Efficacy and Safety Evaluation of ALXN2030 in Antibody-Mediated Rejection Post-Kidney Transplantation: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study
- Trial ID
- 2024-517498-25-00
- Protocol
- ALXN2030-AMR-201
- Sponsor
- Alexion Pharmaceuticals Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the efficacy of ALXN2030 compared to a placebo regarding biopsy-proven histologic resolution in adult patients experiencing active or chronic active antibody-mediated rejection at week 52. 5
The secondary objectives include:
- Evaluation of histologic score and the resolution of rejection activity. 5
- Assessment of renal function through estimated glomerular filtration rate (eGFR), including eGFR stabilization and total eGFR slope. 5
- Assessment of safety and tolerability. 4
- Characterization of pharmacokinetics and pharmacodynamics. 6, 7, 9
- Evaluation of immunogenicity.
Participants
This study involves 44 participants diagnosed with antibody-mediated rejection following kidney transplantation. The study population includes both males and females, with ages ranging from 18 to 75 years. Eligible individuals must have received a kidney transplant at least 6 months prior to screening and present with a biopsy-proven histologic score of ≥ 2 based on the Banff 2022 classification. Additional requirements include an estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m2 and a body weight of at least 50 kg. Participants are required to have completed specific vaccinations against meningococcal infection, Streptococcus pneumoniae, and Haemophilus influenzae type B prior to randomization.
Plans and Procedures
This Phase 2, double-blind, randomized, placebo-controlled, multicenter study is designed to evaluate the efficacy and safety of ALXN2030 compared to a saline placebo in adults diagnosed with antibody-mediated rejection after kidney transplantation. The methodology focuses on assessing biopsy-proven histologic resolution as the primary endpoint at Week 52. Following a screening period to confirm eligibility based on specific histologic scores, renal function, and vaccination requirements, participants are randomized to receive either the study intervention or the placebo via intravenous, subcutaneous, or intramuscular routes. Study procedures include scheduled follow-up visits to monitor secondary endpoints, such as changes in estimated glomerular filtration rate (eGFR) and the incidence of treatment-emergent adverse events. The expected duration of participant involvement is 52 weeks. Early termination may occur based on protocol-specified conditions or clinical safety requirements.
Treatment
ALXN2030 is an experimental solution for injection administered at a dose of 450 mg. The route of administration includes intravenous, subcutaneous, or intramuscular injection. The active substance is a complex involving RNA and a specific nucleotide sequence modified with 2'-deoxy-2'-fluoro and N-acetylgalactosamine conjugates.
Vialed Saline Placebo is utilized as a placebo in this study. This non-experimental treatment is intended for comparison against the investigational product to evaluate efficacy and safety in patients with antibody-mediated rejection following kidney transplantation.
Efficacy
The efficacy of ALXN2030 is evaluated using biopsy-proven histologic resolution as the primary endpoint at Week 52. Secondary efficacy assessments include histologic resolution at Week 28 and the resolution of AMR activity at both Week 28 and Week 52. The study also measures the change from baseline in biopsy-proven histologic score at these timepoints.
Renal function is assessed through several parameters:
- eGFR change from baseline at Week 52.
- Annualized total eGFR slope during 52 weeks of treatment.
- Stabilized eGFR, defined as an annualized eGFR slope greater than -1, during the 52-week treatment period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
- Kidney transplant received ≥6 months prior to Screening.
- Diagnosis of active or chronic active AMR according to Banff 2022 classification based on Screening kidney biopsy
- Biopsy-proven histologic score ≥ 2 (g ≥ 1 and ptc ≥ 1) at Screening
- eGFR ≥ 30 mL/min/1.73 m2 at Screening
- Body weight ≥ 50 kg at Screening.
- Male or female assigned at birth, inclusive of all gender identities.
- CBP participants and CBP participants partners must follow protocol-specified contraception guidance.
- Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
- 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.
- Must be vaccinated for S pneumoniae prior to randomization according to current national/local vaccination guidelines.
- 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.
Exclusion Criteria
- 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
- ABO-incompatible transplant
- 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
- Multi-organ transplant recipient (except for simultaneous kidney-pancreas or previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient.
- Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.
- 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.
- 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.
- Congenital immunodeficiency.
- History of unexplained, recurrent infection.
- 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.
- Hypersensitivity to any ingredient contained in the study intervention, including history of hypersensitivity to an oligonucleotide or GalNAc moiety.
- 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.
- 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.
- 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.
- Pregnant, breastfeeding, or intending to conceive within 6 months after the last dose of study intervention.
- 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).
- 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).
- Known current acute or active chronic liver disease eg. cirrhosis, MASH, fatty liver, and alcoholic hepatitis.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Jan 2026 | 6 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Vialed Saline Placebo | Placebo | N/A | — | — | — | N/A |
ALXN2030 | Test | SOLUTION FOR INJECTION | INTRAVENOUS/SUBCUTANEOUS/INTRAMUSCULAR | 450 | 104 | PRD12108637 |