A study to determine if ALXN2030 is effective and safe in adults with antibody-mediated rejection after kidney transplantation (CONCORD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

29 Jan 2026 → ongoing

Decision date (initial)

2025-10-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alexion, AstraZeneca Rare Disease

External identifiers

EU CT number

2024-517498-25-00

ClinicalTrials.gov

NCT05501717

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Efficacy, Safety, Dose response

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

Secondary objectives 10

1. To evaluate the efficacy of ALXN2030 vs placebo on biopsy-proven histologic resolution in participants with active or chronic active AMR.
2. To evaluate the efficacy of ALXN2030 vs placebo on resolution of AMR activity in participants with active or chronic active AMR.
3. To evaluate the efficacy of ALXN2030 vs placebo on biopsy-proven histologic score in participants with active or chronic active AMR.
4. To evaluate the efficacy of ALXN2030 vs placebo on eGFR in participants with active or chronic active AMR.
5. To evaluate the efficacy of ALXN2030 vs placebo on total eGFR slope in participants with active or chronic active AMR.
6. To evaluate the efficacy of ALXN2030 vs placebo on eGFR stabilization in participants with active or chronic active AMR.
7. To assess the safety and tolerability of ALXN2030 in participants with active or chronic active AMR.
8. To characterize the PK of ALXN2030 in participants with active or chronic active AMR.
9. To characterize the PD of ALXN2030 in participants with active or chronic active AMR.
10. To assess the immunogenicity of ALXN2030 in participants with active or chronic active AMR.

Conditions and MedDRA coding

Antibody-Mediated Rejection after Kidney Transplantation

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. ≥ 18 to ≤ 75 years of age at the time of signing the informed consent.
2. Kidney transplant received ≥6 months prior to Screening.
3. Diagnosis of active or chronic active AMR according to Banff 2022 classification based on Screening kidney biopsy
4. Biopsy-proven histologic score ≥ 2 (g ≥ 1 and ptc ≥ 1) at Screening
5. eGFR ≥ 30 mL/min/1.73 m2 at Screening
6. Body weight ≥ 50 kg at Screening.
7. Male or female assigned at birth, inclusive of all gender identities.
8. CBP participants and CBP participants partners must follow protocol-specified contraception guidance.
9. Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
10. To reduce the risk of meningococcal infection (N meningitidis), all participants 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. Participants who do not meet this requirement will be vaccinated against meningococcal infection before receiving the first dose of study intervention. If vaccination occurs < 14 days prior to Day 1, the participants will receive prophylactic antibiotics for at least 14 days after meningococcal vaccination for serogroups A, C, W, Y (and B where available). Participants must agree to get revaccinated according to national/local guidelines.
11. Must be vaccinated for S pneumoniae prior to randomization according to current national/local vaccination guidelines.
12. Must be vaccinated for H influenzae type B (where available) prior to randomization according to current national/local vaccination guidelines. If vaccination is not clinically indicated due to the inability to mount an immune response, see Section 8.3.9 of the Protocol for instructions on antibiotic prophylactics.

Exclusion criteria 18

1. Biopsy-based diagnosis of any of the following at Screening: • TCMR, according to the Banff grade ≥ 1 (note: participants with borderline TCMR are eligible for the study) • Polyoma virus nephropathy • Severe thrombotic microangiopathy • Glomerulonephritis
2. ABO-incompatible transplant
3. Any of the following abnormal laboratory results at Screening: • 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
4. Multi-organ transplant recipient (except for simultaneous kidney-pancreas or previous multiple kidney transplants) or cell transplant (islet, bone marrow, stem cell) recipient.
5. Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.
6. 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.
7. Evidence of hepatitis B or hepatitis C infections according to the following criteria at Screening: • Testing positive for HBsAg, OR • Testing positive for HBcAb while having a negative HBsAb HBsAband HBV DNA by reflex testing detected above the LLOQ by the local or central laboratory at Screening. • Positive hepatitis C antibody test result at Screening or within 3 months unless HCV RNA negative test by local or central laboratory is documented.
8. Congenital immunodeficiency.
9. History of unexplained, recurrent infection.
10. Known medical or psychological conditions, including substance use disorder (including alcohol), or risk factor that, in the opinion of the Investigator, might interfere with the participant’s full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.
11. Hypersensitivity to any ingredient contained in the study intervention, including history of hypersensitivity to an oligonucleotide or GalNAc moiety.
12. Any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
13. Planned or recent treatments, < 90 days prior to the Screening Visit and during Screening, for Acute Rejection, AMR (including plasmapheresis, plasma exchange, IVIg, B-cell depleting therapy, interleukin inhibitors, proteasome inhibitors, high-dose corticosteroids [except for tapering]), HDS products with known hepatotoxic ingredients, TCMR (including T-cell depleting therapy), excluding the SoC treatment which will be allowed and should be stable during the entire treatment. The participant not on an immunosuppressive regimen containing a calcineurin inhibitor must be excluded.
14. Participation in another interventional treatment study or use of any experimental therapy within 90 days prior to Screening or within 5 half-lives of that investigational product, whichever is greater, or planned participation/use during the course of the study.
15. Pregnant, breastfeeding, or intending to conceive within 6 months after the last dose of study intervention.
16. Alanine transaminase (ALT) or aspartate transaminase (AST) > 2 × ULN or ratio AST/ALT > 0.8 when ALT or AST is abnormal (abnormal ALT or AST can be retested if between ULN and 2 × ULN).
17. 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).
18. Known current acute or active chronic liver disease eg. cirrhosis, MASH, fatty liver, and alcoholic hepatitis.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Biopsy-proven histologic resolution at Week 52

Secondary endpoints 10

1. Biopsy-proven histologic resolution at Week 28.
2. Resolution of AMR activity at Weeks 28 and 52.
3. Change from baseline in biopsy-proven histologic score at Weeks 28 and 52.
4. eGFR change from baseline at Week 52.
5. Annualized total eGFR slope during 52 weeks of treatment.
6. Stabilized eGFR (annualized eGFR slope > -1) during 52 weeks of treatment.
7. Incidence of TEAEs and TESAEs over time.
8. ALXN2030 plasma concentration over time.
9. Absolute values, change from Baseline and percent change from Baseline in plasma concentrations of C3 protein over time and in serum complement functional activity over time.
10. Anti-ALXN2030 Ab incidence, category of ADA response, and titer through the duration of the study.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

AstraZeneca Clinical Study Information Center

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications