NEPHSTROM for Diabetic Kidney Disease

NCT02585622 | Terminated Phase 1 DMC

• 2 other identifiers: NEPHSTROM2016-000661-23
• Study Type: interventional
• Target: 29
• Locations: 3 countries
• Sites: 4

Brief Summary

The study will investigate, primarily, the safety, feasibility and tolerability and, secondarily, the preliminary efficacy of an allogeneic bone marrow-derived Mesenchymal Stromal Cell (MSC) therapy (ORBCEL-M) in study subjects with type 2 diabetes (T2D) and progressive diabetic kidney disease (DKD).

Conditions

Diabetic Kidney Disease

Keywords

Diabetic Kidney Disease; Mesenchymal Stromal Cells (MSC); immune response; allogeneic; disease progression

Outcome Measures

Primary Outcomes (1)

• Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events.

  At each visit overall clinical condition of the patient will be evaluated and any adverse event wil be recorded.

  Changes from baseline to study completion, up to 18 months after cell or placebo infusion.

Secondary Outcomes (18)

• Glomerular filtration rate (GFR)

  Changes from baseline up to 18 months after cell or placebo infusion.

• Urinary Albumin/Creatinine Ratio (ACR)

  Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.

• Urinary albumin excretion (UAE).

  Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.

• Fasting blood glucose (target <126mg/dL)

  Proportion of study participants within target range (<126mg/dL) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).

• HbA1c (target <75mmol/mol or <9%)

  Proportion of study participants within target range (<75mmol/mol or <9%) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).

Study Arms (2)

Bone marrow-derived Mesenchymal Stromal Cells

EXPERIMENTAL

Biological: Mesenchymal Stromal Cells

Cryostor CS10

PLACEBO COMPARATOR

Other: Placebo

Interventions

Mesenchymal Stromal Cells BIOLOGICAL

Cells will be administered intravenously at 3 different doses (80, 160, or 240 x 10\^6, fixed dose) over 10-20 minutes. Volume total of fluid infused: 40 ml

Also known as: Allogeneic Cellular Therapy (NEPHSTROM ORBCEL-M)

Bone marrow-derived Mesenchymal Stromal Cells

Placebo OTHER

Volume total of fluid infused: 40 ml

Also known as: Cryostor CS10

Cryostor CS10

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female ≥ 40 years and \<85 years old. ;
• T2D for 3 or more years under a clinician with mandated responsibility for management of the patients to national guidelines;
• Urinary albumin excretion (UAE) ≥ 60 µg/min (in a 24 hour urine collection) and urine albumin-to-creatinine ratio (UACR) ≥ 88 mg/g (≥ 10 mg/mmol) (in a spot morning urine collection);
• Estimated GFR (eGFR) 30-50 ml/min/1.73 m\^2 by the CKD-EPI equation on 2 or more consecutive measurements at least 30 days apart within the past 6 months;
• A documented decline of eGFR of ≥ -10ml/min/1.73 m\^2 over the past 3 years or documented rate of eGFR decline of ≥ -5 ml/min/1.73 m\^2 year based on 3 or more consecutive readings at least 90 days apart in the past 18 months;
• Lack of suspicion of renal diagnosis other than DKD;
• Willing and able to provide written informed consent.

You may not qualify if:

• Current resting systolic BP ≥ 150 mmHg and current resting diastolic BP ≥ 90 mmHg in a clinical setting, despite treatment with 3 hypertensive agents of different classes (including one diuretic), measured in a quiet environment with morning medications already taken;
• Initiation of a new anti-hypertensive agent within the past 6 months
• Increase the dose of an anti-hypertensive agent by ≥ 100% of the previous dose within the past 3 months
• Current HbA1c \> 75 mmol/mol (\> 9%)
• Initiation of a new hypoglycaemic agent within the past 6 months
• Increase the dose of a hypoglycaemic agent by ≥ 100% of the previous dose within the past 3 months
• Current fasting total cholesterol \> 7 mmol/l
• Current fasting total triglycerides \> 3.5 mmol/l
• Initiation of a new lipid lowering agent within the past 6 months
• Chronic lung or liver disease;
• Cardiovascular events (myocardial infarction, stroke or acute limb ischemia) within 6 months prior to enrolment;
• Current or history within 6 months prior to enrolment of NYHA class III or IV heart failure;
• Other concomitant disease or conditions in the opinion of the investigator that are likely to pose risk to the patient and that would render the patient unsuitable for participation or that could impair patient safety or ability to participate in the study, such as active malignancy;
• Irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
• Positive screening test for clinically significant anti-HLA antibodies. An initial antibody screening with Luminex® multi-antigen beads to detect class I and class II MHC antibodies followed by a Luminex single antigen bead assay to determine the specificity of any antibody detected. Potential study subjects with positive screening for any clinically significant anti-HLA antibody will be excluded and will not be eligible to participate in the NEPHSTROM clinical study (MFI\>1500);

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Leiden University Medical Center: collaborator
• Papa Giovanni XXIII Hospital: collaborator
• Istituto Di Ricerche Farmacologiche Mario Negri: collaborator
• Belfast Health and Social Care Trust: collaborator
• National University of Ireland, Galway, Ireland: collaborator
• University Hospital Birmingham, NHS Foundation Trust, Hospital, Birmingham, UK: collaborator
• NHS Blood and Transplant: collaborator

Study Sites (4)

National University of ireland - Galway University Hospital -Regenerative Medicine Institute

Galway, Ireland

Location

ASST - Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/ Mario Negri Institute for Pharmacological Research - Clinical Research Center for Rare Diseases Aldo e Cele Daccò

Bergamo, BG, 24027, Italy

Location

Belfast Health and Social Care Trust - Belfast City Hospital

Belfast, United Kingdom

Location

University Hospital Birmingham NHS Foundation Trust - Queen Elizabeth Medical Centre

Birmingham, United Kingdom

Location

Related Publications (2)

• Perico N, Remuzzi G, Griffin MD, Cockwell P, Maxwell AP, Casiraghi F, Rubis N, Peracchi T, Villa A, Todeschini M, Carrara F, Magee BA, Ruggenenti PL, Rota S, Cappelletti L, McInerney V, Griffin TP, Islam MN, Introna M, Pedrini O, Golay J, Finnerty AA, Smythe J, Fibbe WE, Elliman SJ, O'Brien T; NEPHSTROM Trial Consortium. Safety and Preliminary Efficacy of Mesenchymal Stromal Cell (ORBCEL-M) Therapy in Diabetic Kidney Disease: A Randomized Clinical Trial (NEPHSTROM). J Am Soc Nephrol. 2023 Oct 1;34(10):1733-1751. doi: 10.1681/ASN.0000000000000189. Epub 2023 Aug 10.

  PMID: 37560967 BACKGROUND

• Lu B, Lerman LO. MSC therapy for diabetic kidney disease and nephrotic syndrome. Nat Rev Nephrol. 2023 Dec;19(12):754-755. doi: 10.1038/s41581-023-00776-z. No abstract available.

  PMID: 37783947 DERIVED

MeSH Terms

Conditions

Diabetic Nephropathies; Disease Progression

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Giuseppe Remuzzi, MD

  ASST Papa Giovanni XXIII, Bergamo, Italy/IRCCS - Mario Negri Institute for Pharmacological Research

  STUDY CHAIR

• Mattew Griffin, MD

  National University of ireland - Galway University Hospital -Regenerative Medicine Institute

  PRINCIPAL INVESTIGATOR

• Paul Cockwell, MD

  University Hospital Birmingham NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Peter Maxwell, MD

  Belfast Health and Social Care Trust - Belfast City Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: October 23, 2015
• Study Start: December 11, 2017
• Primary Completion: November 3, 2022
• Study Completion: January 3, 2024
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); IE (1); IT (1)