Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

NCT04381052 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAT0142
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.

Conditions

COVID-19

Keywords

Coronavirus; SARS-COVID-2

Outcome Measures

Primary Outcomes (1)

• Cumulative Incidence of Serious Adverse Events Associated With Clazakizumab or Placebo

  60 days

Secondary Outcomes (12)

• Cumulative Incidence of Intubation

  14 days

• Time to Extubation

  14 days

• Length of Intensive Care Unit (ICU) Stay

  14 days

• Number of Patients Who Present a Decrease in C-reactive Protein (CRP)

  14 days

• Number of Patients With Acute Kidney Injury (AKI)

  14 days

Study Arms (2)

Clazakizumab 25 mg

EXPERIMENTAL

The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Clazakizumab 25 mg arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum C-reactive protein (CRP) will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of 25 mg clazakizumab will be given no later than day 3.

Drug: Clazakizumab

Placebo

PLACEBO COMPARATOR

The first dose will be administered as soon as possible after the patient is enrolled and randomized into the Placebo arm. The route of administration will be intravenous. Each dose will be administered as an infusion that is run over 30 minutes. Serum CRP will be evaluated at baseline and on days 1 and 2 following clazakizumab administration. If the CRP does not decrease by 50% within 36-48 hours after the first dose, a second dose of placebo will be given no later than day 3.

Other: Placebo

Interventions

Clazakizumab DRUG

Dose is 25mg intravenously over 30 minutes.

Also known as: Clazakizumab solution

Clazakizumab 25 mg

Placebo OTHER

Intravenously administered over 30 minutes.

Placebo

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, the patients must meet all of the following criteria:
• At least 18 years of age
• Confirmed COVID-19 disease (by Cobas SARS-CoV-2 real time reverse transcription polymerase chain reaction (RT-PCR) using nasopharyngeal swab sample, or equivalent test available to be performed by the Columbia University Irving Medical Center (CUIMC)/New York Presbyterian (NYP) clinical laboratory). Effort will be made to have the confirmatory test result \<72 hours prior to enrollment however given overall clinical demand this may not be feasible in all cases.
• Respiratory failure manifesting as: Acute Respiratory Distress Syndrome (defined by a P/F ratio of \<200), OR oxygen saturation (SpO2) \< 90% on 4 liters (L) (actual or expected given higher O2 requirement) OR increasing O2 requirements over 24 hours, plus 2 or more of the following predictors for severe disease:
• CRP \> 35 mg/L Ferritin \> 500 ng/mL D-dimer \> 1 mcg/L Neutrophil-Lymphocyte Ratio \> 4 Lactate dehydrogenase (LDH) \> 200 U/L Increase in troponin in patient w/out known cardiac disease
• Has a consent designee willing to provide informed consent on behalf of the patient (this assumes that a mechanically ventilated patients lacks capacity to consent on his/her own behalf. Should it be deemed that the patient has capacity to consent, consent may be obtained from the patient.)
• Women of childbearing potential must be willing and able to use at least one highly effective contraceptive method for a period of 5 months following the study drug administration. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
• combined (estrogen and progestogen containing) hormonal contraception combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal)
• progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• vasectomized partner
• bilateral tubal occlusion
• true abstinence. when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence, such as calendar, ovulation, symptothermal, postovulation methods, and withdrawal are not acceptable methods of contraception.
• Men must be willing to use a double-barrier contraception from enrollment until at 5 months after the last dose of study drug, if not abstinent.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Evidence of irreversible injury deemed non-survivable even if the pulmonary failure recovers (for example severe anoxic brain injury)
• Known active inflammatory bowel disease
• Known active, untreated diverticulitis
• Known untreated bacteremia
• Pregnancy. (The protocol will exclude pregnant subjects given the lack of overall data on use of clazakizumab in pregnancy however the study team would consider a protocol revision should more than 3 potential pregnant study subjects be excluded on this basis).
• Known hypersensitivity to the clazakizumab

Sponsors & Collaborators

• Columbia University: lead
• NYU Langone Health: collaborator
• CSL Behring: collaborator

Study Sites (1)

Columbia University Medical Center / New York Presbyerian Hospital

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

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

Limitations and Caveats

Study was closed due to no further development. Data was not analyzed or disclosed due to subject confidentiality being an issue (n=1). Assignment was not unblinded/disclosed.

Results Point of Contact

• Title: David J. Cohen, MD
• Organization: Columbia University

djc5@cumc.columbia.edu

212-305-3273

Study Officials

• David J. Cohen, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study is double-blind and therefore neither the Investigator, the subject, the Sponsor and its representatives, nor other designated study site personnel involved in running of the study will be aware of the identification of the investigational drug administered to each subject.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind, placebo-controlled, adaptive seamless Phase II/III design (ASD). The investigators propose the administration of an investigational drug in patients with high predicted short-term mortality secondary to COVID-19 disease. Patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 8, 2020
• Study Start: May 18, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: April 8, 2022
• Results First Posted: April 8, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)