Frexalimab Versus Tacrolimus for Prevention of Kidney Graft Rejection in Adult Kidney Transplant Recipients

The primary objective is to demonstrate the noninferiority of frexalimab compared to tacrolimus in preventing kidney transplant rejection. This evaluation is clinically significant for establishing the efficacy of the investigational treatment in maintaining graft integrity in adult kidney transplant recipients.

The secondary objectives include:

• Assessment of kidney graft function and the prevention of chronic allograft nephropathy.
• Evaluation of participant survival and graft survival.
• Analysis of the anti-graft response.
• Assessment of safety, tolerability, and immunogenicity.
• Characterization of pharmacokinetics for subcutaneous and intravenous administration.
• Evaluation of the on-body delivery system (OBDS) safety and patient reported outcomes (PRO) regarding tolerability.
• Monitoring the occurrence and control of comorbidities.

This clinical trial involves a total of 343 patients. The study population consists of both male and female individuals, including vulnerable populations. The participants are within the age ranges corresponding to codes 3 and 4. The primary medical condition under investigation is kidney transplant rejection. Included individuals are those scheduled to receive their first kidney transplant from either a living or deceased donor. The cohort is further characterized by having low to moderate immunological risk. The main objective is to demonstrate the noninferiority of frexalimab compared to tacrolimus in the prevention of graft rejection.

This Phase 2/3, seamless, randomized, open-label study is designed to evaluate the efficacy and safety of frexalimab compared to tacrolimus in adult recipients of a first kidney transplant. The primary objective is to demonstrate the noninferiority of frexalimab in preventing kidney transplant rejection. The study includes participants with low to moderate immunological risk. The primary efficacy endpoint is a composite efficacy failure rate, which includes biopsy-proven acute rejection, graft loss, and death, assessed at 1 year post-transplantation. Secondary endpoints include estimated glomerular filtration rate (eGFR) measurements, proteinuria, and various survival metrics collected at multiple intervals over a 5-year period. Study involvement includes a screening phase, followed by longitudinal monitoring at various follow-up visits to assess safety and efficacy. The total duration of the trial is estimated to extend from March 2026 to August 2033. Specific conditions leading to early termination or discontinuation of the study intervention are not explicitly detailed in the provided source data.

Frexalimab is the investigational medicinal product administered as a solution for injection. The route of administration includes intravenous, subcutaneous, or intramuscular delivery. The specific dosage for this substance is not defined in the provided data.

Tacrolimus is utilized as a comparator treatment. This substance is provided in the form of hard capsules for oral administration. The available strengths include 0.5 mg, 1 mg, and 5 mg. The administration frequency is documented as 12 units of dose.

The primary efficacy endpoint is the composite efficacy failure rate, which includes biopsy-proven acute rejection (BPAR), graft loss, and death, assessed at 1 year post kidney transplantation. Secondary efficacy assessments include the estimated glomerular filtration rate (eGFR) at multiple timepoints, specifically at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post transplantation. The change in eGFR from month 3 over time is also evaluated, alongside the status of eGFR levels relative to specific clinical thresholds at designated intervals.

Additional efficacy parameters include:

• Proteinuria levels at 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years post transplantation.
• The iBox score at 1 year post transplantation.
• Composite measures of participant and graft survival at 5 years, as well as survival over time at 6 months, 1 year, 2 years, 3 years, and 4 years.
• Death-censored graft survival and participant survival over time, including specific causes of graft loss and death.
• The yearly and cumulative incidence of BPAR, time to first BPAR, and the incidence of rejection episodes with clinical resolution up to 5 years.
• The incidence of de novo donor-specific antibodies at 1 year and 5 years post transplantation.
• Side effects of immunosuppressive therapy as evaluated by the MTSOSD-59R score at months 1, 2, 3, 4, 5, 6, and every 6 months thereafter.
• The incidence of new-onset diabetes post kidney transplantation.
• The incidence and prevalence of hypertension and dyslipidemia, including associated medication regimens and specific laboratory measures such as serum TG and various cholesterol levels.
• Frexalimab plasma concentration and the incidence, titer, and persistence of anti-drug antibodies (ADA).