siRNA (nucleic acid) — complex RNA oligonucleotide (as listed in product details) for Antibody-mediated rejection after kidney transplantation|Antibody-mediated rejection

Inclusion criteria

• {"criterion_text":"- ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.\n- To reduce the risk of meningococcal infection (N meningitidis), all participants 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. Participants who do not meet this requirement will be vaccinated against meningococcal infection before receiving the first dose of study intervention. If vaccination occurs < 14 days prior to Day 1, the participants will receive prophylactic antibiotics for at least 14 days after meningococcal vaccination for serogroups A, C, W, Y (and B where available). Participants must agree to get revaccinated according to national/local guidelines.\n- Must be vaccinated for S pneumoniae prior to randomization according to current national/local vaccination guidelines.\n- Must be vaccinated for H influenzae type B (where available) prior to randomization according to current national/local vaccination guidelines. If vaccination is not clinically indicated due to the inability to mount an immune response, see Section 8.3.9 of the Protocol for instructions on antibiotic prophylactics.\n- Kidney transplant received ≥6 months prior to Screening.\n- Diagnosis of active or chronic active AMR according to Banff 2022 classification based on Screening kidney biopsy\n- Biopsy-proven histologic score ≥ 2 (g ≥ 1 and ptc ≥ 1) at Screening\n- eGFR ≥ 30 mL/min/1.73 m2 at Screening\n- Body weight ≥ 50 kg at Screening.\n- Male or female assigned at birth, inclusive of all gender identities.\n- CBP participants and CBP participants partners must follow protocol-specified contraception guidance.\n- Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol."}

Exclusion criteria

• {"criterion_text":"- Biopsy-based diagnosis of any of the following at Screening: • TCMR, according to the Banff grade ≥ 1 (note: participants with borderline TCMR are eligible for the study) • Polyoma virus nephropathy • Severe thrombotic microangiopathy • Glomerulonephritis\n- Known medical or psychological conditions, including substance use disorder (including alcohol), or risk factor that, in the opinion of the Investigator, might interfere with the participant’s full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.\n- Hypersensitivity to any ingredient contained in the study intervention, including history of hypersensitivity to an oligonucleotide or GalNAc moiety.\n- Any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.\n- 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, interleukin inhibitors, proteasome inhibitors, high-dose corticosteroids [except for tapering]), HDS products with known hepatotoxic ingredients, TCMR (including T-cell depleting therapy), excluding the SoC treatment which will be allowed and should be stable during the entire treatment. The participant not on an immunosuppressive regimen containing a calcineurin inhibitor must be excluded.\n- Participation in another interventional treatment study or use of any experimental therapy within 90 days prior to Screening or within 5 half-lives of that investigational product, whichever is greater, or planned participation/use during the course of the study.\n- Pregnant, breastfeeding, or intending to conceive within 6 months after the last dose of study intervention.\n- Alanine transaminase (ALT) or aspartate transaminase (AST) > 2 × ULN or ratio AST/ALT > 0.8 when ALT or AST is abnormal (abnormal ALT or AST can be retested if between ULN and 2 × ULN).\n- Total bilirubin > 2 × ULN (participants with Gilbert’s syndrome can be included with total bilirubin > 2 × ULN as long as direct bilirubin is ≤ 1.5 × ULN).\n- Known current acute or active chronic liver disease eg. cirrhosis, MASH, fatty liver, and alcoholic hepatitis.\n- ABO-incompatible transplant\n- Any of the following abnormal laboratory results at Screening: • uACR > 2200 mg/g indicating nephrotic range proteinuria • Hemoglobin < 8 g/dL • Platelets < 100 × 109/L • Leucocytes < 3 × 109/L • Neutrophils < 1.5 × 109/L\n- Multi-organ transplant recipient (except for simultaneous kidney-pancreas or previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient.\n- Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.\n- Participants with history of HIV who are not on anti-retroviral therapy or if on therapy have a known detectable viral load within 1 year of Screening.\n- Evidence of hepatitis B or hepatitis C infections according to the following criteria at Screening: • Testing positive for HBsAg, OR • Testing positive for HBcAb while having a negative HBsAb HBsAband HBV DNA by reflex testing detected above the LLOQ by the local or central laboratory at Screening. • Positive hepatitis C antibody test result at Screening or within 3 months unless HCV RNA negative test by local or central laboratory is documented.\n- Congenital immunodeficiency.\n- History of unexplained, recurrent infection."}

Primary endpoints

• {"endpoint_text":"- Biopsy-proven histologic resolution at Week 52","definition_or_measurement_approach":"Biopsy-proven histologic resolution assessed by kidney biopsy at Week 52 (biopsy-proven histologic resolution at Week 52)."}

Secondary endpoints

• {"endpoint_text":"- Biopsy-proven histologic resolution at Week 28.","definition_or_measurement_approach":"Biopsy-proven histologic resolution assessed by kidney biopsy at Week 28."}
• {"endpoint_text":"- Resolution of AMR activity at Weeks 28 and 52.","definition_or_measurement_approach":"Assessment of resolution of antibody-mediated rejection activity at Weeks 28 and 52."}
• {"endpoint_text":"- Change from baseline in biopsy-proven histologic score at Weeks 28 and 52.","definition_or_measurement_approach":"Change from baseline in histologic score measured by biopsy at Weeks 28 and 52."}
• {"endpoint_text":"- eGFR change from baseline at Week 52.","definition_or_measurement_approach":"Change from baseline in estimated glomerular filtration rate (eGFR) measured at Week 52."}
• {"endpoint_text":"- Annualized total eGFR slope during 52 weeks of treatment.","definition_or_measurement_approach":"Annualized total eGFR slope calculated over 52 weeks of treatment."}
• {"endpoint_text":"- Stabilized eGFR (annualized eGFR slope > -1) during 52 weeks of treatment.","definition_or_measurement_approach":"Proportion or assessment of participants with annualized eGFR slope > -1 over 52 weeks."}
• {"endpoint_text":"- Incidence of TEAEs and TESAEs over time.","definition_or_measurement_approach":"Recording and reporting of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) across study visits."}
• {"endpoint_text":"- ALXN2030 plasma concentration over time.","definition_or_measurement_approach":"Pharmacokinetic measurement of ALXN2030 plasma concentrations over time."}
• {"endpoint_text":"- Absolute values, change from Baseline and percent change from Baseline in plasma concentrations of C3 protein over time and in serum complement functional activity over time.","definition_or_measurement_approach":"Measurement of plasma C3 protein concentrations and serum complement functional activity: absolute, change from baseline, and percent change over time."}
• {"endpoint_text":"- Anti-ALXN2030 Ab incidence, category of ADA response, and titer through the duration of the study.","definition_or_measurement_approach":"Assessment of anti-ALXN2030 antibody incidence, ADA response category, and titers throughout the study."}

Spain

Earliest CTIS Part Ii Submission Date

26-09-2025

Latest Decision Or Authorization Date

11-03-2026

Processing Time Days

166

Number Of Sites

3

Number Of Participants

6

Primary sponsor

Full Name

Alexion Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States