The primary objective of this study is to evaluate the efficacy of ALXN2030 compared with placebo on biopsy proven histologic resolution in participants with active or chronic active antibody-mediated rejection (AMR) at Week 52.

This prospective trial will assess the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN2030 in kidney transplant recipients with active or chronic active AMR. The study is designed as a randomized, controlled, double-blind phase 2 trial. Participants will be randomized in a 1:1:1 ratio to receive either ALXN2030 Dose A, ALXN2030 Dose B, or placebo for a double-blind treatment period of 52 weeks. All arms will receive standard of care immunosuppressive treatment. During the treatment period, study participants will be subjected to repeated allograft biopsies at 28 and 52 weeks. At the end of the double-blind treatment period, participants may continue into the Open-Label Extension (OLE) Treatment Period (52 weeks). Participants randomized to placebo will be re-randomized 1:1 to ALXN2030 Dose A or ALXN2030 Dose B. Safety Follow-Up will start after the end of Treatment (Week 104) until week 48 after the last dose.

Inclusion Criteria:

• Kidney transplant received ≥ 6 months
• Active or chronic active AMR according to Banff 2022 classification, based on Screening kidney biopsy
• Either positive C4d on Screening kidney biopsy based on the Central Pathology Laboratory report and/or positive HLA Class I and/or II antigen-specific DSA as determined by the local laboratory's definition of positivity using single-antigen bead based assays
• MVI score ≥ 2 (g ≥ 1 and ptc ≥ 1)
• eGFR ≥ 30 mL/min/1.73 m2
• Must be vaccinated against meningococcal infection from serogroups A, C, W, Y (and B where available) at least 14 days prior to but no more than 3 years prior to Day 1
• Must be vaccinated for S pneumoniae prior to randomization
• Must be vaccinated for H influenzae type B (where available) prior to randomization
• Body weight ≥ 50 kg at Screening

Exclusion Criteria:

• Biopsy-based diagnosis of any of the following at Screening:
• TCMR, according to the Banff grade ≥ 1
• Polyoma virus nephropathy
• Severe thrombotic microangiopathy
• Glomerulonephritis
• ABO-incompatible transplant
• uACR > 2200 mg/g
• Multiorgan transplant recipient (except for previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient
• Planned or recent treatments, < 90 days prior to the Screening Visit and during Screening, for Acute Rejection, AMR (including plasmapheresis, plasma exchange, IVIg, B-cell depleting therapy, IL inhibitors, proteasome inhibitors, high-dose corticosteroids [except for tapering]), HDS products with known hepatotoxic ingredients, TCMR (including T-cell depleting therapy), excluding the SoC immunosuppressant treatment which will be allowed and should be stable during the entire treatment.
• Known medical or psychological condition, including substance abuse or use disorder (including alcohol), or risk factor that may interfere with study participation, pose additional risk, or confound study outcomes

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