E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE |
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E.1.1.1 | Medical condition in easily understood language |
TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of up to 2 REACT injections given 3 months apart and delivered percutaneously into biopsied and non-biopsied contralateral kidneys on renal function in participants with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of up to 2 REACT injections given 3 months apart and delivered percutaneously into biopsied and non-biopsied contralateral kidneys on renal function in participants with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Unless otherwise noted, participants must satisfy each inclusion criterion to participate in the study. Inclusion criteria will be assessed at the Screening Visit. 1. The participant is male or female, 30 to 80 years of age on the date of informed consent. 2. The participant has a clinical diagnosis of T2DM in their health record. 3. The participant has a clinical diagnosis of diabetic nephropathy as the underlying cause of renal disease (diagnosis does not have to be confirmed via renal biopsy) in their health record. 4. The participant has a serum glycosylated hemoglobin (HbA1c) less than 10% at the Screening Visit. 5. The participant has a documented clinical diagnosis of an eGFR greater than or equal to 20 and less than or equal to 44 mL/min/1.73m2, not requiring renal dialysis. 6. The participant has a urinary albumin-to-creatinine ratio (UACR) of greater than or equal to 300 and less than or equal to 5,000 mg/g. 7. The participant has stable blood pressure and is maintained on a stable antihypertensive medication regimen if treatment for hypertension is necessary. If treatment contains an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB), that treatment must be the maximum tolerated daily dose for at least 8 weeks prior to screening or if the treatment includes a sodium glucose cotransporter 2 inhibitor (SGLT2i) or mineralocorticoid receptor antagonists (MRA) at any dose, is stable for at least 8 weeks prior to screening. 8. The participant agrees and is able to refrain from nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, and clopidogrel, prasugrel, dipyridamole, or other platelet aggregation inhibitors during the period beginning 7 days before through 7 days following the percutaneous renal biopsy and REACT injection(s). 9. The participant agrees and is able to refrain from oral ingestion of fish oil supplements during the period beginning 7 days before through 7 days following the percutaneous renal biopsy and REACT injection(s). 10. The participant is willing and able to cooperate with all aspects of the protocol. 11. The participant is willing and able to provide signed informed consent.
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E.4 | Principal exclusion criteria |
Participants who satisfy any exclusion criterion listed below are not eligible to participate in the study. Exclusion criteria will be assessed at the Screening Visit. 1. The participant has a history of type 1 diabetes mellitus. 2. The participant has a history of renal transplantation. 3. The participant has a mean systolic blood pressure greater than or equal to 140 mmHg and/or mean diastolic blood pressure greater than or equal to 90 mmHg at screening, across 3 measurements while seated. 4. The participant has hemoglobin levels less than 10 g/dL and is not responsive to the standard medical intervention for CKD-related anemia prior to randomization. 5. The participant appears to be at possibly increased risk of either thromboembolism or bleeding because of abnormal results at the Screening Visit and within 12 weeks prior to Screening Visit for any of the following tests: (see protocol for full details). 6. The participant has a bleeding disorder(s) or is maintained on any anticoagulant agents, including fractionated heparin preparations, Coumadin® (warfarin), or direct thrombin inhibitors that cannot be discontinued for 7 days before and 7 days after biopsy or injections. 7. The participant has a known allergy or contraindication(s), has experienced severe systemic reaction(s), to kanamycin/structurally similar aminoglycoside antibiotic(s), which may be a manufacturing process residual, or has a known hypersensitivity to dimethyl sulfoxide. 8. The participant has a history of anaphylactic or severe systemic reaction(s) or contraindication(s) to blood transfusions, Dextran-40, or bovine products. 9. The participant is not a good candidate to undergo percutaneous REACT injection, in the judgment of the proceduralist or physician who will perform the procedure. This includes confirming the participant has contraindications for undergoing the procedure based on depth of the kidney, positioning limitations and if the kidney is more than 15 cm from the skin surface to kidney capsule, small kidneys (average size less than 9 cm), or has only one kidney. 10. The participant has a history of severe systemic reaction(s) or any contraindication to local anesthetics or sedatives. 11. The participant has been diagnosed with acute kidney injury within 3 months of the Screening Visit. 12. The participant has any of the following conditions: Autosomal dominant and recessive polycystic kidney disease, focal segmental glomerulosclerosis, vasculitis related CKD, IgA nephropathy and other immune modulated nephropathies, drug-induced or hypertension related CKD and other types of CKD or anatomic variants as determined by the Principal Investigator that would interfere with biopsy and REACT injection procedure (such as horseshoe kidney variant and unexplained hydronephrosis), any other documented renal pathology that would interfere with the REACT injection procedure. 13. Myocardial infarction, unstable angina, revascularization procedure (e.g. stent or bypass graft surgery), or cerebrovascular accident within 12 weeks before randomization, or a revascularization procedure is planned during the trial. 14. Current or history of heart failure of New York Heart Association (NYHA) Class IV cardiac disease (The Criteria Committee of the New York Heart Association). 15. ECG findings within 12 weeks before randomization that would require urgent diagnostic evaluation or intervention (e.g., new clinically important arrhythmia or conduction disturbance). 16. The participant has a history of malignancy within the past 3 years (exceptions: basal cell carcinomas of the skin and carcinoma of the cervix in situ, or a malignancy that in the opinion of the Investigator, along with the Medical Monitor, is considered treated with minimal risk of recurrence). 17. The participant has documented clinical diagnosis of chronic hepatic disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] greater than 3 times the upper limit of normal) at the Screening Visit. 18. The participant has a positive test for the Hepatitis B surface antigen, a positive test for Hepatitis C antibodies, a positive test for Human Immunodeficiency Virus antibodies, or a positive test for an active syphilis infection. 19. The participant has a documented clinical diagnosis of active tuberculosis (TB) requiring treatment. 20. The participant is immunocompromised or is receiving immunosuppressive agents, including individuals treated for chronic glomerulonephritis within 3 months of the Screening Visit. Please refer to the protocol for more details |
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E.5 End points |
E.5.1 | Primary end point(s) |
The time from first injection to the earliest of: • At least 40% reduction in eGFR, using the 2009 CKD-EPI serum creatinine equation, sustained for 30 days or • eGFR <15 mL/min/1.73m² using the 2009 CKD-EPI serum creatinine equation, sustained for 30 days and/or chronic dialysis, and/or renal transplant or • Renal or cardiovascular death. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Treatment-emergent adverse events, defined as AEs or SAEs that first appear during or after the kidney biopsy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
scripted sham-controlled intervention study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
scripted sham-controlled intervention study |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Chile |
Colombia |
Malaysia |
Singapore |
Brazil |
India |
Serbia |
Thailand |
Austria |
Belgium |
France |
Italy |
Portugal |
Spain |
Türkiye |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last patient last visit occurs. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |