Steroid-Dependent Nephrotic SyndromePhase 3RITURNS IINCT03899103
Compare Efficacy and Safety of Repeated Courses of Rituximab to That of Maintenance Mycophenolate Mofetil Following Single Course of Rituximab Among Children With Steroid Dependent Nephrotic Syndrome
A Phase 3 study testing Rituximab and Mycophenolate Mofetil in people with Steroid-Dependent Nephrotic Syndrome, run by Nilratan Sircar Medical College at 1 site in India.
Trial summary
The aim of the RITURNS II study is to evaluate the efficacy and safety of Repeat courses of Rituximab to that of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 24 months among Children with Steroid Dependent Nephrotic Syndrome (SDNS). Read more about this study
- Who is it for?
- Ages 3 to 16 years
- Conditions the study is for
- Steroid-Dependent Nephrotic Syndrome
- What is being tested?
- Rituximab and Mycophenolate Mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteIndia
- Study dates
- 15 May 2019to 24 Dec 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 3 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children between 3 and 16 years with SDNS.
- Minimal Change disease/ FSGS/MesPGN as per Kidney Biopsy report.
- Estimated glomerular filtration rate (eGFR) >80 ml/min per 1.73 m2 at study entry.
- Remission at study entry (Urine albumin nil or trace (or proteinuria <4 mg/m2/h) for 3 consecutive early morning specimens).
- Not received any steroid sparing agent previously.
- Parents willing to give informed written and audiovisual consent.
- Ability to swallow tablet.
Who cannot join
- Known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malignancy, other secondary forms of NS).
- Patients with severe leukopenia (leukocytes <3.0× 1000 cells/mm3), severe anemia (haemoglobin <8.9 g/dl), thrombocytopenia (platelet <100.0 × 1000 cells/mm3) or deranged liver function tests (AST or ALT to >50 IU/L ) at enrolment.
- Known active chronic infection (tuberculosis, HIV, hepatitis B or C).
- Live vaccination within one month prior to screening.
Trial locations and contacts
1 site in 1 country.
India1 site
Nilratan Sircar Medical College and Hospital
Kolkata, West Bengal, 700014
About this study
Official title: Randomized Clinical Trial to Compare Efficacy and Safety of Repeated Courses of Rituximab to That of Maintenance Mycophenolate Mofetil Following Single Course of Rituximab in Maintaining Remission Over 24 Months Among Children With Steroid Dependent Nephrotic Syndrome
The aim of the RITURNS II study is to evaluate the efficacy and safety of Repeat courses of Rituximab to that of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 24 months among Children with Steroid Dependent Nephrotic Syndrome (SDNS).
Read the detailed description
The vast majority of children with idiopathic nephrotic syndrome respond well to corticosteroid treatment. However, as many as 70% experience at least one relapse, and 30% develop a more complicated course with frequent relapses (FRNS) with or without steroid dependency (SDNS). Extended steroid exposure in these children often results in long-term complications. The management of patients with SDNS is challenging and expensive. Relapses may lead to serious complications, e.g. related to anasarca, hypertension, life threatening infections (peritonitis, pneumonia, meningitis), thrombosis and malnutrition. Repeated courses or even continuous steroid treatment lead to considerable medication related toxicity and morbidity.
The goal of treatment is to reduce the rate of relapses, the cumulative dose of corticosteroids, and the incidence of serious complications. Various prospective studies suggest that Rituximab, a B cell depleting monoclonal antibody, could be a safe and effective alternative to steroid or immunosuppressants to achieve and maintain remission in this population. Single rituximab infusion have been shown to be efficacious for 6 to 12 months and the side effect profile observed to date is very benign but after 6-8 months there was relapse due to regeneration of B-lymphocytes, hence for maintenance of remission MMF has been considered. In spite of good initial response, rituximab responders always remain prone to further relapse with regeneration of B lymphocytes, necessitating either repeat course of rituximab or addition of another steroid-sparing immunosuppressant. Reports suggest efficacy of rituximab may vary depending on disease pathology, clinical course, and simultaneous use of other immunosuppressants.
The aim of the RITURNS II study is to evaluate the efficacy and safety of Repeat courses of Rituximab to that of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 24 months among Children with Steroid Dependent Nephrotic Syndrome (SDNS).
- Conditions
- Steroid-Dependent Nephrotic Syndrome
- Being tested
- Rituximab, Mycophenolate Mofetil
- 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
First course Course Rituximab at Randomization.
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards
| Study group | Role | What they receive |
|---|---|---|
| Repeated Courses of Rituximab Only | Experimental | First course Course Rituximab at Randomization. Prophylactic 2nd and 3rd course rituximab re-administration will be done at 8 months and 16 months of follow-up if B cell count normalize. Receives: Drug: Rituximab |
| Rituximab and Mycophenolate Mofetil | Active comparator | First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Receives: Drug: Rituximab; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the time to first relapse or death (whichever occurs first) till end of study (follow-up phase of 24 months)
Measured: 24 months
Secondary outcomes (3)
Cumulative prednisolone requirement (mg/kg/yr) over the first 12 and 24 months, respectively.
Measured: 12 and 24 months
Number and severity of adverse events
Measured: 0-24 months
Number of relapses within months 0-24, 0-12 and 12-24, respectively
Measured: months 0-24, 0-12 and 12-24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2019
- Study start15 May 2019
- Primary completion5 Sep 2023
- Study completion24 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Steroid-Dependent Nephrotic SyndromeStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nilratan Sircar Medical College
- Sponsor type
- Other government
- Collaborators
- Heidelberg University
- Responsible party
- Principal investigator, Dr. Biswanath Basu, Nilratan Sircar Medical College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03899103
- Sponsor's protocol ID
- PednephroRCT/NMC/586
- Acronym
- RITURNS II
- Status last verified
- Dec 2024
- First submitted
- 1 Apr 2019
- Last updated
- 17 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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 39513526Chan EY, Yap DY, Colucci M, Ma AL, Parekh RS, Tullus K. Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):533-548. doi: 10.2215/CJN.08570722. Epub 2023 Feb 22.
PubMed 36456193Basu B, Preussler S, Sander A, Mahapatra TKS, Schaefer F. Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome. BMC Nephrol. 2020 Nov 30;21(1):520. doi: 10.1186/s12882-020-02153-5.
PubMed 33256621
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial to Compare Efficacy and Safety of Repeated Courses of Rituximab to That of Maintenance Mycophenolate Mofetil Following Single Course of Rituximab in Maintaining Remission Over 24 Months Among Children With Steroid Dependent Nephrotic Syndrome
- ClinicalTrials.gov ID
- NCT03899103
- Acronym / sponsor ID
- RITURNS II / PednephroRCT/NMC/586
- Conditions
- Steroid-Dependent Nephrotic Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Nilratan Sircar Medical CollegeOther government
- Collaborators
- Heidelberg University
- Study start
- 15 May 2019 (actual)
- Primary completion
- 5 Sep 2023 (actual)
- Study completion
- 24 Dec 2023 (actual)
- First posted
- 2 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the RITURNS II study is to evaluate the efficacy and safety of Repeat courses of Rituximab to that of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 24 months among Children with Steroid Dependent Nephrotic Syndrome (SDNS).
Detailed description
The vast majority of children with idiopathic nephrotic syndrome respond well to corticosteroid treatment. However, as many as 70% experience at least one relapse, and 30% develop a more complicated course with frequent relapses (FRNS) with or without steroid dependency (SDNS). Extended steroid exposure in these children often results in long-term complications. The management of patients with SDNS is challenging and expensive. Relapses may lead to serious complications, e.g. related to anasarca, hypertension, life threatening infections (peritonitis, pneumonia, meningitis), thrombosis and malnutrition. Repeated courses or even continuous steroid treatment lead to considerable medication related toxicity and morbidity.
The goal of treatment is to reduce the rate of relapses, the cumulative dose of corticosteroids, and the incidence of serious complications. Various prospective studies suggest that Rituximab, a B cell depleting monoclonal antibody, could be a safe and effective alternative to steroid or immunosuppressants to achieve and maintain remission in this population. Single rituximab infusion have been shown to be efficacious for 6 to 12 months and the side effect profile observed to date is very benign but after 6-8 months there was relapse due to regeneration of B-lymphocytes, hence for maintenance of remission MMF has been considered. In spite of good initial response, rituximab responders always remain prone to further relapse with regeneration of B lymphocytes, necessitating either repeat course of rituximab or addition of another steroid-sparing immunosuppressant. Reports suggest efficacy of rituximab may vary depending on disease pathology, clinical course, and simultaneous use of other immunosuppressants.
The aim of the RITURNS II study is to evaluate the efficacy and safety of Repeat courses of Rituximab to that of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 24 months among Children with Steroid Dependent Nephrotic Syndrome (SDNS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Repeated Courses of Rituximab Only | Experimental | Drug: RituximabFirst course Course Rituximab at Randomization. Prophylactic 2nd and 3rd course rituximab re-administration will be done at 8 months and 16 months of follow-up if B cell count normalize. |
| Rituximab and Mycophenolate Mofetil | Active comparator | Drug: Rituximab, Drug: Mycophenolate MofetilFirst course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. |
Who may qualify
- Ages
- 3 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Children between 3 and 16 years with SDNS.
- Minimal Change disease/ FSGS/MesPGN as per Kidney Biopsy report.
- Estimated glomerular filtration rate (eGFR) >80 ml/min per 1.73 m2 at study entry.
- Remission at study entry (Urine albumin nil or trace (or proteinuria <4 mg/m2/h) for 3 consecutive early morning specimens).
- Not received any steroid sparing agent previously.
Key exclusion criteria (4 listed)
- Known etiology (e.g., lupus erythematosus, IgA nephropathy, amyloidosis, malignancy, other secondary forms of NS).
- Patients with severe leukopenia (leukocytes <3.0× 1000 cells/mm3), severe anemia (haemoglobin <8.9 g/dl), thrombocytopenia (platelet <100.0 × 1000 cells/mm3) or deranged liver function tests (AST or ALT to >50 IU/L ) at enrolment.
- Known active chronic infection (tuberculosis, HIV, hepatitis B or C).
- Live vaccination within one month prior to screening.
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 |
|---|---|---|
| RituximabFirst course Course Rituximab at Randomization. | Drug | Repeated Courses of Rituximab Only, Rituximab and Mycophenolate Mofetil |
| Mycophenolate MofetilAddition of Maintenance Mycophenolate Mofetil from 4 Month onwards | Drug | Rituximab and Mycophenolate Mofetil |
Primary outcome
The primary endpoint is the time to first relapse or death (whichever occurs first) till end of study (follow-up phase of 24 months)
Time frame: 24 months
3 secondary outcomes
Cumulative prednisolone requirement (mg/kg/yr) over the first 12 and 24 months, respectively.
Time frame: 12 and 24 months
Number and severity of adverse events
Time frame: 0-24 months
Number of relapses within months 0-24, 0-12 and 12-24, respectively
Time frame: months 0-24, 0-12 and 12-24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2024.
- 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.
- Derived from this study: PubMed 36456193Chan EY, Yap DY, Colucci M, Ma AL, Parekh RS, Tullus K. Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome. Clin J Am Soc Nephrol. 2023 Apr 1;18(4):533-548. doi: 10.2215/CJN.08570722. Epub 2023 Feb 22.
- Derived from this study: PubMed 33256621Basu B, Preussler S, Sander A, Mahapatra TKS, Schaefer F. Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome. BMC Nephrol. 2020 Nov 30;21(1):520. doi: 10.1186/s12882-020-02153-5.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Mycophenolate Mofetil in people with Steroid-Dependent Nephrotic Syndrome, run by Nilratan Sircar Medical College at 1 site in India.
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 7 inclusion and 4 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: finished, as of the sponsor's last update on 17 Dec 2024. 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 India. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary endpoint is the time to first relapse or death (whichever occurs first) till end of study (follow-up phase of 24 months) (time frame: 24 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 NCT03899103, which also lists 3 linked publications.
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 17 Dec 2024.