Clazakizumab Evidence: Trial Results and Peer-Reviewed Publications

Hipa.ai Research · Source: PubMed & ClinicalTrials.gov / AACT · Last updated:

The clinical evidence base for Clazakizumab comprises 39 peer-reviewed publications across 15 journals, 11 pivotal-trial primary-outcome rows reported to ClinicalTrials.gov, spanning indications including Asthma, COVID-19, Kidney Failure, Chronic, and Frailty. Most recent publication: The "Reducing Inflammation for Greater Health Trial (RIGHT)" Study-Concept, Rationale, and Design., J Am Geriatr Soc, 2026.

Top peer-reviewed publications

Curated set of pivotal-trial result papers and recent publications in high-tier journals.

  1. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.
    Wu C, Chen X, Cai Y, et al. · JAMA Intern Med · 2020
    PubMed: PMID 32167524 · NCT04494724 · COVID-19
  2. Interleukin-6: A Masterplayer in the Cytokine Network.
    Uciechowski P, Dempke WCM · Oncology · 2020
    PubMed: PMID 31958792 · NCT04494724 · COVID-19
  3. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases.
    Tanaka T, Kishimoto T · Int J Biol Sci · 2013
    PubMed: PMID 23136551 · NCT04494724 · COVID-19
  4. Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.
    Ruan Q, Yang K, Wang W, et al. · Intensive Care Med · 2020
    PubMed: PMID 32253449 · NCT04494724 · COVID-19
  5. COVID-19: consider cytokine storm syndromes and immunosuppression.
    Mehta P, McAuley DF, Brown M, et al. · Lancet · 2020
    PubMed: PMID 32192578 · NCT04494724 · COVID-19
  6. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome.
    Le RQ, Li L, Yuan W, et al. · Oncologist · 2019
    PubMed: PMID 29622697 · NCT04494724 · COVID-19
  7. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer.
    Jones SA, Jenkins BJ · Nat Rev Immunol · 2019
    PubMed: PMID 30254251 · NCT04494724 · COVID-19
  8. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19.
    Gao Y, Li T, Han M, et al. · J Med Virol · 2020
    PubMed: PMID 32181911 · NCT04494724 · COVID-19

Primary-outcome results across pivotal trials

Per-arm reported values from Phase 2/3 and Phase 3 trials with results posted to ClinicalTrials.gov.

TrialIndicationPrimary endpointArmValue
NCT03744910
IMAGINE
—Change From Baseline to Week 52 in Estimated Glomerular Filtration Rate (eGFR)
From Baseline to Week 52
Clazakizumab-8.0 milliliter per minute per 1.73 meter^2
Placebo-5.2 milliliter per minute per 1.73 meter^2
NCT03744910
IMAGINE
—Number of Participants Who Tested Positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV)
From baseline up to 4 years
Clazakizumab0 Participants
Clazakizumab0 Participants
Clazakizumab8 Participants
Clazakizumab0 Participants
Clazakizumab2 Participants
Clazakizumab5 Participants
Clazakizumab1 Participants
Clazakizumab3 Participants
Clazakizumab1 Participants
Placebo2 Participants
Placebo0 Participants
Placebo2 Participants
Placebo0 Participants
Placebo1 Participants
Placebo7 Participants
Placebo0 Participants
Placebo0 Participants
Placebo0 Participants
NCT03744910
IMAGINE
—Number of Participants With Abnormal Laboratory Test Results
Up to 4 years
Clazakizumab0 Participants
Clazakizumab5 Participants
Clazakizumab15 Participants
Clazakizumab11 Participants
Clazakizumab1 Participants
Clazakizumab0 Participants
Clazakizumab20 Participants
Clazakizumab33 Participants
Clazakizumab15 Participants
Clazakizumab7 Participants
Clazakizumab39 Participants
Clazakizumab1 Participants
Placebo2 Participants
Placebo5 Participants
Placebo21 Participants
Placebo6 Participants
Placebo0 Participants
Placebo0 Participants
Placebo6 Participants
Placebo0 Participants
Placebo1 Participants
Placebo4 Participants
Placebo10 Participants
Placebo0 Participants
NCT03744910
IMAGINE
—Number of Participants With Clinically Significant Change in Vital Signs, Electrocardiograms (ECGs), and Physical Examination
Up to 4 years
Clazakizumab0 Participants
Placebo0 Participants
NCT03744910
IMAGINE
—Number of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function
From Baseline to 4 years
Clazakizumab26 Participants
Placebo22 Participants
NCT03744910
IMAGINE
—Number of Participants With Positive Anti-drug Antibodies
Baseline, Weeks 12, 24, and 48
Clazakizumab5 Participants
Clazakizumab0 Participants
Clazakizumab3 Participants
Clazakizumab2 Participants
Placebo10 Participants
Placebo4 Participants
Placebo7 Participants
Placebo8 Participants
NCT03744910
IMAGINE
—Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and Adverse Events of Special Interest (AESIs)
Up to 4 years
Clazakizumab39 Participants
Clazakizumab56 Participants
Clazakizumab89 Participants
Placebo39 Participants
Placebo88 Participants
Placebo52 Participants
NCT03744910
IMAGINE
—Percentage of Participants With Abnormal Laboratory Test Results
Up to 4 years
Clazakizumab16.1 percentage of participants
Clazakizumab1.1 percentage of participants
Clazakizumab0 percentage of participants
Clazakizumab21.5 percentage of participants
Clazakizumab5.4 percentage of participants
Clazakizumab35.5 percentage of participants
Clazakizumab16.1 percentage of participants
Clazakizumab7.5 percentage of participants
Clazakizumab41.9 percentage of participants
Clazakizumab1.1 percentage of participants
Clazakizumab0 percentage of participants
Clazakizumab11.8 percentage of participants
Placebo0 percentage of participants
Placebo21.2 percentage of participants
Placebo1.0 percentage of participants
Placebo5.1 percentage of participants
Placebo10.1 percentage of participants
Placebo0 percentage of participants
Placebo6.1 percentage of participants
Placebo2.0 percentage of participants
Placebo0 percentage of participants
Placebo6.1 percentage of participants
Placebo0 percentage of participants
Placebo4.0 percentage of participants
NCT03744910
IMAGINE
—Percentage of Participants With Composite All-cause Allograft Loss or Irreversible Loss of Allograft Function
From Baseline to 4 years
Clazakizumab28.3 percentage of participants
Placebo22.2 percentage of participants
NCT03744910
IMAGINE
—Percentage of Participants With Positive Anti-drug Antibodies
Baseline, Weeks 12, 24, and 48
Clazakizumab4.1 percentage of participants
Clazakizumab0 percentage of participants
Clazakizumab2.9 percentage of participants
Clazakizumab5.7 percentage of participants
Placebo7.7 percentage of participants
Placebo10.3 percentage of participants
Placebo9.8 percentage of participants
Placebo9.7 percentage of participants
NCT03744910
IMAGINE
—Percentage of Participants With TEAEs, Serious TEAEs, and AESIs
Up to 4 years
Clazakizumab95.7 percentage of participants
Clazakizumab41.9 percentage of participants
Clazakizumab60.2 percentage of participants
Placebo39.0 percentage of participants
Placebo88.0 percentage of participants
Placebo52.0 percentage of participants

Publications by year

1994–2026: 39 publications.

1994
1
2005
1
2007
1
2009
1
2010
3
2013
1
2014
1
2017
6
2018
2
2019
5
2020
6
2021
3
2022
4
2023
1
2025
2
2026
1

Publications by indication

Asthma (17)

  • Estimating Individualized Treatment Rules Using Outcome Weighted Learning.
    J Am Stat Assoc · 2021 · PMID 23630406 · NCT04129931
  • Development and initial validation of the Asthma Severity Scoring System (ASSESS).
    J Allergy Clin Immunol · 2020 · PMID 31604088 · NCT04129931
  • Reinforcement Learning Trees.
    J Am Stat Assoc · 2019 · PMID 26903687 · NCT04129931
  • A novel endpoint for exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised controlled trials.
    Lancet Respir Med · 2018 · PMID 28583396 · NCT04129931
  • Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both.
    N Engl J Med · 2017 · PMID 28679092 · NCT04129931

COVID-19 (10)

  • A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.
    Crit Care Med · 2022 · PMID 35583232 · NCT04343989
  • SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
    Cochrane Database Syst Rev · 2021 · PMID 34473343 · NCT04494724
  • Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.
    JAMA Intern Med · 2020 · PMID 32167524 · NCT04494724
  • Interleukin-6: A Masterplayer in the Cytokine Network.
    Oncology · 2020 · PMID 31958792 · NCT04494724
  • Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.
    Intensive Care Med · 2020 · PMID 32253449 · NCT04494724

Kidney Failure, Chronic (2)

  • Early Versus Late Acute AMR in Kidney Transplant Recipients-A Comparison of Treatment Approaches and Outcomes From the ANZDATA Registry.
    Transplantation · 2025 · PMID 37322595 · NCT03380962
  • Assessment of Tocilizumab (Anti-Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients.
    Am J Transplant · 2018 · PMID 28199785 · NCT03380962

Frailty (1)

  • The "Reducing Inflammation for Greater Health Trial (RIGHT)" Study-Concept, Rationale, and Design.
    J Am Geriatr Soc · 2026 · PMID 41518612 · NCT05727384

Publications by journal

Trial-results highlights

In the NCT03744910 (IMAGINE) study, the change from baseline to week 52 in estimated glomerular filtration rate (eGFR) was observed. Participants receiving Clazakizumab had a change of -8.0 milliliter per minute per 1.73 meter^2, while those on placebo had a change of -5.2 milliliter per minute per 1.73 meter^2. Over up to 4 years in the same study, 26 participants in the Clazakizumab arm experienced composite all-cause allograft loss or irreversible loss of allograft function, compared to 22 participants in the placebo arm. No participants in either the Clazakizumab arm or the placebo arm showed clinically significant changes in vital signs, electrocardiograms (ECGs), or physical examination. Regarding participants who tested positive for Polyoma BK Virus (BKV), Cytomegalovirus (CMV), and Epstein-Barr Virus (EBV) up to 4 years in the Clazakizumab arm:

  • 0 participants tested positive for Polyoma BK Virus
  • 0 participants tested positive for Cytomegalovirus
  • 8 participants tested positive for Epstein-Barr Virus
  • 0 participants
  • 2 participants
  • 5 participants

The NCT03744910 study also reported on adverse events and laboratory findings. Up to 4 years, the number of participants with treatment-emergent adverse events (TEAEs) was 39 in the Clazakizumab arm and 39 in the placebo arm. For serious TEAEs, there were 56 participants in the Clazakizumab arm and 88 in the placebo arm. Adverse events of special interest (AESIs) were reported in 89 participants receiving Clazakizumab and 52 participants receiving placebo. The number of participants with abnormal laboratory test results in the Clazakizumab arm included:

  • 0 participants
  • 5 participants
  • 15 participants
  • 11 participants
  • 1 participant
  • 0 participants
Percentages of participants with abnormal laboratory test results in the Clazakizumab arm included:
  • 16.1% of participants
  • 1.1% of participants
  • 0% of participants
  • 21.5% of participants
  • 5.4% of participants
  • 35.5% of participants
For positive anti-drug antibodies, participants in the Clazakizumab arm had counts of 5, 0, 3, and 2 at various time points, while the placebo arm had counts of 10 and 4.

All values presented here are sourced from primary registry reporting. For clinical decisions, individual published papers should be consulted.

All Clazakizumab publications (39)

2026 (1 paper)

  1. The "Reducing Inflammation for Greater Health Trial (RIGHT)" Study-Concept, Rationale, and Design.
    Sattui SE, Bertolet M, Forman DE, et al. · J Am Geriatr Soc · 2026 · Derived
    PubMed: PMID 41518612 · NCT05727384 (RIGHT) · Frailty

2025 (2 papers)

  1. Poised for Innovation: Considerations for End Points for New Drug Development in Kidney Transplantation.
    Mannon RB, Vincenti FG · J Am Soc Nephrol · 2025 · Derived
    PubMed: PMID 39102302 · NCT03744910 (IMAGINE)
  2. Early Versus Late Acute AMR in Kidney Transplant Recipients-A Comparison of Treatment Approaches and Outcomes From the ANZDATA Registry.
    Fernando SC, Polkinghorne KR, Lim WH, et al. · Transplantation · 2025 · Derived
    PubMed: PMID 37322595 · NCT03380962 · Kidney Failure, Chronic

2023 (1 paper)

  1. Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Renal Allograft Rejection: Accumulation of Antibody-neutralized Interleukin-6 Without Signs of Proinflammatory Rebound Phenomena.
    Borski A, Eskandary F, Haindl S, et al. · Transplantation · 2023 · Derived
    PubMed: PMID 35969004 · NCT03744910 (IMAGINE)

2022 (4 papers)

  1. Clazakizumab for the treatment of chronic active antibody-mediated rejection (AMR) in kidney transplant recipients: Phase 3 IMAGINE study rationale and design.
    Nickerson PW, Böhmig GA, Chadban S, et al. · Trials · 2022 · Derived
    PubMed: PMID 36550562 · NCT03744910 (IMAGINE)
  2. Anti-interleukin-6 Antibody Clazakizumab in Antibody-mediated Kidney Transplant Rejection: Effect on Donor-derived Cell-free DNA and C-X-C Motif Chemokine Ligand 10.
    Mayer KA, Doberer K, Halloran PF, et al. · Transplant Direct · 2022 · Derived
    PubMed: PMID 36382130 · NCT03444103
  3. A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.
    Lonze BE, Spiegler P, Wesson RN, et al. · Crit Care Med · 2022 · Derived
    PubMed: PMID 35583232 · NCT04343989 · COVID-19
  4. 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, et al. · Kidney Int Rep · 2022 · Derived
    PubMed: PMID 35497778 · NCT03744910 (IMAGINE)

2021 (3 papers)

  1. Anti-interleukin-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection: effect on cytochrome P450 drug metabolism.
    Mühlbacher J, Schörgenhofer C, Doberer K, et al. · Transpl Int · 2021 · Derived
    PubMed: PMID 34153143 · NCT03444103
  2. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19.
    Kreuzberger N, Hirsch C, Chai KL, et al. · Cochrane Database Syst Rev · 2021 · Derived
    PubMed: PMID 34473343 · NCT04494724 · COVID-19
  3. Estimating Individualized Treatment Rules Using Outcome Weighted Learning.
    Zhao Y, Zeng D, Rush AJ, et al. · J Am Stat Assoc · 2021 · Background
    PubMed: PMID 23630406 · NCT04129931 · Asthma

2020 (6 papers)

  1. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China.
    Wu C, Chen X, Cai Y, et al. · JAMA Intern Med · 2020 · Trial result
    PubMed: PMID 32167524 · NCT04494724 · COVID-19
  2. Interleukin-6: A Masterplayer in the Cytokine Network.
    Uciechowski P, Dempke WCM · Oncology · 2020 · Trial result
    PubMed: PMID 31958792 · NCT04494724 · COVID-19
  3. Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.
    Ruan Q, Yang K, Wang W, et al. · Intensive Care Med · 2020 · Trial result
    PubMed: PMID 32253449 · NCT04494724 · COVID-19
  4. COVID-19: consider cytokine storm syndromes and immunosuppression.
    Mehta P, McAuley DF, Brown M, et al. · Lancet · 2020 · Trial result
    PubMed: PMID 32192578 · NCT04494724 · COVID-19
  5. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19.
    Gao Y, Li T, Han M, et al. · J Med Virol · 2020 · Trial result
    PubMed: PMID 32181911 · NCT04494724 · COVID-19
  6. Development and initial validation of the Asthma Severity Scoring System (ASSESS).
    Fitzpatrick AM, Szefler SJ, Mauger DT, et al. · J Allergy Clin Immunol · 2020 · Background
    PubMed: PMID 31604088 · NCT04129931 · Asthma

2019 (5 papers)

  1. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome.
    Le RQ, Li L, Yuan W, et al. · Oncologist · 2019 · Trial result
    PubMed: PMID 29622697 · NCT04494724 · COVID-19
  2. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer.
    Jones SA, Jenkins BJ · Nat Rev Immunol · 2019 · Trial result
    PubMed: PMID 30254251 · NCT04494724 · COVID-19
  3. Clazakizumab in late antibody-mediated rejection: study protocol of a randomized controlled pilot trial.
    Eskandary F, Dürr M, Budde K, et al. · Trials · 2019 · Derived
    PubMed: PMID 30635033 · NCT03444103
  4. Reinforcement Learning Trees.
    Zhu R, Zeng D, Kosorok MR, et al. · J Am Stat Assoc · 2019 · Background
    PubMed: PMID 26903687 · NCT04129931 · Asthma
  5. A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection.
    Eskandary F, Regele H, Baumann L, et al. · J Am Soc Nephrol · 2019 · Background
    PubMed: PMID 29242250 · NCT03444103

2018 (2 papers)

  1. A novel endpoint for exacerbations in asthma to accelerate clinical development: a post-hoc analysis of randomised controlled trials.
    Fuhlbrigge AL, Bengtsson T, Peterson S, et al. · Lancet Respir Med · 2018 · Background
    PubMed: PMID 28583396 · NCT04129931 · Asthma
  2. Assessment of Tocilizumab (Anti-Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients.
    Choi J, Aubert O, Vo A, et al. · Am J Transplant · 2018 · Background
    PubMed: PMID 28199785 · NCT03380962 · Kidney Failure, Chronic

2017 (6 papers)

  1. Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both.
    Woodcock J, LaVange LM · N Engl J Med · 2017 · Background
    PubMed: PMID 28679092 · NCT04129931 · Asthma
  2. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study.
    Waljee AK, Rogers MA, Lin P, et al. · BMJ · 2017 · Background
    PubMed: PMID 28404617 · NCT04129931 · Asthma
  3. Effects of Age and Disease Severity on Systemic Corticosteroid Responses in Asthma.
    Phipatanakul W, Mauger DT, Sorkness RL, et al. · Am J Respir Crit Care Med · 2017 · Background
    PubMed: PMID 27967215 · NCT04129931 · Asthma
  4. The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase IIb Study of Adults With Active Psoriatic Arthritis.
    Mease PJ, Gottlieb AB, Berman A, et al. · Arthritis Rheumatol · 2017 · Background
    PubMed: PMID 27059799 · NCT03444103
  5. Severe and Difficult-to-Treat Asthma in Adults.
    Israel E, Reddel HK · N Engl J Med · 2017 · Background
    PubMed: PMID 28877019 · NCT04129931 · Asthma
  6. The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis.
    de Wit HM, Te Groen M, Rovers MM, et al. · Br J Clin Pharmacol · 2017 · Background
    PubMed: PMID 26935973 · NCT04129931 · Asthma

2014 (1 paper)

  1. The placebo effect in asthma.
    Dutile S, Kaptchuk TJ, Wechsler ME, et al. · Curr Allergy Asthma Rep · 2014 · Background
    PubMed: PMID 24951239 · NCT04129931 · Asthma

2013 (1 paper)

  1. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases.
    Tanaka T, Kishimoto T · Int J Biol Sci · 2013 · Trial result
    PubMed: PMID 23136551 · NCT04494724 · COVID-19

2010 (3 papers)

  1. Tiotropium bromide step-up therapy for adults with uncontrolled asthma.
    Peters SP, Kunselman SJ, Icitovic N, et al. · N Engl J Med · 2010 · Background
    PubMed: PMID 20979471 · NCT04129931 · Asthma
  2. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program.
    Moore WC, Meyers DA, Wenzel SE, et al. · Am J Respir Crit Care Med · 2010 · Background
    PubMed: PMID 19892860 · NCT04129931 · Asthma
  3. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids.
    Lemanske RF, Mauger DT, Sorkness CA, et al. · N Engl J Med · 2010 · Background
    PubMed: PMID 20197425 · NCT04129931 · Asthma

2009 (1 paper)

  1. Randomized trial of the effect of drug presentation on asthma outcomes: the American Lung Association Asthma Clinical Research Centers.
    Wise RA, Bartlett SJ, Brown ED, et al. · J Allergy Clin Immunol · 2009 · Background
    PubMed: PMID 19632710 · NCT04129931 · Asthma

2007 (1 paper)

  1. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial.
    Sorkness CA, Lemanske RF, Mauger DT, et al. · J Allergy Clin Immunol · 2007 · Background
    PubMed: PMID 17140647 · NCT04129931 · Asthma

2005 (1 paper)

  1. An experimental design for the development of adaptive treatment strategies.
    Murphy SA · Stat Med · 2005 · Background
    PubMed: PMID 15586395 · NCT04129931 · Asthma

1994 (1 paper)

  1. The validity and reproducibility of a work productivity and activity impairment instrument.
    Reilly MC, Zbrozek AS, Dukes EM, et al. · Pharmacoeconomics · 1994 · Background
    PubMed: PMID 10146874 · NCT04129931 · Asthma

Sources and methodology

This page summarizes published evidence for general reference and does not constitute medical advice. For clinical decisions, consult the linked primary publications and your healthcare provider. Data sourced from PubMed and the ClinicalTrials.gov / AACT database maintained by the Clinical Trials Transformation Initiative (CTTI).