Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Autologous Neo-Kidney Augment™ (NKA) in Type 2 Diabetics With Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02836574
Recruitment Status : Recruiting
First Posted : July 19, 2016
Last Update Posted : June 18, 2020
Sponsor:
Collaborator:
CTI Clinical Trial and Consulting Services
Information provided by (Responsible Party):
inRegen

Tracking Information
First Submitted Date  ICMJE June 22, 2016
First Posted Date  ICMJE July 19, 2016
Last Update Posted Date June 18, 2020
Study Start Date  ICMJE September 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
Change in Renal Function [ Time Frame: Through 24 months following last NKA injection ]
eGFR at 24 months after last NKA injection
Original Primary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
Change in Renal Function [ Time Frame: Through 12 months following last NKA injection ]
eGFR at 12 months after last NKA injection
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
Treatment emergent adverse events [ Time Frame: Through 24 months following last NKA injection ]
Treatment emergent adverse events, serial safety laboratory results
Original Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2016)
Treatment emergent adverse events [ Time Frame: Through 12 months following last NKA injection ]
Treatment emergent adverse events, serial safety laboratory results
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Autologous Neo-Kidney Augment™ (NKA) in Type 2 Diabetics With Chronic Kidney Disease
Official Title  ICMJE A Phase 2 Prospective, Randomized, Double-Arm, Deferred Treatment, Open Label, Repeat Dose, Safety and Efficacy Sudy of Autologous Neo-Kidney Augment™ (NKA) in Subjects With Type 2 Diabetes and Chronic Kidney Disease
Brief Summary Multi-center, prospective, open-label, randomized, double-arm, deferred treatment study whereby eligible subjects will be randomized 1:1 after kidney biopsy to receive up to 2 injections of NKA (made from expanded autologous selected renal cells) into the biopsied kidney beginning as soon as NKA can be prepared, or the same series of up to 2 injections given 6 months (+4 weeks) apart beginning 12 months after renal biopsy
Detailed Description

NKA is made from expanded autologous selected renal cells obtained from each individual subject's kidney biopsy. To manufacture NKA, biopsy tissue from each enrolled subject will be sent to Twin City Bio LLC, in whose facilities renal cells will be expanded and SRC selected. SRC will be formulated in a gelatin-based hydrogel at a concentration of 100 x 106 cells/mL, packaged in a 10 mL syringe, and shipped to the clinical site.

Based on preclinical data, the dose of NKA will be 3 x 106 cells/g estimated kidney weight (gKWest). Since the concentration of SRC per mL of NKA is 100 x 106 cells/mL, the dosing volume will be 3.0 mL for each 100 g of kidney weight.

Subjects will be randomized (1:1) to the Active Treatment Group or the Deferred Treatment Group following renal biopsy. Subjects in the Active Treatment Group will receive their first NKA injection as soon as the NKA product is manufactured and shipped to the clinical site. After 6 months (+4 weeks), a second injection will be given, as appropriate. In contrast, subjects in the "Deferred Treatment Group" will undergo a period of observation after renal biopsy. During this time, they will receive contemporaneous, standard-of-care therapy for CKD while undergoing follow-up evaluations every 3 months similar to subjects in the Active Treatment Group. After 12 months , subjects from the Deferred Treatment Group will receive a series of up to two NKA injections given 6 months (+4 weeks) apart, as appropriate. Consequently, the study design includes a randomized control group receiving standard-of-care treatment for the first 12 months and a randomized, active treatment group receiving up to two NKA injections and follow-up evaluations during the same period of time. In addition, each subject's baseline rate of renal decline, based on adequate historical, clinical data obtained 18 months prior to NKA injection, will serve as a comparator for monitoring the rate of progression of renal insufficiency over time.

The rate of progression of renal insufficiency for the Active Treatment Group (assessed via serial measurements of eGFR pre-randomization through 24 months after the last NKA injection) will be compared against that of the Deferred Treatment Group (ie, contemporaneous control group). In addition, each subject's baseline rate of eGFR decline (derived from adequate historical, clinical data) will be compared against the individual subject's rate of eGFR decline through 24 months following the final NKA treatment. The rate of progression of renal insufficiency from subjects (if any) who received a single NKA injection may be compared against that from subjects who received two NKA injections.

Subjects will complete the KDQOL survey, which is a kidney-specific measure of health-related quality of life (ie, Kidney Disease and Quality of Life™ [KDQOL™-36] Version 1) and the EQ-5D-5L. Scores from the Active Treatment Group will be compared against scores from the Deferred Treatment Group. Subjects from the Deferred Treatment Group will comprise the contemporaneous control group for the analysis of KDQOL scores. In addition, each subject's baseline scores will be compared against the individual subject's KDQOL scores obtained through 24 months after the last NKA injection. Additionally, KDQOL scores from subjects who received a single NKA injection may be compared against scores from subjects who received two injections.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetic Chronic Kidney Disease
Intervention  ICMJE Biological: Neo-Kidney Augment (NKA)
Autologous selected renal cells (SRC).
Study Arms  ICMJE
  • Experimental: Immediate Treatment
    Neo-Kidney Augment (NKA) immediate treatment - Patients who are randomized to receive their first treatment of 2 injections of NKA as soon as NKA product is made available.
    Intervention: Biological: Neo-Kidney Augment (NKA)
  • Active Comparator: Delayed Treatment
    Neo-Kidney Augment (NKA) delayed treatment - Patients who are randomized to receive standard of care treatment for the first 12 months after NKA product is made available before receiving 2 injections of NKA.
    Intervention: Biological: Neo-Kidney Augment (NKA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 18, 2019)
80
Original Estimated Enrollment  ICMJE
 (submitted: July 18, 2016)
50
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. The subject is male or female, 30 to 80 years of age on the date of informed consent.
  2. The subject has an established diagnosis of T2DM.
  3. The subject has an established diagnosis of diabetic nephropathy as the underlying cause of renal disease.
  4. The subject has an established diagnosis of CKD not requiring renal dialysis, defined as having an eGFR between 20 and 50 mL/min/1.73m2 inclusive at the Screening Visit and prior to NKA injection.
  5. The subject has blood pressure less than 150/90 at the Screening Visit, prior to renal biopsy, and prior to NKA injection(s). At the time of the biopsy and injections, the subject's BP should not be significantly below the previously recorded stable pressure.
  6. The subject has stable blood pressure and is maintained on a stable anti-hypertensive medication regimen, if treatment for hypertension is necessary. If treatment includes an angiotensin-converting-enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB), that treatment must have been initiated at least 8 weeks prior to renal biopsy. Treatment must be stable during the 6-week period immediately prior to NKA injection. Stable treatment is defined as dose adjustment to no less than one half of the current dosage or to no more than 2 times the current dosage. Dose interruptions up to 7 days due to medical necessity are allowed.
  7. A minimum of 2 measurements of eGFR or sCr should be obtained at least 3 months apart prior to the Screening Visit or within the previous 18 months to define the rate of progression of CKD. The subject should have adequate, historical clinical data to provide a reasonable estimate of the rate of progression of CKD. The Medical Monitor may be consulted to ensure there is sufficient data.
  8. The subject is willing and able to refrain from NSAID consumption (including aspirin) as well as clopidogrel, prasugrel, or other platelet inhibitors during the period beginning 7 days before through 7 days after both the renal biopsy and NKA injection(s).
  9. The subject is willing and able to refrain from consumption of fish oil and platelet aggregation inhibitors, such as dipryridamole (ie, Persantine®), during the period beginning 7 days before through 7 days after both the renal biopsy and NKA injection(s).
  10. The subject is willing and able to cooperate with all aspects of the protocol.
  11. The subject is willing and able to provide signed informed consent.

Exclusion criteria:

  1. The subject has a history of type 1 diabetes mellitus.
  2. The subject has a history of renal transplantation.
  3. The subject has a serum HbA1c level greater than 10% at the Screening Visit.
  4. The subject has uncontrolled diabetes (defined as metabolically unstable by the Investigator).
  5. The subject has hemoglobin levels less than 9 g/dL prior to each NKA injection.
  6. The subject has abnormal coagulation status as measured by activated partial thromboplastin time (APTT), prothrombin time-international normalized ratio (PT-INR), and/or platelet count at the Screening Visit.
  7. The subject has a bleeding disorder(s) or is taking anticoagulants, such as Coumadin® (warfarin) or direct thrombin inhibitors that, in the judgment of the Investigator, would interfere with the performance of study procedures.
  8. The subject has small kidneys (average size less than 9 cm) or has only one kidney, as assessed by ultrasound and/or MRI prior to renal biopsy, unless earlier radiology reports (generated within 1 year of the Screening Visit) are made available to confirm kidney size and number.
  9. The subject has a known allergy or contraindication(s), or has experienced severe systemic reaction(s) to kanamycin or structurally similar aminoglycoside antibiotic(s)
  10. The subject has a history of anaphylactic or severe systemic reaction(s) or contraindication(s) to human blood products or materials of animal origin (eg, bovine, porcine).
  11. The subject is not a good candidate to undergo percutaneous NKA injection, in the judgment of the surgeon or physician who will perform the procedure. This includes individuals who are morbidly obese (defined as BMI greater than 45 kg/m2), have excessive fat surrounding the kidney, or who are otherwise at excessive risk for serious complications.
  12. The subject has a history of severe systemic reaction(s) or any contraindication to local anesthetics or sedatives.
  13. The subject has a clinically significant infection requiring parenteral antibiotics within 6 weeks of NKA injection.
  14. The subject has acute kidney injury or has experienced a rapid decline in renal function during the last 3 months prior to NKA injection.
  15. The subject has any of the following conditions prior to NKA injection: renal tumors, polycystic kidney disease, anatomic abnormalities that would interfere with the NKA injection procedure or evidence of a urinary tract infection.
  16. The subject has incapacitating cardiac and/or pulmonary disorders.
  17. The subject has a history of cancer within the past 3 years (excluding non-melanoma skin cancer and carcinoma in situ of the cervix).
  18. The subject has clinically significant hepatic disease (ALT or AST greater than 3-times the upper limit of normal) as assessed at the Screening Visit.
  19. The subject is positive for active infection with Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV), and/or Human Immunodeficiency Virus (HIV) as assessed at the Screening Visit.
  20. The subject has a history of active tuberculosis (TB) requiring treatment within the past 3 years.
  21. The subject is immunocompromised or is receiving immunosuppressive agents, including individuals treated for chronic glomerulonephritis within 3 months of NKA injection. Note: inhaled corticosteroids and chronic low-dose corticosteroids (less than or equal to 7.5 mg per day) are permitted as are brief pulsed corticosteroids for intermittent symptoms (eg, asthma).
  22. The subject has a life expectancy less than 2 years.
  23. The female subject is pregnant, lactating (breast feeding), or planning a pregnancy during the course of the study. Or, the female subject is of child-bearing potential and is not using a highly effective method(s) of birth control, including sexual abstinence. Or, the female subject is unwilling to continue using a highly-effective method of birth control throughout the duration of the study. Note: A highly effective method of birth control is defined as one that results in a low failure rate (ie, less than one percent per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices IUDs, sexual abstinence, or a vasectomized partner.
  24. The subject has a history of active alcohol and/or drug abuse that, in the judgment of the Investigator, would impair the subject's ability to comply with the protocol.
  25. The subject's health status would, in the judgment of the Investigator, be jeopardized by participating in the study.
  26. The subject has used an investigational product within 3 months prior to NKA injection without receiving written consent from the Medical Monitor.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kelsey Blaze (513) 598-9290 kblaze@ctifacts.com
Contact: William Aronstein, PhD MD (513) 598-9290 baronstein@ctifacts.com
Listed Location Countries  ICMJE Cayman Islands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02836574
Other Study ID Numbers  ICMJE RMCL-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party inRegen
Study Sponsor  ICMJE inRegen
Collaborators  ICMJE CTI Clinical Trial and Consulting Services
Investigators  ICMJE
Study Director: Ashley Johns inRegen
Study Director: Brian Johnston CTI
PRS Account inRegen
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP