Reduce Immunosuppression With Atmp in NS ChildrEn (RACE)
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|ClinicalTrials.gov Identifier: NCT04034316|
Recruitment Status : Enrolling by invitation
First Posted : July 26, 2019
Last Update Posted : August 11, 2020
A phase II open-label, single arm study aimed to ascertain whether infusions of cord-blood mesenchymal stromal cells (CB-MSCs) allow to reduce or suspend the chronic immunosuppressive therapy (IS) in steroid-dependent nephrotic syndrome (SDNS).
We plan to enroll 11 patients aged 3 to 18 with SDNS in remission for at least one month, maintained by either ≥2 immunosuppressive drugs or a calcineurin inhibitor.
Patients are infused with cord-blood allogenic MSC, selected by in-vitro alloreactivity, at a dose of 1.5x10^6/kg on days 0, 14, 21. The immunosuppressive treatment is gradually tapered starting at the first CB-MSC administration, according to the following scheme: 25% following the first administration, 50% following the second administration, and 100% reduction following the third administration.
All patients will be followed-up for 6 months from the last CB-MSC. Study visits are planned at baseline during CB-MSC administrations, 2 weeks (follow-up [FU]1) and 6 weeks (FU2) after the last infusion, and then every 6 weeks. During follow-up, the patients undergo a physical examination (including measurement of height, weight and blood pressure) and laboratory evaluations (urinary protein:urinary creatinine ratio, complete blood count, kidney function, plasma proteins, liver function, triglycerides and cholesterol). In addition, a blood sample is taken for regulatory T lymphocyte quantification, a marker of clinical response to the infusions.
|Condition or disease||Intervention/treatment||Phase|
|Nephrotic Syndrome in Children Steroid-Dependent Nephrotic Syndrome Idiopathic Nephrotic Syndrome||Other: Cord-blood mesenchymal stromal cells||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Open-label Study to Evaluate the Efficacy of Allogeneic Human Cord Blood-derived Mesenchymal Stromal Cells in Maintaining Remission After Immunosuppressive Therapy Withdrawal in Pediatric Patients With Steroid-dependent Nephrotic Syndrome|
|Actual Study Start Date :||November 2, 2018|
|Estimated Primary Completion Date :||June 30, 2021|
|Estimated Study Completion Date :||December 2021|
During the first part of the study, 11 SDNS pediatric patients will receive 3 intravenous infusions of CB-MSCs at the dosage of 1.5 x 10^6/kg at a time interval of 1 to 2 weeks. The ongoing immunosuppressive treatment will be gradually tapered off after the first CB-MSC administration, as follows:
In the case that the hypothesis that P ≥ 0.600 is rejected and therefore the second part of the study will be required, 11 additional pediatric patients with SDNS will be treated with 3 intravenous infusions of CB-MSCs at the dosage of 2x10^6/kg at a time interval of 1 to 2 weeks.
Other: Cord-blood mesenchymal stromal cells
The product is packaged in bags suitable for the cryopreservation of cell products. Before administration the cells must be thawed and diluted in an appropriate vol:vol solution: made by saline 78%, human albumin 10%, Acyl-CoA dehydrogenase-A (ACD-A) 12%.
- The percentage of patients without nephrotic syndrome recurrence after complete withdrawal of immunosuppressive treatment for at least 6 months [ Time Frame: 6 months following completion of the intervention ]The percentage of patients without nephrotic-range proteinuria as measured by the urinary protein to urinary creatinine ratio (uPr/uCr<2) 6 months after completing the intervention
- The percentage of adverse events [ Time Frame: 6 months following completion of the intervention ]As described by the Common Terminology Criteria for Adverse Events
- The time to recurrence of nephrotic syndrome [ Time Frame: Within 6 months from the completion of the intervention ]As measured by the ratio of urinary protein to urinary creatinine
- The percentage of participants achieving a reduction in the immunosuppressive therapy [ Time Frame: 6 months following completion of the intervention ]Reduction of the ongoing immunosuppressive treatment
- The dose of immunosuppressive therapy to prevent further NS relapses [ Time Frame: 6 months following completion of the intervention ]The minimal dose of immunosuppressive therapy necessary to maintain the patient in remission following the therapy
- Reported Quality of Life [ Time Frame: 6 months following completion of the intervention ]Changes in quality of life as reported by the patients and/or parents
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04034316
|Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan|
|Milan, MI, Italy|