Phase 2
N=178
A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection
COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT04343989 ↗Enrolled (actual)
178
Serious AEs
35.4%
Results posted
Feb 2022
Primary outcome: Primary: Ventilator Free Survival — 58; 19; 44 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Clazakizumab 25 mg (Drug); Clazakizumab 12.5 mg (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- NYU Langone Health
- Primary completion
- Feb 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Ventilator Free Survival |
58; 19; 44 | — |
| PRIMARY Number of Serious Adverse Events Associated With High and Low Dose of Clazakizumab |
46; 6; 51 | — |
| SECONDARY Overall Patient Survival |
56; 20; 46 | — |
| SECONDARY Overall Patient Survival |
56; 20; 46 | — |
| SECONDARY Number of Participants With Change in Clinical Status |
50; 15; 37 | — |
| SECONDARY Number of Participants With a Change in Clinical Status |
54; 17; 40 | — |
| SECONDARY Number of Clazakizumab-expected Adverse Events |
7; 3; 12 | — |
Summary
In this study invetigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a double-blinded randomized multi-center trial designed as a phase II dose-finding three arm trial with seamless adaptive transition to a phase III efficacy trial. For phase II, patients were randomized 1:1:1 ratio to three study arms and received clazakizumab at a dose of 12.5 mg, 25 mg or placebo.
Based on interim analysis, the low dose arm was dropped and the phase III portion of the study continued to enroll patients randomized 1:1 to high dose clazakizumab or placebo.
Based on interim analysis, the remaining 10 subjects at NYU will be randomly assigned to a 1:1 ratio to two arms that will receive clazakizumab at a dose of 25 mg or placebo. The NYU site will serve as the central data management site for other centers who undertake this protocol. Other sites will enroll patients based on the two arm 1:1 randomization. 60 patients at outside sites are expected to enroll.
Eligibility Criteria
Inclusion Criteria
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 RT-PCR using nasopharyngeal swab sample, or equivalent test available to be performed by the NYU Langone clinical laboratory). Effort will be made to have the confirmatory test result 35 mg/L Ferritin > 500 ng/mL D-dimer > 1000 mg/mL 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 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.
Exclusion Criteria
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
Data sourced from ClinicalTrials.gov (NCT04343989). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.