Clazakizumab vs. Placebo - COVID-19 Infection

Официальное название

A Phase 2 Trial to Evaluate the Safety and Tolerability of Clazakizumab® [Anti-Interleukin (IL)-6 Monoclonal] Compared to Placebo for the Treatment of COVID-19 Infection

Обзор

The purpose of this study is to investigate the effectiveness and safety of treatment with clazakizumab compared to a placebo (inactive substance). We are proposing to try this drug to treat coronavirus disease 2019 (COVID-19) infection. Patients with COVID-19 infection have been shown to have increases in certain inflammatory processes. Clazakizumab is an antibody (immune system protein) that blocks certain inflammatory processes. The treatment plan is to attempt to inhibit or block these inflammatory processes in order to try to limit the damage COVID-19 causes to the lungs.

Подробное описание

The purpose of this randomized, double-blind, placebo-controlled trial is to evaluate the safety and efficacy of clazakizumab vs placebo for the prevention of acute respiratory distress syndrome (ARDS) in patients with COVID-19 and pulmonary manifestations. The study will compare clazakizumab to placebo in a randomized, double-blind fashion followed by an open-label dose of clazakizumab if there is no improvement or a worsening of condition occurs after 24-hours or anytime during the first 14 days after the first dose of clazakizumab or placebo. We hypothesize that clazakizumab will be safely tolerated and will reduce the risk of progression of COVID-19 to acute respiratory distress syndrome.

Primary Objective:

• To evaluate the safety and tolerability of clazakizumab vs placebo for the treatment of patients with COVID-19 disease and signs of pulmonary involvement

Sixty adult patients with COVID-19 and signs of pulmonary involvement at Houston Methodist who are not in need of ventilator support at the time of enrollment.

Вмешательства

• Препарат Clazakizumab
  Infusion
• Препарат Placebo
  Infusion

Первичные конечные точки

• Primary Endpoint [Срок оценки: 24 hours]

Вторичные конечные точки (12)

• Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) [Срок оценки: 14 days]
• Infusion-related reactions during 24 hours from the time of infusion [Срок оценки: 24 hours]
• Patient survival at 28 days [Срок оценки: 28 days]
• Patient survival at 60 days [Срок оценки: 60 days]
• Requirement for open-label clazakizumab [Срок оценки: 14 days]
• Time in the intensive care unit (ICU) [Срок оценки: 60 days]
• Time in the hospital [Срок оценки: 60 days]
• Time to mechanical ventilation [Срок оценки: 60 days]
• Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14 [Срок оценки: 14 days]
• Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28 [Срок оценки: 28 days]
• Change in Radiologic Assessment of Lung Edema (RALE) at day 14 [Срок оценки: 14 days]
• Change in Radiologic Assessment of Lung Edema (RALE) at day 28 [Срок оценки: 28 days]

Критерии участия

Критерии включения

• Age >18 at the time of screening.
• Participant or legally authorized representative (LAR) must be able to understand and provide informed consent.
• Hospitalized with coronavirus disease (COVID-19) confirmed by polymerase chain reaction (PCR) assay from any specimen (eg, respiratory, blood, urine, stool, other bodily fluid) within the prior 72 hours.
• C-reactive protein (CRP) > 3.5 mg/dL
• Evidence of pulmonary involvement with at least 2 of the following:

• oxygen saturation at rest in ambient air with peripheral capillary oxygen saturation (SpO2) ≤ 94%
• tachypnea with resting respiration rate > 25 breaths/minute
• Partial pressure of oxygen (PaO2)/initial fraction of inspired oxygen (FiO2) ≤ 300 mmHg
• Chest imaging (radiograph, CT, or ultrasound) with abnormalities consistent COVID-19 pneumonia

Критерии исключения

• Previous hypersensitivity or allergic reactions to clazakizumab
• Lactating or pregnant females
• Patients with latent tuberculosis (TB) and who are not receiving treatment
• Patients with active TB
• Patients with known active inflammatory bowel disease, untreated diverticulitis, or gastrointestinal perforation
• Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
• A significantly abnormal general serum screening lab result defined as a white blood cell (WBC) count < 3.0 X 10\^3/mL, a hemoglobin (Hgb) < 8.0 g/dL, a platelet count < 50 X 10\^3/mL, an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit normal
• Participation in another clinical trial investigating COVID-19-aimed agents
• Presence of any medical or psychosocial condition, which the investigator believes, would hinder adherence to the study requirements.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Houston Methodist Hospital — Houston

Публикации

• Jones SA, Jenkins BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol. 2018 Dec;18(12):773-789. doi: 10.1038/s41577-018-0066-7. PMID 30254251
• Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int J Biol Sci. 2012;8(9):1227-36. doi: 10.7150/ijbs.4666. Epub 2012 Oct 24. PMID 23136551
• Uciechowski P, Dempke WCM. Interleukin-6: A Masterplayer in the Cytokine Network. Oncology. 2020;98(3):131-137. doi: 10.1159/000505099. Epub 2020 Jan 20. PMID 31958792
• Ruan Q, Yang K, Wang W, Jiang L, Song J. 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 Jun;46(6):1294-1297. doi: 10.1007/s00134-020-06028-z. PMID 32253449
• Gao Y, Li T, Han M, Li X, Wu D, Xu Y, Zhu Y, Liu Y, Wang X, Wang L. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol. 2020 Jul;92(7):791-796. doi: 10.1002/jmv.25770. Epub 2020 Apr 10. PMID 32181911
• Le RQ, Li L, Yuan W, Shord SS, Nie L, Habtemariam BA, Przepiorka D, Farrell AT, Pazdur R. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. Oncologist. 2018 Aug;23(8):943-947. doi: 10.1634/theoncologist.2018-0028. Epub 2018 Apr 5. PMID 29622697
• Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available. PMID 32192578
• Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamain PMID 32167524

Идентификаторы

NCT: NCT04494724 · Pro00025969

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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