NEPHSTROM for Diabetic Kidney Disease

Mario Negri Institute for Pharmacological Research

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Diabetic Kidney Disease

Treatments

Biological: Mesenchymal Stromal Cells

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02585622

2016-000661-23 (EudraCT Number)

NEPHSTROM

Details and patient eligibility

About

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).

Enrollment

29 patients

Sex

All

Ages

40 to 85 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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

Exclusion criteria related to glycaemic control:
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

Exclusion criteria related to dyslipidaemia:
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

Other exclusion criteria:
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);
History or presence of any medical condition or disease which, in the opinion of the Investigator may place the participant at unacceptable risk for study participation;
Childbearing potential without use of effective acceptable methods of contraception. Women of childbearing potential can only be included in the study if a pregnancy test is negative at the screening visit (V1) and at baseline visit (V2) if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least two effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL or have had surgical treatment such as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
Pregnancy or lactating;
Participation in other investigational medicinal product (IMP) trials within 30 days before the inclusion or concurrent to this study (18 month follow-up);
Inability to understand the potential risks and benefits of the study;
Legal incapacity.