Frequently Relapsing Nephrotic SyndromePhase 3NCT04531865
Randomized Trial Evaluating Mycophenolate Mofetil in Children With Nephrotic Syndrome After Rituximab Treatment
A Phase 3 study testing Rituximab and Mycophenolate Mofetil in people with Frequently Relapsing Nephrotic Syndrome and Steroid-Dependent Nephrotic Syndrome, run by Children's Hospital of Fudan University at 4 sites in China.
Trial summary
The aim of this study is to evaluate the efficacy and safety of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 12 months among Children with frequently-relapsing or steroid-dependent nephrotic syndrome Read more about this study
- Who is it for?
- Ages 1 year to 16 years
- Conditions the study is for
- Frequently Relapsing Nephrotic Syndrome, Steroid-Dependent Nephrotic Syndrome
- What is being tested?
- Rituximab and Mycophenolate Mofetil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 4 sitesChina
- Study dates
- 1 Jan 2021to 1 Oct 2022
- 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 1 year to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children between 1 and 16 years with Frequently-relapsing or Steroid-dependent Nephrotic Syndrome
- Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
- Remission at study entry
- Patients in whom ≥5 CD20-positive cells/μL are observed in the peripheral blood.
- Parents willing to give informed written and audiovisual consent.
Who cannot join
- Patients who have been diagnosed with nephritic- NS, such as immunoglobulin A(IgA) nephropathy, prior to assignment or in whom secondary NS is suspected.
- Patients showing one of the following abnormal clinical laboratory values:
- 1) Leukocytes < 3000/μL. 2) Neutrophils < 1500/μL. 3) Platelets < 50,000/μL. 4) Alanine aminotransferase (ALT) > 2.5× upper limit of normal value. 5) Aspartate aminotransferase (AST) > 2.5× upper limit of normal value. 6) Positive for hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, or hepatitis C virus (HCV) antibody. 7) Positive for HIV antibody.
- 3. Patients meeting one of the following infection criteria:
- 1) Presence or history of severe infections within 6 months prior to assignment.2) Presence or history of opportunistic infections within 6 months prior to assignment.3) Presence of active tuberculosis.4) Patients with a history of tuberculosis or in whom tuberculosis is suspected.5) Presence or history of active hepatitis B or hepatitis C or hepatitis B virus carrier.6) Presence of human immunodeficiency virus (HIV) infection.
- 4. Presence or history of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia (findings observed under Grade 4 of the Common Terminology Criteria for Adverse Events (CTCAE)).
Show all 14Show fewer
- 5. Presence or history of autoimmune diseases or vascular purpura.
- 6. Presence or history of malignant tumor.
- 7. History of organ transplantation.
- 8. History of drug allergies to methylprednisolone, acetaminophen, cetirizine, mycophenolate mofetil,rituximab, or any of the above drugs
- 9. Uncontrollable hypertension.
- 10. Having received a live vaccine within 4 weeks prior to enrollment.
- 11. Patients who do not agree with contraception during the study period.
- 12. Judged inappropriate for this study by the treating or study physicians.
Trial locations and contacts
4 sites in 1 country.
China4 sites
Children's hospital of Fudan university
Shanghai, Shanghai Municipality, 200000
Shanghai Children's Hospital
Shanghai
Shanghai Children's Medical Center
Shanghai
Xinhua Hospital, Shanghai Jiaotong University School of Medicine
Shanghai
About this study
Official title: Efficacy and Safety of Mycophenolate Mofetil as Maintenance Therapy After Rituximab Treatment in Childhood-onset, Frequently-relapsing or Steroid-dependent Nephrotic Syndrome: a Multicenter Double-blind, Randomized, Placebo-controlled Trial
The aim of this study is to evaluate the efficacy and safety of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 12 months among Children with frequently-relapsing or steroid-dependent nephrotic syndrome
Read the detailed description
The results of multiple observational studies and randomized control trials have shown that Rituximab, a chimeric monoclonal antibody against the cluster of differentiation antigen 20 (CD20) antigen on B cells, is safe and effective for children with complicated steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) without corticosteroid or immunosuppressive therapy. Single rituximab infusion has been shown to be efficacious for 6 to 12 months, the reported median relapse-free period was 9 months. Our previous study found that Mycophenolate mofetil can further improve the sustained remission time.
All patients will be treated with 2 doses of Rituximab 375 mg/m2 iv at time 0 and 7 days. Addition of Maintenance Mycophenolate Mofetil or placebo from 4 Month onwards. The expected duration of the follow-up is 12 months, consisting of 12 visits.
- Being tested
- Rituximab, Mycophenolate Mofetil, Placebo tablets matching 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
Also called Rituximab Biosimilar HLX01
Rituximab: 375 mg/m2 intravenously on day 0 and day 7
Also called Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）
Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day，BID. Total duration : 8 months.
Placebo tablets matching Mycophenolate MofetilDrug
Addition of Maintenance Placebo tablets matching Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day，BID. Total duration : 8 months.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab and Mycophenolate Mofetil | Experimental | First course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Receives: Drug: Rituximab; Drug: Mycophenolate Mofetil |
| Rituximab Only | Placebo comparator | First course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards. Receives: Drug: Rituximab; Drug: Placebo tablets matching Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year relapse-free survival rate
The rate of no relapse within 1 year
Measured: 1-year period after randomization
Secondary outcomes (6)
The concentration for MPA-area under curve(AUC)
Blood concentrations of mycophenolic acid (MPA)
Measured: At 48 weeks
Proportion of patients with a relapse
The proportion of patients with relapse
Measured: 6 months period after randomization
Time to relapse (days)
Number of days from randomization to occurrence of first relapse
Measured: 1-year period after randomization
B-Cell Recovery Time
Time to the first detection of CD19+ cells above 1% of total CD45+ lymphocytes after CD19+ cell depletion
Measured: 1-year period after randomization
Change in growth velocity
The standard deviation scores (SDS) for height at 12th month minus that of randomization.
Measured: 1-year period after randomization
adverse events
It is a binary variable (1/0). The varibale would be setted as "1" if any adverse events occours including early infusion termination, acute infusion reaction Infection, pulmonary fibrosis, encephalopathy, neutropenia. Adverse events graded according to Common Terminology Criteria For Adverse Events (NCI-CTCAE v4.03)
Measured: 1-year period after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2020
- Study start1 Jan 2021 (estimated)
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Oct 2022 (estimated)
Why it stopped: lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frequently Relapsing Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of Fudan UniversityThe 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Collaborators
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Medical Center, Shanghai Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Xu Hong, PhD.MD., Principal investigator, Children's Hospital of Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04531865
- Sponsor's protocol ID
- FRSDRM
- Status last verified
- Dec 2020
- First submitted
- 26 Aug 2020
- Last updated
- 29 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Mycophenolate Mofetil as Maintenance Therapy After Rituximab Treatment in Childhood-onset, Frequently-relapsing or Steroid-dependent Nephrotic Syndrome: a Multicenter Double-blind, Randomized, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT04531865
- Acronym / sponsor ID
- FRSDRM
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital of Fudan UniversityUniversity, hospital or other
- Collaborators
- Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Children's Medical Center, Shanghai Children's Hospital
- Study start
- 1 Jan 2021 (estimated)
- Primary completion
- 1 Sep 2022 (estimated)
- Study completion
- 1 Oct 2022 (estimated)
- First posted
- 31 Aug 2020 (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 this study is to evaluate the efficacy and safety of maintenance Mycophenolate Mofetil following single course of Rituximab in maintaining remission over 12 months among Children with frequently-relapsing or steroid-dependent nephrotic syndrome
Detailed description
The results of multiple observational studies and randomized control trials have shown that Rituximab, a chimeric monoclonal antibody against the cluster of differentiation antigen 20 (CD20) antigen on B cells, is safe and effective for children with complicated steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) without corticosteroid or immunosuppressive therapy. Single rituximab infusion has been shown to be efficacious for 6 to 12 months, the reported median relapse-free period was 9 months. Our previous study found that Mycophenolate mofetil can further improve the sustained remission time.
All patients will be treated with 2 doses of Rituximab 375 mg/m2 iv at time 0 and 7 days. Addition of Maintenance Mycophenolate Mofetil or placebo from 4 Month onwards. The expected duration of the follow-up is 12 months, consisting of 12 visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab and Mycophenolate Mofetil | Experimental | Drug: Rituximab, Drug: Mycophenolate MofetilFirst course Course Rituximab at Randomization. Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. |
| Rituximab Only | Placebo comparator | Drug: Rituximab, Drug: Placebo tablets matching Mycophenolate MofetilFirst course Course Rituximab at Randomization. Addition of Maintenance Placebo tablets matching Mycophenolate mofetil from 4 Month onwards. |
Who may qualify
- Ages
- 1 year to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Children between 1 and 16 years with Frequently-relapsing or Steroid-dependent Nephrotic Syndrome
- Estimated glomerular filtration rate (eGFR) ≥90 ml/min per 1.73 m2 at study entry.
- Remission at study entry
- Patients in whom ≥5 CD20-positive cells/μL are observed in the peripheral blood.
- Parents willing to give informed written and audiovisual consent.
Key exclusion criteria (14 listed)
- Patients who have been diagnosed with nephritic- NS, such as immunoglobulin A(IgA) nephropathy, prior to assignment or in whom secondary NS is suspected.
- Patients showing one of the following abnormal clinical laboratory values:
- 1) Leukocytes < 3000/μL. 2) Neutrophils < 1500/μL. 3) Platelets < 50,000/μL. 4) Alanine aminotransferase (ALT) > 2.5× upper limit of normal value. 5) Aspartate aminotransferase (AST) > 2.5× upper limit of normal value. 6) Positive for hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, or hepatitis C virus (HCV) antibody. 7) Positive for HIV antibody.
- 1) Presence or history of severe infections within 6 months prior to assignment.2) Presence or history of opportunistic infections within 6 months prior to assignment.3) Presence of active tuberculosis.4) Patients with a history of tuberculosis or in whom tuberculosis is suspected.5) Presence or history of active hepatitis B or hepatitis C or hepatitis B virus carrier.6) Presence of human immunodeficiency virus (HIV) infection.
- 4. Presence or history of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia (findings observed under Grade 4 of the Common Terminology Criteria for Adverse Events (CTCAE)).
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 |
|---|---|---|
| RituximabAlso: Rituximab Biosimilar HLX01Rituximab: 375 mg/m2 intravenously on day 0 and day 7 | Drug | Rituximab Only, Rituximab and Mycophenolate Mofetil |
| Mycophenolate MofetilAlso: Mycophenolate Mofetil Dispersible tablets（CYCOPIN®）Addition of Maintenance Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day，BID. Total duration : 8 months. | Drug | Rituximab and Mycophenolate Mofetil |
| Placebo tablets matching Mycophenolate MofetilAddition of Maintenance Placebo tablets matching Mycophenolate Mofetil from 4 Month onwards. Dose: 20~30mg/kg/day，BID. Total duration : 8 months. | Drug | Rituximab Only |
Primary outcome
1-year relapse-free survival rate
Time frame: 1-year period after randomization
The rate of no relapse within 1 year
6 secondary outcomes
The concentration for MPA-area under curve(AUC)
Time frame: At 48 weeks
Proportion of patients with a relapse
Time frame: 6 months period after randomization
Time to relapse (days)
Time frame: 1-year period after randomization
B-Cell Recovery Time
Time frame: 1-year period after randomization
Change in growth velocity
Time frame: 1-year period after randomization
adverse events
Time frame: 1-year period after randomization
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
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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.
Xu Hong, PhD.MD. principal investigator
Children's Hospital of Fudan University
4 sites 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 Frequently Relapsing Nephrotic Syndrome and Steroid-Dependent Nephrotic Syndrome, run by Children's Hospital of Fudan University at 4 sites in China.
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 5 inclusion and 14 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: withdrawn, as of the sponsor's last update on 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China. 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. Some participants in this study may receive a placebo. 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 was withdrawn before enrolling participants, so there are no results.
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?
1-year relapse-free survival rate (time frame: 1-year period after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Dec 2020.