Frequent Relapsing Nephrotic SyndromePhase 3RAMPNCT02390362
Randomized Trial Comparing Rituximab Against Mycophenolate Mofetil in Children Wtih Refractory Nephrotic Syndrome
A Phase 3 study testing Rituximab and MMF in people with Frequent Relapsing Nephrotic Syndrome and Steroid Dependent Nephrotic Syndrome, run by Nationwide Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Frequent Relapsing Nephrotic Syndrome, Steroid Dependent Nephrotic Syndrome
- What is being tested?
- Rituximab and MMF
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to 18 Jan 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- • 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
Show all 34Show fewer
- 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)
- History of HIV infection
- 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 Natalizumab (Tysabri®)
- Previous Treatment with Rituximab (Rituxan®)
- Known hypersensitivity to Rituximab, to any of its excipients, or to murine proteins
- 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
- Lack of peripheral venous access
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Pregnant, lactating, or refusal of birth control in an adolescent of child-bearing potential
- Concomitant malignancies or previous malignancies
- 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
- Patients who fail screening due to an abnormal laboratory parameter may be rescreened within the next 6 months if the local PI believes that the abnormality was transient and not related to a chronic underlying disease. Rescreening may only occur once and may not occur within 2 weeks of the initial screen failure.
- If a patient has a clinically significant laboratory abnormality, the PI will be asked to define a follow-up plan (timing of repeating the laboratory test and/or additional work-up).
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
Official title: Randomized Trial Comparing Rituximab Against Mycophenolate Mofetil in Children Wtih Refractory Nephrotic Syndrome (RAMP)
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).
Read the detailed description
After screening, and eligibility criteria have been met, children with steroid dependent and frequent relapsing nephrotic syndrome (SDNS and FRNS) will be enrolled into a 53 week study. The study is comprised of 3 sections; screening, treatment, and followup.
Screening will be <4 weeks from Day 1/week 1. Treatment is Day 1/Week 1 and Day 15/Week 3. Follow-Up is Week 7, Week 13, Week 19, Week 27 and Week 53. Participants will be randomized by the study pharmacy between screening and treatment Day1. If participant is randomized to Rituximab, then Treatment Day 15 will be based on tolerance of Rituximab infusion.
Safety assessments will occur at every visit beginning with Day 1.
- Being tested
- Rituximab, MMF
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
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
MMFDrug
Subjects randomized to MMF, will continue MMF as scheduled by the investigator
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Rituximab 375 mg/m2 will be administered intravenously on Study weeks 1 \& 3. Receives: 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 Receives: Drug: MMF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse Free Survival
Measured: 6 months
Secondary outcomes (1)
Relapse Free at 12 Months
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study startJan 2015
- Primary completion7 Dec 2016
- Study completion18 Jan 2017
Why it stopped: Funding associated with enrollment milestones was withdrawn by Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Frequent Relapsing Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Emory University, Children's Healthcare of Atlanta, Genentech, Inc., The NephCure Foundation
- Responsible party
- Principal investigator, William Smoyer, Nationwide Children's Hospital
- Investigators
- William Smoyer, MD, Principal investigator, Nationwide Children's HospitalLaurence Greenbaum, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02390362
- Sponsor's protocol ID
- RAMP001
- Acronym
- RAMP
- Status last verified
- Mar 2019
- First submitted
- 11 Mar 2015
- Last updated
- 26 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 39513526
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial Comparing Rituximab Against Mycophenolate Mofetil in Children Wtih Refractory Nephrotic Syndrome (RAMP)
- ClinicalTrials.gov ID
- NCT02390362
- Acronym / sponsor ID
- RAMP / RAMP001
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding associated with enrollment milestones was withdrawn by Sponsor.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- Emory University, Children's Healthcare of Atlanta, Genentech, Inc., The NephCure Foundation
- Study start
- Jan 2015
- Primary completion
- 7 Dec 2016 (actual)
- Study completion
- 18 Jan 2017 (actual)
- First posted
- 17 Mar 2015 (estimated)
- Results
- Posted 26 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
After screening, and eligibility criteria have been met, children with steroid dependent and frequent relapsing nephrotic syndrome (SDNS and FRNS) will be enrolled into a 53 week study. The study is comprised of 3 sections; screening, treatment, and followup.
Screening will be <4 weeks from Day 1/week 1. Treatment is Day 1/Week 1 and Day 15/Week 3. Follow-Up is Week 7, Week 13, Week 19, Week 27 and Week 53. Participants will be randomized by the study pharmacy between screening and treatment Day1. If participant is randomized to Rituximab, then Treatment Day 15 will be based on tolerance of Rituximab infusion.
Safety assessments will occur at every visit beginning with Day 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab 375 mg/m2 will be administered intravenously on Study weeks 1 \& 3. |
| Mycophenolate Mofetil (MMF) | Active comparator | Drug: MMFMycophenolate 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 |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (34 listed)
- • Prior therapy with rituximab, tacrolimus or cyclosporine
- Patients who fail screening due to an abnormal laboratory parameter may be rescreened within the next 6 months if the local PI believes that the abnormality was transient and not related to a chronic underlying disease. Rescreening may only occur once and may not occur within 2 weeks of the initial screen failure.
- If a patient has a clinically significant laboratory abnormality, the PI will be asked to define a follow-up plan (timing of repeating the laboratory test and/or additional work-up).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabWe 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 | Drug | Rituximab |
| MMFSubjects randomized to MMF, will continue MMF as scheduled by the investigator | Drug | Mycophenolate Mofetil (MMF) |
Primary outcome
Relapse Free Survival
Time frame: 6 months
1 secondary outcome
Relapse Free at 12 Months
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39513526Larkins 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William Smoyer, MD principal investigator
Nationwide Children's Hospital
Laurence Greenbaum, MD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab and MMF in people with Frequent Relapsing Nephrotic Syndrome and Steroid Dependent Nephrotic Syndrome, run by Nationwide Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse Free Survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02390362, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2019; AzTrials last refreshed its copy on 6 Nov 2026.