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

Purpose

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.

Conditions

  • Antibody-Mediated Rejection
  • Kidney Transplantation
  • Biopsy-proven Histologic Scores
  • AMR

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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, < 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 immunosuppressant treatment which will be allowed and should be stable during the entire treatment.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo 		Placebo will be administered during the Double-Blind Treatment Period of 52 weeks.
  • Drug: Placebo
    Placebo will be administered SC.
Experimental
ALXN2030 Dose A 		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).
  • Drug: ALXN2030
    ALXN2030 will be administered subcutaneously (SC).
Experimental
ALXN2030 Dose B 		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.
  • Drug: ALXN2030
    ALXN2030 will be administered subcutaneously (SC).

Recruiting Locations

Research Site
Birmingham 4049979, Alabama 4829764 35249

Research Site
Los Angeles 5368361, California 5332921 90095

Research Site
Orange 5379513, California 5332921 92868

Research Site
Tampa 4174757, Florida 4155751 33606

Research Site
Livingston 5100572, New Jersey 5101760 07039

Research Site
New York 5128581, New York 5128638 10021

Research Site
New York 5128581, New York 5128638 10029

Research Site
Durham 4464368, North Carolina 4482348 27705

Research Site
Dallas 4684888, Texas 4736286 75235

Research Site
Richmond 4781708, Virginia 6254928 23298

More Details

Status
Recruiting
Sponsor
Alexion Pharmaceuticals, Inc.

Study Contact

Alexion Pharmaceuticals, Inc. (Sponsor)
1-855-752-2356
clinicaltrials@alexion.com

Detailed Description

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.