Mesenchymal Stromal Cells in Living Donor Kidney Transplantation

A Double-blind, Randomized, Controlled Dose Escalation Trial of Autologuous Mesenchymal Stromal Cells in Living Donor Kidney Transplant Recipients

Kidney transplantation is a good treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients receive induction therapy and immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. This research study will evaluate the safety and activity of mesenchymal stromal stem cells (MSCs) infusion compared to saline-only infusion in reducing the immune suppression necessary to achieve optimal renal function in renal transplant recipients. All participants will receive routine care: basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids.

The study is a double-blind, randomized, controlled, dose-escalation and safety study of the investigational product, autologous MSCs, to be assessed for inducing immune suppression in living donor kidney transplant recipients as compared to saline, the placebo infusion. The investigator will obtain exploratory immune response markers to estimate the effect of autologous MSCs on the T- and B-cell response following living donor kidney transplantation. The usual routine care supportive drugs will be given to all: corticosteroids during induction, the calcineurin inhibitor tacrolimus (Prograf®, Astellas Pharma), and mycophenolate mofetil (Cellcept®, Genentech) for maintenance therapy. All subjects will receive basiliximab (Simulect®, Novartis), a standard drug used to induce immune suppression.

Up to 24 patients will be enrolled at the Houston Methodist Hospital. Safety analyses will be conducted after the first 4 subjects have been enrolled and completed the first 30-90 days posttransplant, with subject 2 enrolled 30 days after subject 1 and subject 3 enrolled 30 days after subject 2 (eg, a 30-day window between subject enrollment days). If no safety signal has been detected, the next group of 4 subjects will be enrolled using no less than a 2-week enrollment window from subject 5, 2 weeks from subject 6, and so on. Subjects will be evaluated in the same manner until 8 subjects in the final dosing group have completed 90 days or a decision to stop the study has occurred, whichever comes first. Each subsequent dosing group will begin with a 30-day window of evaluation between subjects enrolled for the first 4 subjects enrolled in the group. If no adverse safety signal has been detected in the first 4 cases in that dosing group, the next 4 subjects enrolled will have a 2-week evaluation window between enrollments. This early evaluation approach will allow for the assessment of the inflammatory period occurring after transplantation. A final safety review will occur at the end of the study and a report will be written.

The study will provide information needed to select a MSC dose level to be used in subsequent clinical trials and to inform the design of subsequent trials.

Inclusion Criteria:

1. Males and females from 18 to 65 years of age

2. Planned to receive a primary kidney transplant from a living donor

3. Low immunologic risk defined as

   1. No history of current or historical antidonor human leukocyte antigen (HLA) antibodies (DSA)
   2. Panel of Reactive Antibodies (PRA) <20%, historical

4. Low risk for thrombotic events and normal prothrombin time, international normalized ratio (INR) and partial thromboplastin time

5. Women of child bearing potential have a negative serum pregnancy test prior to transplantation

6. Women of child bearing potential (including perimenopausal women who have had a menstrual period within the previous 1 year) who agree to use 2 forms of effective birth control regimen (at least one of which is a barrier method) throughout the study period and for 6 weeks following the end of the study or the last dose of mycophenolate mofetil, whichever comes first.

7. In the opinion of the investigator, the subject is capable of understanding and complying with the protocol.

8. Subjects must have signed the informed consent document prior to performance of any study related procedure including screening procedure.

Exclusion Criteria:

1. Recipient of multiple organ transplantation or scheduled for multiple organ transplantation
2. Recipient with a donor-specific anti-HLA antibody or positive cross-match requiring deviation from standard immunosuppressive therapy
3. Hepatitis C antibody positive, Hepatitis B antigen positive, or Hepatitis B core antibody positive
4. Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrollment into this study
5. Concurrent sepsis or active bacterial infection
6. In the opinion of the investigator is anatomically a high-risk renal transplant with higher chance for thrombosis or bleeding
7. Have an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been treated
8. Women of child bearing potential who are breastfeeding
9. History of HIV infection
10. Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.
11. Subject is not deemed medically stable for the study in the opinion of the Investigator or the subject's nephrologist.