Clazakizumab vs. Placebo - COVID-19 Infection

COVID-19 Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04494724
• Other study ID #: Pro00025969
• Status: Recruiting
• Phase: Phase 2
• Start date: July 13, 2020
• Est. completion date: July 31, 2021

Study information

• Verified date: July 2020
• Source: The Methodist Hospital System
• Contact: Isioma Agboli, MD
• Phone: 713-441-6311
• Email: iagboli[@]houstonmethodist.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >18 at the time of screening.

2. Participant or legally authorized representative (LAR) must be able to understand and provide informed consent.

3. 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.

4. C-reactive protein (CRP) > 3.5 mg/dL

5. Evidence of pulmonary involvement with at least 2 of the following:

1. oxygen saturation at rest in ambient air with peripheral capillary oxygen saturation (SpO2) = 94%

2. tachypnea with resting respiration rate > 25 breaths/minute

3. Partial pressure of oxygen (PaO2)/initial fraction of inspired oxygen (FiO2) = 300 mmHg

4. Chest imaging (radiograph, CT, or ultrasound) with abnormalities consistent COVID-19 pneumonia

Exclusion Criteria:

1. Previous hypersensitivity or allergic reactions to clazakizumab

2. Lactating or pregnant females

3. Patients with latent tuberculosis (TB) and who are not receiving treatment

4. Patients with active TB

5. Patients with known active inflammatory bowel disease, untreated diverticulitis, or gastrointestinal perforation

6. Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

7. 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

8. Participation in another clinical trial investigating COVID-19-aimed agents

9. Presence of any medical or psychosocial condition, which the investigator believes, would hinder adherence to the study requirements.

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19 Infection
• Infection

Intervention

Drug:
• Clazakizumab
Infusion
• Placebo
Infusion

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The Methodist Hospital System

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. Review. — View Citation

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 Au — View Citation

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. Ep — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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 Syndro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Endpoint	Proportion of participants who experience treatment-related adverse events (TEAE) = Grade 3 (CTCAE v5.0) during the first 24 hours after infusion of clazakizumab or placebo	24 hours
Secondary	Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO)	Proportion of participants who need mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) after the first dose of clazakizumab or placebo	14 days
Secondary	Infusion-related reactions during 24 hours from the time of infusion	Proportion of participants who experience infusion-related reactions during the first 24 hours after infusion of clazakizumab or placebo	24 hours
Secondary	Patient survival at 28 days	Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo	28 days
Secondary	Patient survival at 60 days	Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo	60 days
Secondary	Requirement for open-label clazakizumab	Proportion of participants who require an open-label dose of clazakizumab	14 days
Secondary	Time in the intensive care unit (ICU)	Number of days in the ICU following the first dose of clazakizumab or placebo	60 days
Secondary	Time in the hospital	Number of days in the hospital following the first dose of clazakizumab or placebo	60 days
Secondary	Time to mechanical ventilation	Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation	60 days
Secondary	Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14	Difference in WHO Clinical Progression Scale between clazakizumab and placebo	14 days
Secondary	Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28	Difference in WHO Clinical Progression Scale between clazakizumab and placebo	28 days
Secondary	Change in Radiologic Assessment of Lung Edema (RALE) at day 14	Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 14 from baseline between clazakizumab or placebo	14 days
Secondary	Change in Radiologic Assessment of Lung Edema (RALE) at day 28	Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 28 from baseline between clazakizumab or placebo	28 days