Condition or disease | Intervention/treatment | Phase |
---|---|---|
Transplanted Organ Rejection | Biological: FCR001 | Phase 3 |
The purpose of this randomized (2:1) controlled study is to assess the safety, efficacy and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation relative to a standard-of-care control immunosuppression regimen of antibody induction, tacrolimus, mycophenolate, and corticosteroids.
FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood of the kidney donor that is delivered as a single dose in kidney transplant recipients who received a non-myeloablative conditioning regimen. FCR001 contains the donor's CD34+ cells, facilitating cells, and αβ T cells. This therapy induces or restores patients' immune tolerance by establishing stable donor chimerism in the transplant recipient without the need for life-long immunosuppression.
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 |
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:
|
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. |
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 Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
Renal function is evaluated by estimated glomerular filtration rate (eGFR) calculated using the MDRD4 formula (Coresh et al. 2003).
Modification of Diet in Renal Disease (MDRD) formula is:
GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where C is the serum concentration of creatinine [mg/dL], A is patient age at sample collection date [years], G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1.
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).
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).
Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.
Loss to follow-up is a subject whose status is unclear because he/she fails to appear for study visits without stating an intention to withdraw and did not respond to repeated attempts of contact, who did not experience graft loss or death from Day 1 and whose last day of contact was prior to study Month 60.
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).
Graft loss is defined by 56 consecutive days of hemodialysis or re-transplantation.
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).
Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.
Loss to follow-up is a subject whose status is unclear because he/she fails to appear for study visits without stating an intention to withdraw and did not respond to repeated attempts of contact, who did not experience graft loss or death from Day 1 and whose last day of contact was prior to study Month 60.
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).
Treated BPAR are those BPARs treated with antirejection medications. BPAR and treated BPAR will be characterized by severity, type and steroid resistance.
BPAR Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
Estimated glomerular filtration rate (eGFR) is calculated using the MDRD4 formula (Coresh et al. 2003).
An Adverse Event (AE) is any untoward medical occurrence (ie, any unfavorable and unintended sign, symptom or disease).
A Serious Adverse Event is defined as any AE (appearance of or worsening of any pre-existing undesirable sign, symptom or medical conditions) which meets any one of the following criteria: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, or is medically significant
Graft loss and death are used to determine graft survival and patient survival respectively. Both will be evaluated in FCR001 recipients who achieve a donor chimerism of >50% donor T-cells measured in recipient blood but then falls below 50% T-cells.
Graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.
An Adverse Event is any untoward medical occurrence (ie, any unfavorable and unintended sign, symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study.
A Serious Adverse Event is defined as any AE (appearance of or worsening of any pre-existing undesirable sign, symptom or medical conditions) which meets any one of the following criteria: is fatal or life-threatening, results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, requires inpatient hospitalization or prolongation of existing hospitalization, or is medically significant.
Adverse events and Serious Adverse Events for FCR001 donors will be summarized.
In this composite endpoint, acute rejection is defined as a BPAR Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
Renal graft loss is defined as 56 consecutive days of hemodialysis or re-transplantation.
Loss to follow-up is a subject whose status is unclear because he/she fails to appear for study visits without stating an intention to withdraw and did not respond to repeated attempts of contact, who did not experience graft loss or death from Day 1 and whose last day of contact was prior to study Month 60.
Durable chimerism is defined as maintaining at least 50% donor T-cells measured in recipient blood.
For FCR recipients, inability to wean immunosuppression is defined as not meeting the criteria (BPAR >1A, chimerism <50% T-cells of donor, no graft versus host disease and having stable renal function) to discontinue their antirejection medications. Inability to remain
Freedom from immunosuppression is defined as the ability to discontinue anti-rejection medications and not having to restart any antirejection medication.
Donor chimerism is defined by > 50% donor T-cells measured in recipient blood.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Recipient and Donor Exclusion Criteria:
Recipient-only Exclusion Criteria:
Donor-only Exclusion Criteria:
Donor tested positive for Zika virus (ZIKV) infection. Zika infection is excluded by negative nucleic acid testing result on either serum or urine PLUS a negative Zika IgM. Only donors with the following risk factors must be tested:
United States, Arizona | |
Mayo Clinic | Recruiting |
Phoenix, Arizona, United States, 85054 | |
Contact: Leena Abraham, RN 480-342-6750 Abraham.leena@mayo.edu | |
United States, California | |
Scripps Clinic | Recruiting |
La Jolla, California, United States, 92037 | |
Contact: Michelle Meyer 858-554-4340 Meyer.Michelle@scrippshealth.org | |
United States, District of Columbia | |
Georgetown University Hospital | Recruiting |
Washington, District of Columbia, United States, 20007 | |
Contact: Alyssa Stucke, BS, CCRC 202-444-1769 Alyssa.E.Stucke@gunet.georgetown.edu | |
United States, Illinois | |
Northwestern Memorial Hospital | Recruiting |
Chicago, Illinois, United States, 60611 | |
Contact: Dianne Belshe, RN 312-694-0240 dianne.stare@northwestern.edu | |
United States, Minnesota | |
University of Minnesota Medical Center | Recruiting |
Minneapolis, Minnesota, United States, 55455 | |
Contact: Dave Ankarlo 612-626-2498 anka0004@umn.edu | |
Mayo Clinic | Recruiting |
Rochester, Minnesota, United States, 55905 | |
Contact: Nong Yowe Braaten 507-538-9617 braaten.nong@mayo.edu | |
United States, Nebraska | |
University of Nebraska Medical Center | Recruiting |
Omaha, Nebraska, United States, 68198 | |
Contact: Cliff Miles, MD 402-559-4719 cdmiles@unmc.edu | |
United States, New York | |
New York-Presbyterian/Weill Cornell | Not yet recruiting |
New York, New York, United States, 10065 | |
Contact: Sandip Kapur, MD | |
United States, North Carolina | |
Duke University Medical Center | Recruiting |
Durham, North Carolina, United States, 27710 | |
Contact: Sherri Swan-Nesbit 919-613-6472 sherri.swan@duke.edu | |
United States, Ohio | |
The Ohio State University Wexner Medical Center | Recruiting |
Columbus, Ohio, United States, 43210 | |
Contact: Corey Newsome 614-293-5648 corey.newsome@osumc.edu | |
United States, Oregon | |
Oregon Health & Science University | Recruiting |
Portland, Oregon, United States, 97239 | |
Contact: Liz Veasey 503-494-2884 veaseye@ohsu.edu |
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date ICMJE | June 13, 2019 | ||||
First Posted Date ICMJE | June 24, 2019 | ||||
Last Update Posted Date | February 24, 2021 | ||||
Actual Study Start Date ICMJE | October 25, 2019 | ||||
Estimated Primary Completion Date | April 2023 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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 Grade ≥1A according to the Banff 2017 Classification of Antibody-Medicated Rejection and T Cell-Mediated Rejection in Renal Allografts (Haas et al 2018).
|
||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
|
||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | A Safety and Efficacy Study of FCR001 vs Standard of Care in de Novo Living Donor Kidney Transplantation | ||||
Official Title ICMJE | 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 | ||||
Brief Summary | A randomized controlled study to assess the safety and efficacy and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation. | ||||
Detailed Description |
The purpose of this randomized (2:1) controlled study is to assess the safety, efficacy and overall benefit of FCR001 cell therapy in de novo living donor renal transplantation relative to a standard-of-care control immunosuppression regimen of antibody induction, tacrolimus, mycophenolate, and corticosteroids. FCR001 is a cryopreserved allogeneic stem cell therapy derived from mobilized peripheral blood of the kidney donor that is delivered as a single dose in kidney transplant recipients who received a non-myeloablative conditioning regimen. FCR001 contains the donor's CD34+ cells, facilitating cells, and αβ T cells. This therapy induces or restores patients' immune tolerance by establishing stable donor chimerism in the transplant recipient without the need for life-long immunosuppression. |
||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 3 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||
Condition ICMJE | Transplanted Organ Rejection | ||||
Intervention ICMJE | 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:
|
||||
Study Arms ICMJE |
|
||||
Publications * |
|
||||
* 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 |
240 | ||||
Original Estimated Enrollment ICMJE |
120 | ||||
Estimated Study Completion Date ICMJE | April 2025 | ||||
Estimated Primary Completion Date | April 2023 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Recipient and Donor Exclusion Criteria:
Recipient-only Exclusion Criteria:
Donor-only Exclusion Criteria:
|
||||
Sex/Gender ICMJE |
|
||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | |||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03995901 | ||||
Other Study ID Numbers ICMJE | FCR001A2301 | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
|
||||
IPD Sharing Statement ICMJE |
|
||||
Responsible Party | Talaris Therapeutics Inc. | ||||
Study Sponsor ICMJE | Talaris Therapeutics Inc. | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE | Not Provided | ||||
PRS Account | Talaris Therapeutics Inc. | ||||
Verification Date | February 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |