Open Label Pilot Trial of Rituximab in Lupus Membranous Nephritis

May 13, 2015 updated by: Northwell Health

The objective of this study is to assess the as efficacy of rituximab as induction therapy in membranous lupus nephritis. Safety and tolerability will additionally be assessed. Subjects will receive open-label 2 courses of rituximab at baseline and at 6 months. They will be followed monthly for 18 months to assess response and durability of response.

The hypothesis: B cell depletion will be an effective safe and well tolerated treatment for membranous lupus nephritis (Class V).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age of a minimum of 18 years old
  • Able and willing to give written informed consent and comply with the requirements of the study protocol
  • Negative serum pregnancy test (for women of child bearing potential)
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
  • Diagnosis of SLE per current ACR classification criteria (at least 4 of 11 criteria)
  • Base line proteinuria >2g/24h
  • Kidney biopsy within 12 months of enrollment with membranous L.N. (ISN/RPS V)
  • Full dose ACE inhibition (or ARB) for a minimum of 8 weeks at day 0. Patients may be on less than full dose due to lack of tolerability
  • Stable < 0.5mg/kg corticosteroid dose in the 4 weeks prior to screening (including no corticosteroid)
  • Background immunosuppressives to include azathioprine, cyclosporine A, mycophenolate mofetil, methotrexate and/or an anti-malarial for > 6 months with stable dose(s) for 1 month prior to screening/enrollment will be allowed. Patients receiving cyclophosphamide and/or leflunomide will be excluded from this study.

Exclusion Criteria:

  • Treatment with cyclophosphamide within 3 months of screening
  • Use of high dose steroids (>0.5 mg/kg/ day) in the 4 weeks prior to screening
  • ANC < 1.5 x 103
  • Hemoglobin: < 8.0 gm/dL
  • Platelets: < 100,000/mm
  • AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
  • Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody)
  • History of positive HIV (HIV conducted during screening if applicable)
  • Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
  • Receipt of a live vaccine within 4 weeks prior to randomization
  • Previous Treatment with Rituximab (MabThera® / Rituxan®)
  • Previous treatment with Natalizumab (Tysabri®)
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • History of recurrent significant infection or history of recurrent bacterial infections
  • Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
  • Ongoing use of high dose steroids (>0.5 mg/kg/ day ) or unstable steroid dose in the past 4 weeks
  • Lack of peripheral venous access
  • History of drug, alcohol, or chemical abuse within 6 months prior to screening
  • Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
  • Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • History of psychiatric disorder that would interfere with normal participation in this protocol
  • Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Inability to comply with study and follow-up procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Rituximab
Subjects receive rituximab in an open label manner
Drug: Rituximab
375mg/m2 q week x 4; repeated in 6 months
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy at 6 months post treatment and durability of response at 12 months post treatment will be determined by: reduction in 24 hour urinary protein excretion, reciprocal creatinine, urinary sediment
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from baseline at 6 and 12 months in non-renal SLE disease activity (BILAG), lupus serologies (anti-dsDNA antibodies) and complement consumption (C3, C4), serum albumin, cholesterol, triglycerides
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwell Health

Investigators

  • Principal Investigator: Cynthia Aranow, MD, Feinstein Institute for Medical Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

May 22, 2009

First Submitted That Met QC Criteria

May 26, 2009

First Posted (ESTIMATE)

May 27, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

May 14, 2015

Last Update Submitted That Met QC Criteria

May 13, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U2971g

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lupus Nephritis

Clinical Trials on Rituximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe