Evaluation of Zr-89 Crefmirlimab PET Imaging for CD8+ T Cell Assessment in Renal Allograft Rejection

The primary objective is to characterize the distribution and intensity of the CD8+ T cell PET imaging signal derived from [89Zr]-Df‑Crefmirlimab in native and transplanted kidneys, cervical, hilar and mediastinal lymph nodes, spleen, liver, and bone marrow of kidney transplant recipients—including rejecting, non‑rejecting, and T‑cell depleted individuals—and in control subjects without renal disease, thereby evaluating feasibility for monitoring renal allograft rejection. The secondary objective is to assess the relationship between the PET signal in the transplanted kidney, spleen, bone marrow and lymph nodes and peripheral blood immune cell counts and phenotypic profiles in the same patients.

The study enrolled adult kidney transplant recipients aged 50–80 years, inclusive of both male and female participants. Candidates were selected from three predefined clinical categories: (1) recipients without suspicion of rejection, (2) recipients with biopsy‑proven or suspected rejection for which a biopsy was planned, and (3) recipients who had received T‑cell‑depleting antibodies within the preceding three months. All participants were required to provide written informed consent; female participants had to demonstrate post‑menopausal status or a negative pregnancy test combined with effective contraception. The sponsor did not provide information on the total number of participants enrolled. Lifestyle factors such as diet, physical activity, or smoking habits were not specified as selection criteria. The primary medical condition of interest was Renal allograft rejection.

The phase 3, category 2 study evaluates the feasibility of CD8⁺ T‑cell PET imaging using an intravenous dose of 44 MBq of renal allograft rejection‑targeted Zirconium‑89‑Df‑Crefmirlimab in kidney‑transplant recipients. Eligible participants are aged 50–80 years and belong to one of three cohorts: (1) transplant recipients without suspicion of rejection, (2) recipients with biopsy‑proven or suspected rejection, and (3) recipients who received T‑cell‑depleting antibodies within the preceding three months; all must provide written informed consent. The study schedule comprises a screening visit to confirm eligibility, a baseline PET/CT imaging visit performed within 7 days of screening, a follow‑up blood‑draw visit for flow‑cytometry assessment of immune subsets, and an end‑of‑study visit to conclude imaging and safety assessments. Participant involvement spans approximately 2–3 weeks from screening to final visit. Early termination may occur if a participant experiences a serious adverse reaction to the investigational product, withdraws consent, becomes pregnant, or fails to meet protocol‑defined safety criteria. Recruitment is planned from July 2026 to July 2027.

The investigational agent is identified as Zr89, supplied as an aqueous solution for intravenous (IV) administration. Each dose consists of 44 MBq (megabecquerel) of zirconium‑89‑labeled Crefmirlimab Berdoxam, delivered as a single infusion via the intravenous route.

No placebo or active comparator is incorporated in the protocol; participants continue to receive any standard‑of‑care therapies required for kidney transplantation management, which are not altered by the study procedures.

Administration of the imaging agent occurs on a predefined study day, with the infusion completed under clinical supervision. Following dosing, participants undergo scheduled PET scans to assess tracer distribution in native and graft kidneys, lymph nodes, spleen, liver, and bone marrow. Compliance with the imaging schedule is monitored through documented infusion records and verification of scan completion according to the study timeline.

Efficacy will be evaluated primarily by quantifying the PET signal of [⁸⁹Zr]-Df‑Crefmirlimab in the kidneys (native and graft), cervical, hilar and mediastinal lymph nodes, spleen, liver, and bone marrow using PET/CT imaging. The signal intensity will be compared between participants with renal allograft rejection, those without rejection, and those receiving T‑cell‑depleting therapy.

Secondary efficacy assessment will involve measurement of CD8⁺ T‑cell frequencies in peripheral blood by flow cytometry. Immune cell subsets will be quantified to complement the imaging findings and provide additional insight into the immunologic status of the transplant recipients.