Phase 2 Study of ALXN2030 in Patients With Antibody-Mediated Rejection After Kidney Transplantation

Phase 2

Active, not recruiting

• Conditions: Antibody-Mediated Rejection; Kidney Transplantation; Biopsy-proven Histologic Scores; AMR
• Interventions: Drug: ALXN2030; Drug: Placebo

• Registration Number: NCT06744647
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

This prospective trial will assess the efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN2030 in kidney transplant recipients with late 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.

Study Timeline

• Study First Submitted: 2024-12-13
• Study First Submitted QC: 2024-12-18
• Study First Posted: 2024-12-20
• Study Start: 2025-03-07
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-23
• Primary Completion: 2027-04-06
• Study Completion: 2028-05-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Kidney transplant received ≥ 6 months
• Active or chronic active AMR according to Banff 2022 classification, based on Screening kidney biopsy
• HLA-DSA (preformed and/or de novo DSA)
• MVI score ≥ 2 (g ≥ 1 and ptc ≥ 1)
• eGFR ≥ 30 mL/min/1.73 m2
• Must be vaccinated for S pneumoniae prior to randomization
• Must be vaccinated for H influenzae type B (where available) prior to randomization

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 indicating nephrotic range proteinuria
• Hemoglobin < 8 g/dL
• Platelets < 100 × 109/L
• Leucocytes < 3 × 109/L
• Neutrophils < 1.5 × 109/L
• Multiorgan transplant recipient (except for 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
• Congenital immunodeficiency
• History of unexplained, recurrent infection
• Pregnant, breastfeeding, or intending to conceive within 6 months after the last dose of study intervention
• ALT or AST > 2.0 × 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)
• Current or chronic history of liver disease that is considered clinically significant by the Investigator
• Planned or recent treatments, < 3 months prior to the Screening Visit, for Acute Rejection, AMR (including plasmapheresis, plasma exchange, IVIg, B-cell depleting therapy, IL inhibitors, proteasome inhibitors, high-dose corticosteroids [except for tapering]), TCMR (including T-cell depleting therapy), excluding the SoC treatment which will be allowed and should be stable during the entire treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALXN2030 Dose A	ALXN2030	During the Double-Blind Treatment Period, participants will receive ALXN2030 dose A over 52 weeks. At Week 52, participants may continue into the Open Label Extension (OLE).
ALXN2030 Dose B	ALXN2030	During the Double-Blind Treatment Period, participants will receive ALXN2030 dose B over 52 weeks. At Week 52, participants may continue into the OLE Period.
Placebo	Placebo	Placebo will be administered during the Double-Blind Treatment Period of 52 weeks.

Primary Outcome Measures

Name	Time	Method
Biopsy-proven histologic resolution	Week 52

Secondary Outcome Measures

Name	Time	Method
Biopsy-proven histologic resolution	Week 28
Change From Baseline in biopsy-proven histologic scores	Baseline, Weeks 28 and 52
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52	Baseline up to week 52
Annualized Total eGFR Slope	Baseline up to Week 52
Stabilized eGFR	Baseline up to Week 52
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs)	Day 1 up to Week 104
Number of Participants With Anti-drug Antibodies (ADAs)	Day 1 through Week 104
Plasma Concentration of ALXN2030	Baseline up to Week 104
Plasma Concentration of C3 Protein	Baseline up to Week 104
Change From Baseline in Serum Complement Functional Activity	Baseline, up to Week 52 and up to Week 104

Trial Locations

Locations (1)

Research Site; 🇨🇳 Taoyuan, Taiwan