NCT04363502
Trial name or title	Use of the interleukin‐6 inhibitor clazakizumab in patients with life‐threatening COVID‐19 infection
Methods	RCT, placebo‐controlled, double‐blind study Date of study: April 2020 Location: USA Phase 2
Participants	Randomised: 30 participants Inclusion criteria At least 18 years of age ·Confirmed COVID‐19 disease (by Cobas severe acute respiratory syndrome (SARS)‐CoV‐2 real time RT‐PCR using nasopharyngeal swab sample, or equivalent test available to be performed by the Johns Hopkins Medical Laboratories Services). Effort will be made to have the confirmatory test result < 72 hours prior to enrolment 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 SpO2 < 90% on 4L (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; 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 1 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 (oestrogen and progestogen containing) hormonal contraception combined (oestrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal); progestogen‐only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); IUD; IUS; vasectomised partner; bilateral tubal occlusion; true abstinence. when this is in line with the preferred and usual lifestyle of the participant. 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 enrolment until at 5 months after the last dose of study drug, if not abstinent Exclusion criteria 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 bacteraemia Pregnancy. (The protocol will exclude pregnant participants 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 participants be excluded on this basis). Known hypersensitivity to the clazakizumab Use of other IL‐6 inhibitor investigational drugs at the time of enrolment
Interventions	Intervention: clazakizumab (IV, 25 mg, if the CRP does not decrease by 50% within 36 to 48 hours after the 1st dose, a 2nd dose of 25 mg clazakizumab will be given no later than day 3) Control interventions: placebo
Outcomes	Primary outcome Secondary outcomes
Starting date	Study start date: 7 May 2020
Contact information	Johns Hopkins University, Nada Alachkar, MD, 4106149225, nalachk1@jhmi.edu
Notes	Ongoing