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

Alexion Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2

Conditions: Biopsy-proven Histologic Scores; Antibody-Mediated Rejection; Kidney Transplantation; AMR

Treatments: Drug: ALXN2030; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06744647

D8560C00002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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45 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo will be administered during the Double-Blind Treatment Period of 52 weeks.

Treatment:

Drug: Placebo

ALXN2030 Dose A

Experimental group

Description:

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).

Treatment:

Drug: ALXN2030

ALXN2030 Dose B

Experimental group

Description:

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.

Treatment:

Drug: ALXN2030