Clinical trial NCT06744647: Phase 2 Study of ALXN2030 in Patients With Antibody-Mediated Rejection After Kidney Transplantation
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of ALXN2030 in Adult Patients With Antibody-Mediated Rejection After Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Antibody-Mediated Rejection
Kidney Transplantation
Biopsy-proven Histologic Scores
AMR
Keywords: ALXN2030
Antibody-Mediated Rejection
Kidney Transplantation
Biopsy-proven histologic scores
AMR
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2024-12-20
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Biopsy-proven histologic resolution
timeFrame: Week 52
Secondary outcomes:
measure: Biopsy-proven histologic resolution
timeFrame: Week 28
measure: Change From Baseline in biopsy-proven histologic scores
timeFrame: Baseline, Weeks 28 and 52
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 52
timeFrame: Baseline up to week 52
measure: Annualized Total eGFR Slope
timeFrame: Baseline up to Week 52
measure: Stabilized eGFR
timeFrame: Baseline up to Week 52
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 up to Week 104
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Day 1 through Week 104
measure: Plasma Concentration of ALXN2030
timeFrame: Baseline up to Week 104
measure: Plasma Concentration of C3 Protein
timeFrame: Baseline up to Week 104
measure: Change From Baseline in Serum Complement Functional Activity
timeFrame: Baseline, up to Week 52 and up to Week 104
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Livingston
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Botucatu
country: Brazil
facility: Research Site
city: Campinas
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: London
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Changsha
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Kaohsiung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: