Dataset Information

A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.

ABSTRACT:

Objectives

We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.

Design

Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.

Setting

Five U.S. medical centers.

Patients

Adults inpatients with severe COVID-19 disease and hyperinflammation.

Interventions

Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo.

Measurements and main results

The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively).

Conclusions

Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

SUBMITTER: Lonze BE

PROVIDER: S-EPMC9380150 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.

Lonze Bonnie E BE Spiegler Peter P Wesson Russell N RN Alachkar Nada N Petkova Eva E Weldon Elaina P EP Dieter Rebecca A RA Li Yi Y Quinn Max M Mattoo Aprajita A Soomro Irfana I Cohen Steven M SM Leung Sherry S Deterville Cecilia L CL Landrum B Mark BM Ali Muhammad Imran MI Cohen David J DJ Singer Andrew L AL Sen Ayan A Chong Edward E Hochman Judith S JS Troxel Andrea B AB Montgomery Robert A RA

Critical care medicine 20220517 9

<h4>Objectives</h4>We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.<h4>Design</h4>Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.<h4>Setting</h4>Five U.S. medical centers.<h4>Patients</h4>Adults inpatients with severe COVID-19 disease and hyperinflammation.<h4>Interventions</h4>Eighty-one patients enrolled in pha ...[more]

PMID: 35583232

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Dataset Information

A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.

Objectives

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.

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