Clazakizumab vs. Placebo - COVID-19 Infection

NCT04494724 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: Pro00025969
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19 Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

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

  14 days

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

  24 hours

• Patient survival at 28 days

  28 days

• Patient survival at 60 days

  60 days

• Requirement for open-label clazakizumab

  14 days

Study Arms (2)

Clazakizumab

EXPERIMENTAL

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

Drug: Clazakizumab

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Clazakizumab DRUG

Infusion

Clazakizumab

Placebo DRUG

Infusion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (9)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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.

  PMID: 32167524 RESULT

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Respiratory Aspiration; Respiratory Distress Syndrome

Interventions

clazakizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Howard Huang, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isioma Agboli, MD

CONTACT

713-441-6311; iagboli@houstonmethodist.org

Darrel Cleere, BSN

CONTACT

713-441-6232; dwcleere@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: July 31, 2020
• Study Start: July 13, 2020
• Primary Completion: December 31, 2020
• Study Completion: July 31, 2021
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)