significant medical conditions (i.e., severe heart failure NYHA class IV,
uncontrolled coronary artery disease/unstable angina), which in the opinion of the
investigator, could increase the subject s risk of participating in the study or could
confound the interpretation of the results of the study.

6. Positive HIV serology

7. Positive HCV serology

8. Active acute or chronic infection requiring antimicrobial therapy or serious viral
infection cytomegalovirus, herpes simplex, varicella zoster virus (chicken pox or
shingles), Parvovirus B19 (can be based on previous medical records within the past
24-months)

9. Live viral vaccines within one month prior to Rituximab.

10. Pregnancy or lactation

11. Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal
cell carcinoma of the skin. The rationale is that immunosuppression may accelerate
cancer progression.

12. Clinical evidence of cirrhosis or chronic active liver disease sufficiently severe to
impair cyclosporine metabolism; this would include a prolonged prothrombin time.

13. Cytopenia (neutrophils <1500/mm^3 and/or thrombocytopenia <75,000) and/or CD4 T cell
count <200/mm^3). The rationale is that Rituximab therapy may be followed by cytopenia
with the granulocyte lineage being at greatest risk. Patients with low CD4 T cell
counts are prone to infection which can be exacerbated by Rituximab.

14. Diabetes mellitus. The rationale is that diabetes may lead to worsening of proteinuria
that would not respond to immunosuppression and would confound the results.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Autoimmune Disease

Nephrotic Syndrome

Glomerular Disease

Membranous Glomerulonephritis

Proteinuria

Intervention(s)

Drug: Oral Cyclosporine

Drug: Rituximab Infusion

Primary Outcome(s)

Percentage of complete and partial remissions (CR and PR) [Time Frame: 24 months]

Percentage of complete and partial remissions (CR and PR) [Time Frame: 12 months]

Percentage of complete and partial remissions (CR and PR) [Time Frame: 6 months]

Percentage of complete and partial remissions (CR and PR) [Time Frame: 18 months]

Safety [Time Frame: 24 months]

Secondary Outcome(s)

Time to relapse (in those who achieved a remission) [Time Frame: Baseline to 24 months]

Time to remission Baseline to 24 months [Time Frame: Baseline to 24 months]

Change in proteinuria from baseline to 12 months [Time Frame: Baseline to 12 months]

Secondary ID(s)

09-DK-0223

090223

Source(s) of Monetary Support

Please refer to primary and secondary sponsors