Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
Condition: COVID-19
MeSH terms: COVID-19
Intervention: Clazakizumab; Placebo
Intervention description: Dose is 25mg intravenously over 30 minutes.; Intravenously administered over 30 minutes.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Double (Participant, Investigator)
Masking description: 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.
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Coronavirus; SARS-COVID-2

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.
    

Eligibility criteria:

        Inclusion Criteria:

        In order to be eligible to participate in this study, the patients must meet all of the
        following criteria:

          1. At least 18 years of age

          2. 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.

          3. 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

          4. 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.)

          5. 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:

               1. combined (estrogen and progestogen containing) hormonal contraception combined
                  (estrogen and progestogen containing) hormonal contraception (oral, intravaginal,
                  or transdermal)

               2. progestogen-only hormonal contraception associated with inhibition of ovulation
                  (oral, injectable, implantable)

               3. intrauterine device (IUD)

               4. intrauterine hormone-releasing system (IUS)

               5. vasectomized partner

               6. bilateral tubal occlusion

               7. 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.

          6. 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.

        Exclusion Criteria:

        An individual who meets any of the following criteria will be excluded from participation
        in this study:

          1. Evidence of irreversible injury deemed non-survivable even if the pulmonary failure
             recovers (for example severe anoxic brain injury)

          2. Known active inflammatory bowel disease

          3. Known active, untreated diverticulitis

          4. Known untreated bacteremia

          5. 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).

          6. Known hypersensitivity to the clazakizumab