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A Safety and Efficacy Study of FCR001 vs Standard of Care in de Novo Living Donor Kidney Transplantation (FREEDOM-1)

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: NCT03995901
Recruitment Status : Recruiting
First Posted : June 24, 2019
Last Update Posted : July 27, 2022
Sponsor:
Information provided by (Responsible Party):
Talaris Therapeutics Inc.

Brief Summary:
A randomized controlled study to evaluate the safety, efficacy, and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation.

Condition or disease Intervention/treatment Phase
Transplanted Organ Rejection Biological: FCR001 Phase 3

Detailed Description:
The purpose of this randomized (2:1) controlled study is to evaluate the safety, efficacy and overall benefit of FCR001 cell therapy in first or second de novo living donor renal transplantation relative to a standard-of-care control immunosuppression regimen of antibody induction, tacrolimus, mycophenolate, and corticosteroids.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Multi-center, Safety and Efficacy Study of FCR001 Cell-based Therapy Relative to a Tacrolimus and Mycophenolate-based Regimen in de Novo Living Donor Renal Transplant Recipients, and Safety in FCR001 Donors
Actual Study Start Date : October 25, 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FCR001
FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood of the kidney donor that is delivered as a single dose with a non- myeloablative conditioning regimen. FCR001 contains the donor's CD34+ cells, facilitating cells, and αβ T cells.
Biological: FCR001
FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood of the kidney donor that is delivered as a single dose with a non- myeloablative conditioning regimen. FCR001 contains the donor's CD34+ cells, facilitating cells, and αβ T cells.
Other Names:
  • Cell based therapy
  • Allogeneic stem cell transplant

No Intervention: Control

Standard induction therapy followed by a maintenance regimen of tacrolimus, mycophenolate, and +/- corticosteroids after kidney transplant.

Control donors are not followed beyond randomization.




Primary Outcome Measures :
  1. Proportion of FCR001 recipients who are free from immunosuppression (IS), without biopsy proven acute rejection (BPAR) at 24 months post-transplant [ Time Frame: 24 months post-transplant ]

    Free from IS is defined as not taking any immunosuppression medications and not having to take immunosuppression medications since their withdrawal.

    Biopsy proven acute rejection is defined as Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).



Secondary Outcome Measures :
  1. Change in renal function by Modification of Diet in Renal Disease (MDRD4) from post-transplant baseline (Month 1) to Month 24 in FCR001 recipients [ Time Frame: 24 months post-transplant ]
  2. Proportion of FCR001 recipients free from IS, without BPAR, at Month 36 and 60 [ Time Frame: Month 36 and 60 post transplant ]
  3. Allograft function (eGFR by MDRD4) and change in eGFR from Month 1 to Month 24, 36, and Month 60, by treatment [ Time Frame: Month 1 (post-transplant) to Month 24, 36, and Month 60 ]
  4. Slope and difference in slope of estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD4) over time to Month 24, 36, and 60, by treatment [ Time Frame: Month 24, 36, and 60 ]
  5. Allograft function (eGFR) and change in renal allograft function from Month 1 to Months 24, 36 and 60 by treatment group, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula [ Time Frame: Month 1 (post transplant) to Month 24, 36, and Month 60 ]
  6. Time to the event for the composite of BPAR, graft loss, death or lost to follow-up and for each component, by treatment group [ Time Frame: Month 1 (post transplant) to Month 6, 12, 24, 36, and 60 ]
  7. Incidence of composite endpoint of BPAR, graft loss or death, by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  8. Incidence of composite endpoint of BPAR, graft loss, or death and lost to follow-up, by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  9. Incidence of BPAR and treated BPAR by severity, type, and steroid-resistance, by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  10. Incidence of acute rejection [ Time Frame: Months 12, 24, 36 and 60 ]
  11. Incidence of de novo donor-specific antibodies [ Time Frame: Months 12, 24, 36 and 60 ]
  12. Incidence or worsening of abnormal histologic findings of cellular or antibody-mediated chronic rejection, chronic glomerulopathy, tubular atrophy and interstitial fibrosis, C4d, calcineurin inhibitor induced damage, disease recurrence, BK nephropathy [ Time Frame: Months 12, 24, 36 and 60 ]
  13. Incidence of renal replacement therapy by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  14. Incidence of BPAR or eGFR <50 mL/min by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  15. Categorical distribution of eGFR according to chronic kidney disease CKD staging classification by treatment [ Time Frame: Months 12, 24, 36 and 60 ]
  16. Incidence and severity of adverse events (AEs; including infections), serious adverse events (SAEs) and AEs leading to study and/or regimen discontinuation [ Time Frame: Months 12, 24, 36 and 60 ]
  17. Incidence of BK viremia, viruria, infection, and nephropathy by treatment [ Time Frame: Months 12, 24, 36 and 60 ]
  18. Incidence of the adverse events of special interest (proteinuria, neurotoxicity, anemia, diabetes, hypertension, dyslipidemia, opportunistic infections, major adverse cardiovascular events, and malignancies [ Time Frame: Months 12, 24, 36 and 60 ]
  19. Urinary protein and albumin excretion, estimated by urinary protein/creatinine and urinary albumin/creatinine ratios by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  20. Subject quality of life according to 36-Item Short Form Health Survey (SF-36) will be analyzed descriptively by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  21. Subject quality of life according to End-Stage Renal Disease Symptom Checklist (ESRD-SCL) will be analyzed descriptively by treatment group [ Time Frame: Months 12, 24, 36 and 60 ]
  22. Incidence and duration of hospitalization and readmission, according to type of ward/unit [ Time Frame: Months 12, 24, 36 and 60 ]
  23. iBox predicted allograft survival [ Time Frame: Months 12 and 24 post-transplant ]
  24. Graft and patient survival and eGFR in FCR001 recipients who are only transiently chimeric [ Time Frame: Month 24, 36, and 60 ]
  25. To describe the incidence and severity of AEs (including infections) and SAEs among FCR001 donors [ Time Frame: Month 24, 36, and 60 ]
  26. Incidence of acute rejection, death, renal graft loss, and lost to follow-up between FCR001 recipients who did not achieve durable chimerism or the ability to wean or remain off immunosuppression vs. the control arm [ Time Frame: Month 24, 36, and 60 ]
  27. The incidence of autologous infusions in FCR001 recipients [ Time Frame: Month 6, 12, 24, 36, and 60 ]
  28. The incidence of engraftment syndrome in FCR001 recipients [ Time Frame: Month 6, 12, 24, 36, and 60 ]
  29. The incidence of blood component transfusions in FCR001 recipients [ Time Frame: Month 6, 12, 24, 36, and 60 ]
  30. The time to neutrophil and platelet recovery in FCR001 recipients [ Time Frame: Month 6, 12, 24, 36, and 60 ]
  31. The incidence of acute and chronic Graft versus Host Disease (GvHD) in FCR001 recipients will be described [ Time Frame: Month 6, 12, 24, 36, and 60 ]
  32. The incidence of donor chimerism and level of chimerism by study visit in FCR001 recipients will be described [ Time Frame: Month 6, 12, 24, 36, and 60 ]
  33. The correlation of donor chimerism with freedom from IS)in FCR001 recipients will be described [ Time Frame: Month 6, 12, 24, 36, and 60 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Recipient age ≥18 years.
  • Donor age ≥18 and ≤60 years at time of signing informed consent.
  • Recipients of a first or second living donor kidney transplant
  • Donor willing to undergo mobilization, apheresis and 12-month safety follow-up and meet all local standard eligibility criteria to donate stem cells for allogeneic transplantation.
  • Recipient meets all local standard eligibility criteria for allogeneic stem cell transplant.
  • Donors must be deemed eligible as per the requirements of 21CFR1271.

Main Recipient and Donor Exclusion Criteria:

  • Recipient and donor who are identical twins.
  • Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome, monoclonal gammopathy of renal significance [MGRS], monoclonal gammopathy of unknown significance [MGUS]) of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
  • Recipient or donor with known bone marrow aplasia.

Main Recipient-only Exclusion Criteria:

  • Multi-organ or stem cell transplant recipient.
  • Calculated panel reactive antibodies >80%.
  • Recipient is blood type ABO incompatible with donor.
  • Presence of donor-specific antibodies (DSA) (positive result) at any time pre-transplant.
  • Recipient who is human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) positive.
  • Recipient with any baseline condition requiring or anticipated will require chronic or intermittent use of systemic steroids or other IS (eg, autoimmune disease, asthma) throughout the course of the study.
  • Recipient with a BMI < 18 or > 35 kg/m2.
  • Recipient requiring systemic anticoagulation, (eg, for hyper-coagulation disorders, deep vein thrombosis, atrial fibrillation) that cannot be temporarily interrupted which would preclude renal biopsy.

Main Donor-only Exclusion Criteria:

  • Biologically unrelated (i.e., no genetic relationship) female donor transplant to male recipient.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03995901


Locations
Show Show 17 study locations
Sponsors and Collaborators
Talaris Therapeutics Inc.
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Responsible Party: Talaris Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03995901    
Other Study ID Numbers: FCR001A2301
First Posted: June 24, 2019    Key Record Dates
Last Update Posted: July 27, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Talaris Therapeutics Inc.:
Kidney Transplant
Stem cell therapy
Anti-rejection medications
Living donor kidney transplant
Immune tolerance
Immunosuppression
Immunosuppressive medication
Organ transplant rejection