Reduce Immunosuppression With Atmp in NS ChildrEn

NCT04034316 | Completed Phase 2 DMC

• 2 other identifiers: AIFA-2016-023648962018-001162-42
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nephrotic Syndrome in Children; Steroid-Dependent Nephrotic Syndrome; Idiopathic Nephrotic Syndrome

Keywords

Mesenchymal Stromal Cells; Steroid Dependent Nephrotic Syndrome in Children; Proteinuria; Immunosuppressive treatment

Outcome Measures

Primary Outcomes (1)

• The percentage of patients without nephrotic syndrome recurrence after complete withdrawal of immunosuppressive treatment for at least 6 months

  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

  6 months following completion of the intervention

Secondary Outcomes (5)

• The percentage of adverse events

  6 months following completion of the intervention

• The time to recurrence of nephrotic syndrome

  Within 6 months from the completion of the intervention

• The percentage of participants achieving a reduction in the immunosuppressive therapy

  6 months following completion of the intervention

• The dose of immunosuppressive therapy to prevent further NS relapses

  6 months following completion of the intervention

• Reported Quality of Life

  6 months following completion of the intervention

Study Arms (1)

MSC

EXPERIMENTAL

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: * 25% reduction of the ongoing immunosuppressive treatment following the first administration; * 50% reduction of the ongoing immunosuppressive treatment following the second administration; * interruption of the ongoing immunosuppressive treatment following the third administration. 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

Interventions

Cord-blood mesenchymal stromal cells OTHER

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%.

MSC

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age between 3 and 18 years;
• Clinical diagnosis of SDNS;
• Disease remission maintained by chronic therapy (at least 6 months) with either:
• Use of a combination of 2 or more immunosuppressive drugs
• use of 1 of the calcineurin inhibitors (Cyclosporin or Tacrolimus);
• Absence of proteinuria (PrU/CrU \< 0.2 mg/mg) for at least 1 month;
• eGFR greater than or equal to 70 ml/min/1.73 m\^2;
• Written informed consent from parents or guardians and the child when possible

You may not qualify if:

• Age \< 3 years or \> 19 years;
• Resistant/refractory NS;
• Presence of genetic mutations associated with NS;
• eGFR less than 70 ml/min/1.73m2;
• Thrombophilic condition;
• Pregnancy or lactating;
• Evidence of an uncooperative attitude;
• Any evidence that the patient will be unable to complete the trial follow-up.

Sponsors & Collaborators

• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: lead
• Cell Factory Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico: collaborator
• Laboratorio Sperimentale di Immunologia e Trapianti, Oncoematologia Pediatrica, Fondazione IRCCS Policlinico S. Matteo, Pavia: collaborator

Study Sites (1)

Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan

Milan, MI, Italy

Location

MeSH Terms

Conditions

Nephrotic Syndrome; Nephrosis, Lipoid; Proteinuria

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Open lable, single arm

Study Record Dates

• First Submitted: July 25, 2019
• First Posted: July 26, 2019
• Study Start: November 2, 2018
• Primary Completion: March 31, 2023
• Study Completion: August 31, 2023
• Last Updated: September 28, 2023

Record last verified: 2023-09

Locations

IT (1)