Randomized Trial Comparing Rituximab Against Mycophenolate Mofetil in Children Wtih Refractory Nephrotic Syndrome

NCT02390362 | Terminated Phase 3 Results DMC

• 1 other identifier: RAMP001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

We hypothesize that the anti-CD20 monoclonal antibody Rituximab will be more effective than MMF in maintaining remission in children with frequent relapsing or steroid dependent nephrotic syndrome who have had one relapse while receiving MMF. We will conduct a randomized study comparing two Rituximab infusions and continued MMF treatment. We plan to enroll 64 to have a comparater group of 58 (29 in each arm).

Conditions

Frequent Relapsing Nephrotic Syndrome; Steroid Dependent Nephrotic Syndrome

Outcome Measures

Primary Outcomes (1)

• Relapse Free Survival

  6 months

Secondary Outcomes (1)

• Relapse Free at 12 Months

  12 months

Study Arms (2)

Rituximab

EXPERIMENTAL

Rituximab 375 mg/m2 will be administered intravenously on Study weeks 1 \& 3.

Drug: Rituximab

Mycophenolate Mofetil (MMF)

ACTIVE COMPARATOR

Mycophenolate Mofetil will be continued in the patients in the MMF arm at a standard oral dose of 600 mg/m2 PO, BID starting on Study week 1 and continuing for 12 months

Drug: MMF

Interventions

Rituximab DRUG

We hypothesize that the anti-CD20 monoclonal antibody Rituximab will be more effective in maintaining remission in children who have already had one relapse while receiving MMF

Rituximab

MMF DRUG

Subjects randomized to MMF, will continue MMF as scheduled by the investigator

Mycophenolate Mofetil (MMF)

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• SDNS or FRNS
• Complete remission, defined by absence of edema and 3 consecutive daily urine dipstick readings of trace or negative for protein
• Must be taking MMF and have had at least one relapse while taking MMF in the prior 6 months that responded to corticosteroid treatment by re-entering complete remission at least 2 weeks prior to study entry.
• BMI prior to onset of NS \<99th percentile
• Age 1-18 years
• Estimated GFR \>40 ml/min/1.73m² (by Modified Schwartz formula)
• Negative serum pregnancy test (for females who are tanner stage 4 or 5)
• Males and females of reproductive potential (sexually active in boys or post-menarche in girls) must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment

You may not qualify if:

• Prior therapy with rituximab, tacrolimus or cyclosporine
• Prior therapy with cytotoxic agents in the past 90 days
• History of genetic defects known to directly cause nephrotic syndrome (i.e. NPHS2 (podocin), NPHS1 (nephrin), PLCE1, WT1)
• History of or concomitant severe, active infection (e.g. HIV, hepatitis B, hepatitis C)
• History of diabetes mellitus
• History of organ or bone marrow transplant
• Secondary nephrotic syndrome (i.e. reflux nephropathy, IgA nephropathy, lupus nephritis, etc)
• Live viral vaccines administered in the past 6 weeks (42 days)
• Participation in another therapeutic trial within 30 days of enrollment
• Allergy to study medications
• ANC \< 1.5 x 103
• Hemoglobin: \< 8.0 gm/dL
• Platelets: \< 100,000/mm
• AST or ALT \>2.5 x Upper Limit of Normal at the local institutions laboratory
• Positive Hepatitis B or C serology (Hep B Surface antigen, Hep B Core antibody, and Hep C antibody)

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• Emory University: collaborator
• Children's Healthcare of Atlanta: collaborator
• Genentech, Inc.: collaborator
• The NephCure Foundation: collaborator

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (1)

• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.

  PMID: 39513526 DERIVED

MeSH Terms

Conditions

Nephrotic Syndrome

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study terminated early, sponsor pulled funding associated with enrollment milestones. At the time of termination, 2 subjects were active in the study. 1 was randomized to study drug, the other to the comparator drug. Not enough data for analysis.

Results Point of Contact

• Title: William E. Smoyer, MD.
• Organization: The Research Institute at Nationwide Children's Hospital

william.smoyer@nationwidechildrens.org

6147222683

Study Officials

• William Smoyer, MD

  The Research Institute at Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

• Laurence Greenbaum, MD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: William E. Smoyer, MD

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: January 1, 2015
• Primary Completion: December 7, 2016
• Study Completion: January 18, 2017
• Last Updated: March 26, 2019
• Results First Posted: March 26, 2019

Record last verified: 2019-03

Locations

US (1)