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NCT03744910: IMAGINE

Clazakizumab for the Treatment of Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients

Terminated Phase 3 Results posted Last updated 23 July 2025
What this trial tests

Phase 3 trial testing Clazakizumab in Antibody-mediated Rejection in 194 participants. Terminated before completion.

Timeline
14 October 2019
Primary endpoint
8 April 2024
8 April 2024

Quick facts

Lead sponsorCSL Behring
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment194
Start date14 October 2019
Primary completion8 April 2024
Estimated completion8 April 2024
Sites142 locations across France, New Zealand, Netherlands, Belgium, Austria, Sweden, Taiwan, Germany

Drugs / interventions tested

Conditions studied

Sponsor

CSL Behring — full company profile →

Who can join

Adults 18 to 75, any sex, with Antibody-mediated Rejection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR) Primary · From Baseline to Week 52

This primary outcome measure was the one from the first interim analysis.

GroupValue95% CI
Clazakizumab-8.0-10.2 – -5.8
Placebo-5.2-7.4 – -3.1
Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function Primary · From Baseline to 4 years

Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: * eGFR \< 15 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2)\* * return to dialysis\* * allograft nephrectomy * retransplantation * death from any cause, or * a sustained (greater than or equal to \[\>=\] 60 days) 40% decline in eGFR from Baseline. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value m

GroupValue95% CI
Clazakizumab26
Placebo22
Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function Primary · From Baseline to 4 years

Composite all-cause allograft loss or irreversible loss of allograft function, defined as time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation * death from any cause, or * a sustained (greater than or equal to \[\>=\] 60 days) 40% decline in eGFR from Baseline. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must

GroupValue95% CI
Clazakizumab28.3
Placebo22.2
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs) Primary · Up to 4 years
TEAEs
GroupValue95% CI
Clazakizumab89
Placebo88
Serious TEAEs
GroupValue95% CI
Clazakizumab39
Placebo39
AESIs
GroupValue95% CI
Clazakizumab56
Placebo52
Percentage of Participants With TEAEs, Serious TEAEs, and AESIs Primary · Up to 4 years
TEAEs
GroupValue95% CI
Clazakizumab95.7
Placebo88.0
Serious TEAEs
GroupValue95% CI
Clazakizumab41.9
Placebo39.0
AESIs
GroupValue95% CI
Clazakizumab60.2
Placebo52.0
Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Primary · From baseline up to 4 years

Number of participants who tested positive for BKV, CMV or EBV according to the maximum measured viral amount (International Units/mL \[IU/mL\]) after baseline are reported here.

BKV >Lower limit of quantification (LLOQ) to <320 IU/mL
GroupValue95% CI
Clazakizumab3
Placebo2
BKV >=320 IU/mL to <3200 IU/mL
GroupValue95% CI
Clazakizumab1
Placebo0
BKV >=3200 IU/mL
GroupValue95% CI
Clazakizumab1
Placebo0
CMV >LLOQ to <1000 IU/mL
GroupValue95% CI
Clazakizumab5
Placebo1
CMV >=1000 IU/mL to <5000 IU/mL
GroupValue95% CI
Clazakizumab2
Placebo2
CMV >=5000 IU/mL
GroupValue95% CI
Clazakizumab0
Placebo0
EBV >LLOQ to <10200 IU/mL
GroupValue95% CI
Clazakizumab8
Placebo7
EBV >=10200 IU/mL to <20400 IU/mL
GroupValue95% CI
Clazakizumab0
Placebo0
Number of Participants With Abnormal Laboratory Test Results Primary · Up to 4 years

Laboratory tests included liver function test (LFTs), complete blood count (CBC), plasma lipids, high-sensitivity C-reactive protein (hsCRP). Only participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase.

ALT : >ULN to 3 x ULN
GroupValue95% CI
Clazakizumab15
Placebo6
ALT : > 3 to 5 × ULN
GroupValue95% CI
Clazakizumab0
Placebo1
AST : >ULN to 3 x ULN
GroupValue95% CI
Clazakizumab11
Placebo4
AST : > 3 to 5 × ULN
GroupValue95% CI
Clazakizumab1
Placebo0
AST : > 5 × ULN
GroupValue95% CI
Clazakizumab0
Placebo2
Bilirubin: > ULN to 2 × ULN
GroupValue95% CI
Clazakizumab20
Placebo6
Bilirubin: > 2 × ULN
GroupValue95% CI
Clazakizumab5
Placebo0
Neutrophils: < 2.5 to 1.5 10^9/L
GroupValue95% CI
Clazakizumab33
Placebo21
Percentage of Participants With Abnormal Laboratory Test Results Primary · Up to 4 years

Laboratory tests included LFTs, CBC, plasma lipids, hsCRP. Only percentage of participants with abnormal laboratory test results are reported here. Here, ULN = upper limit of normal, LLN = lower limit of normal, ALT = Alanine aminotransferase and AST = Aspartate aminotransferase.

ALT : >ULN to 3 x ULN
GroupValue95% CI
Clazakizumab16.1
Placebo6.1
ALT : > 3 to 5 × ULN
GroupValue95% CI
Clazakizumab0
Placebo1.0
AST : >ULN to 3 x ULN
GroupValue95% CI
Clazakizumab11.8
Placebo4.0
AST : > 3 to 5 × ULN
GroupValue95% CI
Clazakizumab1.1
Placebo0
AST : > 5 × ULN
GroupValue95% CI
Clazakizumab0
Placebo2.0
Bilirubin: > ULN to 2 × ULN
GroupValue95% CI
Clazakizumab21.5
Placebo6.1
Bilirubin: > 2 × ULN
GroupValue95% CI
Clazakizumab5.4
Placebo0
Neutrophils: < 2.5 to 1.5 10^9/L
GroupValue95% CI
Clazakizumab35.5
Placebo21.2
Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination Primary · Up to 4 years
GroupValue95% CI
Clazakizumab0
Placebo0
Number of Participants With Positive Anti-drug Antibodies Primary · Baseline, Weeks 12, 24, and 48
Baseline
GroupValue95% CI
Clazakizumab5
Placebo10
Week 12
GroupValue95% CI
Clazakizumab3
Placebo8
Week 24
GroupValue95% CI
Clazakizumab2
Placebo7
Week 48
GroupValue95% CI
Clazakizumab0
Placebo4
Percentage of Participants With Positive Anti-drug Antibodies Primary · Baseline, Weeks 12, 24, and 48
Baseline
GroupValue95% CI
Clazakizumab5.7
Placebo10.3
Week 12
GroupValue95% CI
Clazakizumab4.1
Placebo9.8
Week 24
GroupValue95% CI
Clazakizumab2.9
Placebo9.7
Week 48
GroupValue95% CI
Clazakizumab0
Placebo7.7
Number of Participants With Composite All-cause Allograft Loss Secondary · From Baseline to 4 years

Composite all-cause allograft loss, defined as, time to first occurrence of any of the following components: * eGFR \< 15 mL/min/1.73 m\^2\* * return to dialysis\* * allograft nephrectomy * retransplantation, or * death from any cause. (\*Total cumulative duration of sustained eGFR \< 15 mL/min/1.73 m\^2 AND / OR dialysis \>= 60 days.) If the eGFR \< 15 mL/min/1.73 m\^2 was the only component reached, the value must be sustained over at least 60 days and must be confirmed by a repeat measurement after \>= 60 days from the first measurement. The number of participants with composite all-cause

GroupValue95% CI
Clazakizumab17
Placebo14

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 4 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Clazakizumab
Serious: 39/93 (42%)
Deaths: 3/93
Placebo
Serious: 39/100 (39%)
Deaths: 1/100

Serious adverse events (108 terms)

ReactionSystemClazakizumabPlacebo
COVID-19Infections and infestations
Acute kidney injuryRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
COVID-19 pneumoniaInfections and infestations
GastroenteritisInfections and infestations
Clostridium difficile infectionInfections and infestations
Urinary tract infectionInfections and infestations
Renal impairmentRenal and urinary disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Transplant rejectionImmune system disorders
Chest painGeneral disorders
Acute myocardial infarctionCardiac disorders
Cytomegalovirus infectionInfections and infestations
InfluenzaInfections and infestations
Arteriovenous graft site infectionInfections and infestations
Arthritis bacterialInfections and infestations
Atypical pneumoniaInfections and infestations
BacteraemiaInfections and infestations
BacteriuriaInfections and infestations
Clostridium difficile colitisInfections and infestations
Coronavirus infectionInfections and infestations
Cytomegalovirus colitisInfections and infestations
DiverticulitisInfections and infestations
Other adverse events (43 terms — click to expand)

ReactionSystemClazakizumabPlacebo
COVID-19Infections and infestations
Oedema peripheralGeneral disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
HyperkalaemiaMetabolism and nutrition disorders
Blood creatinine increasedInvestigations
HypertensionVascular disorders
Urinary tract infectionInfections and infestations
NasopharyngitisInfections and infestations
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders
HyperlipidaemiaMetabolism and nutrition disorders
Upper respiratory tract infectionInfections and infestations
LeukopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
Acute kidney injuryRenal and urinary disorders
ProteinuriaRenal and urinary disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
HyperphosphataemiaMetabolism and nutrition disorders
Renal impairmentRenal and urinary disorders
Herpes zosterInfections and infestations
Abdominal pain upperGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Immunosuppressant drug level decreasedInvestigations
Immunosuppressant drug level increasedInvestigations
Weight decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
Metabolic acidosisMetabolism and nutrition disorders
Iron deficiencyMetabolism and nutrition disorders
AstheniaGeneral disorders
Blood bilirubin increasedInvestigations
Neutrophil count decreasedInvestigations

Most-reported serious reactions: COVID-19, Acute kidney injury, Diarrhoea, Pneumonia, Anaemia, COVID-19 pneumonia, Gastroenteritis, Clostridium difficile infection.

Data from ClinicalTrials.gov NCT03744910 adverse events section.

Sponsor's own description

This trial investigates the efficacy and safety of clazakizumab \[an anti-interleukin (IL)-6 monoclonal antibody (mAb)\] for the treatment of CABMR in recipients of a kidney transplant.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  2. Antibodies to watch in 2019.
    Kaplon H, Reichert JM. · · 2019 · cited 324× · PMID 30516432 · DOI 10.1080/19420862.2018.1556465
  3. Antibodies to watch in 2021.
    Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
  4. A Randomized Clinical Trial of Anti-IL-6 Antibody Clazakizumab in Late Antibody-Mediated Kidney Transplant Rejection.
    Doberer K, Duerr M, Halloran PF, Eskandary F, et al · · 2021 · cited 137× · PMID 33443079 · DOI 10.1681/asn.2020071106
  5. The therapeutic challenge of late antibody-mediated kidney allograft rejection.
    Böhmig GA, Eskandary F, Doberer K, Halloran PF. · · 2019 · cited 87× · PMID 30955215 · DOI 10.1111/tri.13436
  6. Tackling Chronic Kidney Transplant Rejection: Challenges and Promises.
    Lai X, Zheng X, Mathew JM, Gallon L, et al · · 2021 · cited 66× · PMID 34093552 · DOI 10.3389/fimmu.2021.661643
  7. IL-6 Directed Therapy in Transplantation.
    Miller CL, Madsen JC. · · 2021 · cited 50× · PMID 34099967 · DOI 10.1007/s40472-021-00331-4
  8. Evaluation of Clazakizumab (Anti-Interleukin-6) in Patients With Treatment-Resistant Chronic Active Antibody-Mediated Rejection of Kidney Allografts.
    Jordan SC, Ammerman N, Choi J, Huang E, et al · · 2022 · cited 37× · PMID 35497778 · DOI 10.1016/j.ekir.2022.01.1074

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Other trials of Clazakizumab

Trials testing the same drug.

Other recruiting trials for Antibody-mediated Rejection

Currently open trials in the same condition.

Other CSL Behring trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03744910.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing