Covid-19 living Data

Vilobelimab vs Placebo/Standard care (RCT)

Hospitalized patients

FOREST PLOTS -2022-10-14

Studies description

Trial NCT04333420, EudraCT 2020-001335-28
Publication PANAMO - Vlaar APJ, Lancet Respir Med (2022) (published paper)
Dates: 2020-10-01 to 2021-10-04
Funding: Mixed (This trial was funded by InflaRx and partly funded by the German Federal Government. The funder of the study had a role in study design, data collection, data analysis, data interpretation, and writing of the report.)
Conflict of interest: Yes

Methods
	RCT Blinding: triple blinding
	Location : Multicenter / Netherlands (37%), Brazil (20%), Mexico (10%), France (9%), Russia (6%), Germany (6%), Belgium (4%), Peru (4%), and South Africa (3%) Follow-up duration (days): 60
Inclusion criteria	Aged 18 years or older Were receiving invasive mechanical ventilation within 48 h before the first infusion of study medication Had a PaO2/FiO2 ratio of 60–200 mm Hg Confirmed SARS-CoV-2 infection in the past 14 days
Exclusion criteria	Invasive mechanical ventilation for more than 48 h at the first infusion of study medication Expected stop of invasive ventilation or extubation within the next 24 h History of renal replacement therapy 14 days before random assignment Severe chronic obstructive pulmonary disease Not approved or investigational treatment in the past 7 days Cytokine adsorption therapy in the past 3 days Known hypersensitivity to vilobelimab Pregnancy Organ or bone marrow transplant in past 3 months Cardiopulmonary mechanical resuscitation in the past 14 days Anticancer therapy for haemato-oncological disease in the past 4 weeks Active malignant disease Severe congestive heart failure Chronic liver disease A moribund state Expected death within 24 h of random assignment Participating in or has participated in other investigational interventional studies (drug or device) within the last 7 days before randomization
Interventions
	Treatment Vilobelimab 800 mg IV for a maximum of 6 doses, as one dose per day on days 1, 2, 4, 8, 15, and 22
	Control Placebo
Participants
	Randomized participants : Vilobelimab=178 Placebo=191
	Characteristics of participants N= 369 Mean age : NR 252 males Severity : Mild: n=0 / Moderate: n=0 / Severe: n=0 Critical: n=369
Primary outcome
	In the register Mortality [Time Frame: Day 28]: 28-day all-cause mortality
	In the report All-cause mortality at 28 days in the full analysis set
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: N
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published article and its supplement, the protocol, SAP and study registry were used in data extraction and risk of bias assessment. The study (N=369) achieved the target sample size specified in the trial registry. There is no change from the trial registration in the intervention and control treatments. The registry primary outcome reflects the reported primary outcome. Adverse and serious adverse events were classified as "treatment-emergent" in the report.

Trial NCT04333420
Publication PANAMO - Vlaar APJ, Lancet Rheumatol (2020) (published paper)
Dates: 2020-03-31 to 2020-04-24
Funding: Private (InflaRx GmbH)
Conflict of interest: Yes

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / The Netherlands Follow-up duration (days): 28
Inclusion criteria	age 18 years or older severe pneumonia with pulmonary infiltrates consistent with pneumonia, a clinical history of severe shortness of breath within the past 14 days, or a need for non-invasive or invasive ventilation severe disease defined as a ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) between 100 mm Hg and 250 mm Hg in the supine position and SARS-CoV-2 infection confirmed by RT-PCR.
Exclusion criteria	Invasive mechanical ventilation for more than 48 h improvement in PaO2/FiO2 of more than 30% in the past 24 h known history of progressed chronic obstructive pulmonary disease (COPD Global Initiative for Chronic Obstructive Lung Disease [GOLD] group C or D) severe congestive heart failure (New York Heart Association class III or IV) known pregnancy chronic dialysis, cancer, or other lifelimiting disease with life expectancy less than 6 months renal replacement therapy cardiac resuscitation in the past 14 days organ or bone marrow transplantation in the past 3 months anticancer therapy for oncological disease in the past 4 weeks corticosteroid treatment equivalent to 10 mg prednisone or more per day treatment with other biological therapy for COVID-19 in the past 14 days or use of viral replication inhibitor in the past 3 days. Patients who were near death or expected to die within 12 h or with hypersensitivity to IFX-1 were also excluded.
Interventions
	Treatment Vilobelimab 800 mg IV on days 1, 2, 4, 8 and 15. Two additional doses could be administered (one between days 11 and 13, one at day 22) depending on the patient's condition.
	Control Standard care
Participants
	Randomized participants : Standard care=15 Vilobelimab=15
	Characteristics of participants N= 30 Mean age : NR 22 males Severity : Mild: n=0 / Moderate: n=4 / Severe: n=8 Critical: n=18
Primary outcome
	In the register Change in PaO2/FiO2 [ Time Frame: Baseline to Day 5 ] Relative change (%) from baseline in Oxygenation Index (PaO2 / FiO2) to day 5.
	In the report percentage change in PaO2/FiO2 in the supine position from baseline (day 1, before study drug administration and within 1 h before or after randomisation) to day 5
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: N
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to all available versions of the published/preprint article, the study registry was used in data extraction and risk of bias assessment. This report is based on the results of a phase II trial; the sample size specified in the registry was not used "This was planned to inform the choice of endpoints and study population specifications for a potential phase 3 part of the study. For phase 2, we pragmatically set the sample size to 30 patients". There is no change from the trial registration in the intervention and control treatments. There is no change from the trial registration in the primary outcome however, mortality was not an outcome listed in the trial registry. Authors state in the discussion the limitations of the primary outcome reporting in the trial registry and say that even though it did not show a difference, treatment showed a lower rate in mortality, "which is consistent with a potential treatment benefit of IFX-1". Serious adverse events and total averse events were also not listed in registry. The study was funded by the drug company who made the drug, and they were also part of the authorship team.