Kidney transplant rejection Kidney transplant
Conditions
Interventions
Participants receive either frexalimab or tacrolimus. The treatment is chosen randomly for each participant, meaning it is determined by a computer program. This works like flipping a coin. Other medi
Sponsors
Sanofi-aventis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: I 01. Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place if >18 years) to 70 years of age inclusive at the time of signing the informed consent. I 02. Participants who are scheduled to receive their first kidney transplant from a living or deceased donor. In Part A in the US and EU, only deceased-donor recipients will be enrolled at the beginning; living-donor recipients may be enrolled later as stated in Section 4.1. I 03. Participants with low to moderate immunological risk, as defined by all the following criteria: • Current and historical calculated or virtual PRA <80%, AND • Current and historical negative donor HLA antibodies (DSA) per local practice, AND • ABO blood type compatible with the donor. "Current" indicates, in the absence of sensitizing events (eg, pregnancy, blood transfusion), the latest sample within 3 months prior to the screening visit; “Historical” refers to any available data. I 04. Male or female Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 12 weeks: • Refrain from donating or cryopreserving sperm PLUS, either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR-Must agree to use contraception as detailed below - A male condom and an additional highly effective contraceptive method as described in Section 10.4 when having sexual intercourse with a WOCBP who is not currently pregnant b. Female participants: • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a WONCBP as defined in Section 10.4 OR - Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), as described in Section 10.4 during the study intervention period (to be effective before starting the intervention) and for at least 26 weeks after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period. • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first administration of study intervention, see Section 8.3.5. - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. I 05. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion criteria
Exclusion criteria: E 01. Deceased donor kidney graft meets any of the following: 1. Donor >60 years old 2. Deceased donor >50 years old with at least 2 of the situations below: a. Death due to stroke b. History of hypertension c. Terminal creatinine >1.5 mg/dL 3. An anticipated cold ischemia time (CIT) >24 hours 4. Donation after cardiac (circulatory) death.E 02. Positive T or B cell crossmatch, or positive virtual crossmatch per local practice at screening. E 03. Participants receiving a kidney graft from HLA-identical living-related donors. E 04. Symptomatic herpes zoster within 3 months prior to screening. E 05. Evidence of active or latent TB as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and TB testing: either a positive TST (defined as a skin induration =5 mm at 48 to 72 hours, regardless of BCG or other vaccination history) or a positive (not indeterminate) TB test such as QuantiFERON®-TB Gold Plus test. NOTE: The choice to perform a TST or a QuantiFERON-TB Gold Plus test will be made by the Investigator according to local licensing and standard of care. The QuantiFERON-TB Gold Plus test can only be used in countries where it is licensed, and the use of this test is dependent on previous treatment(s). This test may not be suitable if previous treatment(s) produced significant immunosuppression. E 06. Participants whose primary causes of ESKD are primary (idiopathic) FSGS, C3 glomerulopathy (including C3 glomerulonephritis and dense deposit disease), lupus nephritis, or thrombotic microangiopathy (including atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura). Genetic FSGS is permitted. E 07. Participants who have known genetically predisposed thrombophilia, have history of thromboembolic events (including stroke and myocardial infarction), or who need long-term anti-coagulation therapy. Participants with prior thrombosis in dialysis access (including arteriovenous fistula, arteriovenous graft, or dialysis catheter) are permitted. The following conditions are permitted at Investigator’s discretion: Participants who had a myocardial infarction or transient ischemic attack more than 1 year before screening and are medically stable, participants taking antiplatelet for primary prevention of cardiac or cerebrovascular events, for stable coronary artery disease, or for stable thrombotic cerebrovascular events. E 08. Participants seronegative for EBV or with unknown EBV status. E 09. Participants with previous solid organ or cell transplant; recipient of a multiorgan transplant, or anticipated to receive a second solid organ or cell transplant in the next 5 years. Immediate post-transplant removal of previous kidney due to surgical complication is permitted. E 10. Participants receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant. E 11. Participants receiving paired kidneys (dual or en bloc kidney transplants). E 12. Participants who have severe medical co-morbidities, active infection, or severely limited life expectancy due to underlying medical conditions that are generally precluded from kidney transplant.E 13. Participants with any malignancy prior to screening (except for effectively treated carcinoma in situ of the cervix or adequately treated non metastatic squamous or basal cell carcinoma of the skin). E 14. Participants with a histor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite efficacy failure rate (BPAR, graft loss, and death) by 1 year post kidney transplantation. | — |
Secondary
| Measure | Time frame |
|---|---|
| eGFR at 1 year post kidney transplantation. Composite of participant and graft survival at 5 years post kidney transplantation. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Saudi Arabia, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactK. Wei
Sanofi-aventis
Outcome results
None listed