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Clazakizumab vs. Placebo - COVID-19 Infection

Primary Purpose

COVID-19 Infection

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Clazakizumab

Placebo

About this trial

This is an interventional treatment trial for COVID-19 Infection focused on measuring COVID-19, coronavirus infection, respiration, artificial, extracorporeal membrane oxygenation, randomized controlled trial, respiratory distress syndrome, adult

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
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:

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.

Sites / Locations

Houston Methodist HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Clazakizumab

Placebo

Arm Description

Clazakizumab - 25mg in 50 milliliters (mL) of 0.9% saline, IV infusion over 30 minutes.

Placebo - 50 mL 0.9% saline, IV infusion over 30 minutes.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

Patient survival at 28 days

Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo

Patient survival at 60 days

Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo

Requirement for open-label clazakizumab

Proportion of participants who require an open-label dose of clazakizumab

Time in the intensive care unit (ICU)

Number of days in the ICU following the first dose of clazakizumab or placebo

Time in the hospital

Number of days in the hospital following the first dose of clazakizumab or placebo

Time to mechanical ventilation

Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation

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

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

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

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

Full Information

NCT ID

NCT04494724

First Posted

July 21, 2020

Last Updated

July 30, 2020

Sponsor

The Methodist Hospital Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT04494724

Brief Title

Clazakizumab vs. Placebo - COVID-19 Infection

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Unknown status

Study Start Date

July 13, 2020 (Actual)

Primary Completion Date

December 31, 2020 (Anticipated)

Study Completion Date

July 31, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The Methodist Hospital Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19 Infection

Keywords

COVID-19, coronavirus infection, respiration, artificial, extracorporeal membrane oxygenation, randomized controlled trial, respiratory distress syndrome, adult

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

This single-site, phase 2 randomized, double-blind, placebo-controlled trial is designed to administer a single dose of clazakizumab or placebo on day 0. If, after 24 hours or up to 14 days from the first infusion, the participant's condition worsens or does not improve, the investigator may elect to provide a single, open-label dose of clazakizumab regardless of the initial group assignment. All except the investigational pharmacist will remain blinded as to the initial group assignment until data lock.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Blinded to all except investigational pharmacy. Only the optional second infusion, if determined necessary to administer, will be open-label. The patient and study team will remain blinded until data lock at the end of the study.

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Clazakizumab

Arm Type

Experimental

Arm Description

Clazakizumab - 25mg in 50 milliliters (mL) of 0.9% saline, IV infusion over 30 minutes.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo - 50 mL 0.9% saline, IV infusion over 30 minutes.

Intervention Type

Drug

Intervention Name(s)

Clazakizumab

Intervention Description

Infusion

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Infusion

Primary Outcome Measure Information:

Title

Primary Endpoint

Description

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

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO)

Description

Proportion of participants who need mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) after the first dose of clazakizumab or placebo

Time Frame

14 days

Title

Infusion-related reactions during 24 hours from the time of infusion

Description

Proportion of participants who experience infusion-related reactions during the first 24 hours after infusion of clazakizumab or placebo

Time Frame

24 hours

Title

Patient survival at 28 days

Description

Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo

Time Frame

28 days

Title

Patient survival at 60 days

Description

Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo

Time Frame

60 days

Title

Requirement for open-label clazakizumab

Description

Proportion of participants who require an open-label dose of clazakizumab

Time Frame

14 days

Title

Time in the intensive care unit (ICU)

Description

Number of days in the ICU following the first dose of clazakizumab or placebo

Time Frame

60 days

Title

Time in the hospital

Description

Number of days in the hospital following the first dose of clazakizumab or placebo

Time Frame

60 days

Title

Time to mechanical ventilation

Description

Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation

Time Frame

60 days

Title

Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14

Description

Difference in WHO Clinical Progression Scale between clazakizumab and placebo

Time Frame

14 days

Title

Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28

Description

Difference in WHO Clinical Progression Scale between clazakizumab and placebo

Time Frame

28 days

Title

Change in Radiologic Assessment of Lung Edema (RALE) at day 14

Description

Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 14 from baseline between clazakizumab or placebo

Time Frame

14 days

Title

Change in Radiologic Assessment of Lung Edema (RALE) at day 28

Description

Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 28 from baseline between clazakizumab or placebo

Time Frame

28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Isioma Agboli, MD

Phone

713-441-6311

iagboli@houstonmethodist.org

First Name & Middle Initial & Last Name or Official Title & Degree

Darrel Cleere, BSN

Phone

713-441-6232

dwcleere@houstonmethodist.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Howard Huang, MD

Organizational Affiliation

The Methodist Hospital Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Houston Methodist Hospital

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Isioma Agboli, MD

Phone

713-441-6311

iagboli@houstonmethodist.org

First Name & Middle Initial & Last Name & Degree

Darrel Cleere, BSN

Phone

713-441-6232

dwcleere@houstonmethodist.org

First Name & Middle Initial & Last Name & Degree

Howard J Huang, MD

First Name & Middle Initial & Last Name & Degree

Alex Rogers, PharmD

First Name & Middle Initial & Last Name & Degree

Ahmad Goodarzi, MD

First Name & Middle Initial & Last Name & Degree

Yihad G Youssef, MD

First Name & Middle Initial & Last Name & Degree

Simon Yau, MD

First Name & Middle Initial & Last Name & Degree

Faisal Zahiruddin, MD

First Name & Middle Initial & Last Name & Degree

Linda W Moore, PhD

First Name & Middle Initial & Last Name & Degree

Ahmed O Gaber, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30254251

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.

Results Reference

result

PubMed Identifier

23136551

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.

Results Reference

result

PubMed Identifier

31958792

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.

Results Reference

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PubMed Identifier

32253449

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.

Results Reference

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PubMed Identifier

32181911

Citation

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.

Results Reference

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PubMed Identifier

29622697

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 Aug;23(8):943-947. doi: 10.1634/theoncologist.2018-0028. Epub 2018 Apr 5.

Results Reference

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PubMed Identifier

32192578

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. Epub 2020 Mar 16. No abstract available.

Results Reference

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PubMed Identifier

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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 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/jamainternmed.2020.0994. Erratum In: JAMA Intern Med. 2020 Jul 1;180(7):1031.

Results Reference

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PubMed Identifier

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Citation

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Results Reference

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Clazakizumab vs. Placebo - COVID-19 Infection

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