NEPHSTROM for Diabetic Kidney Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT02585622
• Date of registration: 22/10/2015
• Prospective Registration: Yes
• Primary sponsor: Mario Negri Institute for Pharmacological Research
• Public title: NEPHSTROM for Diabetic Kidney Disease NEPHSTROM
• Scientific title: Novel Stromal Cell Therapy for Diabetic Kidney Disease (NEPHSTROM Study)
• Date of first enrolment: December 11, 2017
• Target sample size: 48
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02585622
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Ireland, Italy, United Kingdom

Contacts

• Name: Peter Maxwell, MD
• Affiliation: Belfast Health and Social Care Trust - Belfast City Hospital

• Name: Mattew Griffin, MD
• Affiliation: National University of ireland - Galway University Hospital -Regenerative Medicine Institute

• Name: Paul Cockwell, MD
• Affiliation: University Hospital Birmingham NHS Foundation Trust

• Name: Giuseppe Remuzzi, MD
• Affiliation: ASST Papa Giovanni XXIII, Bergamo, Italy/IRCCS - Mario Negri Institute for Pharmacological Research

Key inclusion & exclusion criteria

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:

1. 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;

2. Initiation of a new anti-hypertensive agent within the past 6 months

3. 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:

4. Current HbA1c > 75 mmol/mol (> 9%)

5. Initiation of a new hypoglycaemic agent within the past 6 months

6. Increase the dose of a hypoglycaemic agent by = 100% of the previous dose within the
past 3 months

Exclusion criteria related to dyslipidaemia:

7. Current fasting total cholesterol > 7 mmol/l

8. Current fasting total triglycerides > 3.5 mmol/l

9. Initiation of a new lipid lowering agent within the past 6 months

Other exclusion criteria:

10. Chronic lung or liver disease;

11. Cardiovascular events (myocardial infarction, stroke or acute limb ischemia) within 6
months prior to enrolment;

12. Current or history within 6 months prior to enrolment of NYHA class III or IV heart
failure;

13. 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;

14. Irreversible disease or condition for which 6-month mortality is estimated to be
greater than 50%;

15. 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);

16. 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;

17. 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.

18. Pregnancy or lactating;

19. Participation in other investigational medicinal product (IMP) trials within 30 days
before the inclusion or concurrent to this study (18 month follow-up);

20. Inability to understand the potential risks and benefits of the study;

21. Legal incapacity.



Age minimum: 40 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diabetic Kidney Disease

Intervention(s)

Other: Placebo

Biological: Mesenchymal Stromal Cells

Primary Outcome(s)

Number and severity of all pre-specified infusion-associated events and the overall number and frequency of adverse events. [Time Frame: Changes from baseline to study completion, up to 18 months after cell or placebo infusion.]

Secondary Outcome(s)

Arterial blood pressure (the target value <130/80 mmHg) [Time Frame: Proportion of study participants within target range (<130/80 mmHg)at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).]

LDL cholesterol (target <100 mg/dl) [Time Frame: Proportion of study participants within target range (<100 mg/dl) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).]

Urinary Albumin/Creatinine Ratio (ACR) [Time Frame: Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.]

Cost-effectiveness of cell therapy [Time Frame: Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.]

Glomerular filtration rate (GFR) [Time Frame: Changes from baseline up to 18 months after cell or placebo infusion.]

Total cholesterol (target <200 mg/dl) [Time Frame: Proportion of study participants within target range (<200 mg/dl) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).]

Quality of life [Time Frame: Changes from baseline to 1,3,6,12 and 18 months after cell or placebo infusion.]

Fasting blood glucose (target <126mg/dL) [Time Frame: 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%) [Time Frame: 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).]

Triglycerides (target <170 mg/dl) [Time Frame: Proportion of study participants within target range (<170 mg/dl) at baseline and at each time point (day 1, day 7, month 1,3,6,12,18 after cell or placebo infusion).]

Inflammation and fibrosis related soluble mediators [Time Frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.]

Anti-HLA antibody development [Time Frame: Changes from baseline to 3,12 and 18 months after cell or placebo infusion.]

Urinary albumin excretion (UAE). [Time Frame: Changes from baseline at 6 months and then every six months to study completion,up to 18 months after cell or placebo infusion.]

Serum/plasma concentrations (ng/ml) of biomarkers of CKD progression. [Time Frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.]

Proportion/total number of circulating T cells, B cells, NK cells, monocytes, dendritic cells [Time Frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.]

Serum/plasma concentrations (pg/ml) of biomarkers of inflammation. [Time Frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.]

Urine concentrations (pg/ml adjusted to urine creatinine concentration) of biomarkers of inflammation. [Time Frame: Changes from baseline to 7 days, 1,6,12 and 18 months after cell or placebo infusion.]

Secondary ID(s)

2016-000661-23

NEPHSTROM

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

NHS Blood and Transplant

Leiden University Medical Center

National University of Ireland, Galway, Ireland

Belfast Health and Social Care Trust

IRCCS - Istituto di Ricerche Farmacologiche Mario Negri - Bergamo, Italy

ASST Papa Giovanni XXIII, Bergamo, Italy

University Hospital Birmingham, NHS Foundation Trust, Hospital, Birmingham, UK