Ensayos clínicos

Inclusion Criteria:

• Written informed consent must be obtained, from recipients and donors, before any assessment is performed on the respective subject.
• Recipient age ≥ 18 years.
• Donor age ≥ 18 and ≤ 60 years.
• Recipients of a first kidney transplant from a living unrelated or non-HLA identical living related donor.
• Donor willing to undergo mobilization, apheresis and 12-month safety follow-up and meets all local standard eligibility criteria to donate stem cells for allogeneic transplantation.
• Donor and Recipient: COVID-19 nucleic acid test (NAT) (e.g., SARS-CoV-2 RT-PCR) negative.
• Must be willing and able to comply with protocol-required visit schedule and visit requirements.

Exclusion Criteria - Recipient and Donor:

• Recipient or donor with use of other investigational drugs within 30 days (or within 5 drug half-lives) of signing informed consent.
• Recipient or donor with history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
• Recipient and donor who are identical twins.
• Recipient or donor who is a pregnant or nursing (lactating) woman.
• Recipient or donor with history of malignancy or premalignant syndrome (e.g., myelodysplastic syndrome) 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.

Exclusion Criteria - Recipient only:

• Multi-organ or cell transplant recipient.
• Panel reactive antibodies (calculated panel reactive antibody > 20% by Flow/Luminex).
• Recipient is blood type ABO incompatible or has positive crossmatch (Flow/Luminex) vs. donor.
• Presence of donor-specific antibodies (DSA) at any time pre-transplant.
• Recipient who is human immunodeficiency virus (HIV) hepatitis B surface antigen (HBsAg) or hepatitis c virus (HCV) positive. Recipients with history of HCV infection may participate if there is a documented history of treatment with an antiHCV agent and either one (1) negative polymerase chain reaction (PCR) at least three (3) months after last dose of treatment, or two (2) negative PCRs at least 2 weeks apart over a maximum of 4 weeks.
• Recipient with systemic infection, current or within the 2 weeks prior to conditioning; or history of recurrent infection (e.g., polycystic liver/kidney disease, unless native kidneys removed at time of transplant).
• Recipient with any baseline condition requiring or anticipated will require chronic or intermittent use of systemic steroids or other IS (e.g., autoimmune disease, asthma) throughout the course of the study.
• Recipient who had a live attenuated vaccine administered within 2 months of planned transplant surgery.
• Recipient with a body mass index (BMI) < 18 or > 35 kg/m^2 .
• Recipient requiring systemic anticoagulation; e.g., for hyper-coagulation disorders, deep vein thrombosis, atrial fibrillation, that cannot be temporarily interrupted which would preclude renal biopsy.
• Recipient with contraindication to total body irradiation (TBI) according to local radiologist; e.g., previous radiation therapy at a dose which would preclude TBI, inadequate pulmonary function.
• Recipient with autologous or allogeneic hematopoietic progenitor cell transplant prior to signing informed consent.
• All recipient women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, who do not agree to using highly effective methods of contraception during dosing of study treatment. For FCR-R WOCBP who have completely discontinued mycophenolate, contraception may be discontinued after Month 36 provided no mycophenolate is restarted. WOCBP assigned as FCR-D must maintain highly effective contraception from the time of assignment to FCR001 through 1 month after the end of the mobilization period. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e,g,, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) total hysterectomy or tubal ligation at least 6 weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject;
  • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
• In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before entering study screening.
• Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to study screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she considered not of childbearing potential.
• Sexually active male CTR-R must use a condom during intercourse throughout the study and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of drugs via seminal fluid. For FCR-R this requirement may be lifted at 6 weeks after MMF and tacrolimus have been discontinued.

Donor-only Exclusion Criteria:

• Multi-organ or cell transplant recipient.
• Panel reactive antibodies (calculated panel reactive antibody > 20% by Flow/Luminex).
• Recipient is blood type ABO incompatible or has positive crossmatch (Flow/Luminex) vs. donor.
• Presence of donor-specific antibodies (DSA) (positive result) at any time pretransplant.
• Recipient who is human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) positive. Recipients with history of HCV infection may participate if there is a documented history of treatment with an anti-HCV agent and have either one (1) documented negative polymerase chain reaction (PCR) at least three (3) months after last dose of treatment, or two (2) documented negative PCRs at least 2 weeks apart over a maximum of 4 weeks.
• Recipient with systemic infection, current or within the 2 weeks prior to conditioning; or history of recurrent infection (e.g., polycystic liver/kidney disease, unless native kidneys removed at time of transplant).
• Recipient with any baseline condition requiring or anticipated will require chronic or intermittent use of systemic steroids or other IS (e.g., autoimmune disease, asthma) throughout the course of the study.
• Recipient who had a live attenuated vaccine administered within 2 months of planned transplant surgery.
• Recipient with a body mass index (BMI) < 18 or > 35 kg/m^2.
• Recipient requiring systemic anticoagulation (e.g., for hyper-coagulation disorders, deep vein thrombosis, atrial fibrillation) that cannot be temporarily interrupted which would preclude renal biopsy.
• Recipient with contraindication to total body irradiation (TBI) according to local radiologist; e.g., previous radiation therapy at a dose which would preclude TBI, inadequate pulmonary function.
• Recipient with autologous or allogeneic hematopoietic progenitor or mesenchymal stem cell transplant prior to signing informed consent.
• All recipient women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, who do not agree to using highly effective methods of contraception during dosing of study treatment. For FCR-R WOCBP who have completely discontinued mycophenolate, contraception may be discontinued after Month 36 provided no mycophenolate is restarted. WOCBP assigned as FCR-D must maintain highly effective contraception from the time of assignment to FCR001 through 1 month after the end of the mobilization period. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception;
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment;
  • Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject;
  • Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before entering study screening. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to study screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment if she is considered not of childbearing potential.
• Sexually active male CTR-R must use a condom during intercourse throughout the study and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of drugs via seminal fluid. For FCR-R this requirement may be lifted at 6 weeks after MMF and tacrolimus have been discontinued.

Exclusion Criteria - Donor only:

• Biologically unrelated female donor transplant to male recipient.
• 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:
  • Medical diagnosis of ZIKV in the past 6 months;
  • Residence in, or travel to, an area with an increased risk for ZIKV transmission within the past 6 months;
  • Sex within the past 6 months with a person who has either of the risk factors listed in items (a) or (b), above.

Eligibility last updated10/4/21. Questions regarding updates should be directed to the study team contact.