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
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo |
Placebo will be administered during the Double-Blind Treatment Period of 52 weeks. |
|
|
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). |
|
|
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. |
|
Recruiting Locations
Birmingham 4049979, Alabama 4829764 35249
Los Angeles 5368361, California 5332921 90095
Orange 5379513, California 5332921 92868
Tampa 4174757, Florida 4155751 33606
Livingston 5100572, New Jersey 5101760 07039
New York 5128581, New York 5128638 10021
New York 5128581, New York 5128638 10029
Durham 4464368, North Carolina 4482348 27705
Dallas 4684888, Texas 4736286 75235
Richmond 4781708, Virginia 6254928 23298
More Details
- Status
- Recruiting
- Sponsor
- Alexion Pharmaceuticals, Inc.
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.