Dosage and administration▾
2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage The recommended dosage of GOHIBIC for the treatment of adults with COVID-19 is 800 mg administered by intravenous infusion after dilution [see Dosage and Administration (2.2) ] for a maximum of 6 (six) doses over the treatment period as described below. Treatment should be started within 48 hours of intubation (Day 1) followed by administration on Days 2, 4, 8, 15 and 22 as long as the patient is hospitalized (even if discharged from ICU). 2.2 Preparation and Administration Preparation Using aseptic technique, dilute and prepare GOHIBIC for intravenous infusion before administration. For the recommended dose of 800 mg GOHIBIC, dilute 80 mL of GOHIBIC in 170 mL of 0.9% Sodium Chloride at room temperature. Use a 250 mL infusion bag of 0.9% Sodium Chloride solution USP and the follow steps below: Withdraw 80 mL of 0.9% Sodium Chloride solution USP from the infusion bag and discard. Withdraw the 80 mL of GOHIBIC from the vials and add slowly to the 0.9% Sodium Chloride solution USP infusion bag to a final concentration of 3.2 mg/mL. To mix the solution, gently invert the bag to avoid foaming. Storage of Diluted GOHIBIC Diluted GOHIBIC must be used within 4 hours when stored at room temperature 20°C to 25°C (68°F to 77°F). Diluted GOHIBIC stored under refrigeration at 2°C to 8°C (36°F to 46°F) must be used within 24 hours. After removal of diluted GOHIBIC from the refrigerator stored at 2°C to 8°C (36°F to 46°F), it must be left to acclimatize to room temperature prior to administration. Administration Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present. Administer diluted GOHIBIC via intravenous infusion over 30 - 60 minutes. Avoid concomitant administration of GOHIBIC with other drugs in the same intravenous line.
Adverse reactions▾
6 ADVERSE REACTIONS 6.1 Clinical Trial Experience The following adverse reactions have been observed in the clinical studies of GOHIBIC that supported the EUA. The adverse reaction rates observed in these clinical studies cannot be directly compared to rates in the clinical studies of other products and may not reflect the rates observed in clinical practice. The safety of GOHIBIC is based on PANAMO, a Phase 3 randomized, placebo-controlled trial in COVID-19 patients requiring IMV or ECMO [see Clinical Studies (14) ] . The analysis of adverse reactions included a total of 364 adult patients who received at least one dose of either GOHIBIC (n=175) or placebo (n=189) plus standard of care. Patients received GOHIBIC 800 mg administered by intravenous infusion on Days 1, 2, 4, 8, 15 and 22 or placebo. During the study, there were 62 deaths in the GOHIBIC arm and 85 deaths in the placebo arm [see Clinical Studies (14) ] . Fatal infections occurred in more placebo patients. Nonfatal serious infections occurred in 58 patients (33.1%) in the GOHIBIC arm and in 55 patients (29.1%) in the placebo arm. The most commonly reported nonfatal serious infections with GOHIBIC were pneumonia (18.9% vs 13.8% in placebo), sepsis (14.9% versus 7.4% in placebo), and septic shock (9.1% versus 7.4% in placebo). Discontinuation of study treatment due to an adverse reaction occurred in 2.9% of the GOHIBIC group and 1.6% of the placebo group. Adverse reactions leading to discontinuation of GOHIBIC included eczema, bronchopulmonary aspergillosis, rash, hemodynamic instability, thrombocytopenia, and multi-organ failure. The most common adverse reactions occurring in at least 3% of GOHIBIC-treated patients and at least 1% more frequently than observed in the placebo arm are summarized in Table 1. Table 1. Adverse Reactions that Occurred in ≥3% of Patients Treated with GOHIBIC and at least 1% More Frequently than Observed in the Placebo Arm through Day 60 Adverse Reactions GOHIBIC + SoC (N=175) Placebo + SoC (N=189) n (%) n (%) SoC = standard of care. A patient is only listed once (regardless of event numbers) but one patient can be listed in different categories with one or additional reactions Pneumonia "Pneumonia" includes preferred terms containing the term "pneumonia"; does not include "COVID-19 pneumonia" 55 (31.4%) 44 (23.3%) Sepsis "Sepsis" includes preferred terms containing the term "sepsis". 38 (21.7%) 30 (15.9%) Delirium "Delirium includes the following preferred terms: Delirium, Intensive care unit delirium 22 (12.6%) 20 10.6%) Pulmonary embolism 19 (10.9%) 17 (9.0%) Hypertension 16 (9.1%) 13 (6.9%) Pneumothorax 14 (8.0%) 11 (5.8%) Deep vein thrombosis 11 (6.3%) 9 (4.8%) Herpes simplex 11 (6.3%) 5 (2.6%) Enterococcal infection 10 (5.7%) 8 (4.2%) Bronchopulmonary aspergillosis 10 (5.7%) 7 (3.7%) Hepatic enzyme increased 9 (5.1%) 7 (3.7%) Urinary tract infection 9 (5.1%) 6 (3.2%) Hypoxia 8 (4.6%) 6 (3.2%) Thrombocytopenia 8 (4.6%) 2 (1.1%) Pneumomediastinum 8 (4.6%) 0 (0.0%) Respiratory tract infection 7 (4.0%) 5 (2.6%) Supraventricular tachycardia 7 (4.0%) 1 (0.5%) Constipation 6 (3.4%) 3 (1.6%) Rash 6 (3.4%) 0 (0.0%) 6.3 Required Reporting for Serious Adverse Events and Medication Errors The prescribing healthcare provider and/or the provider's designee is/are responsible for mandatory reporting of all serious adverse events (SAEs) SAEs are defined as: Death;A life-threatening AE;Inpatient hospitalization or prolongation of existing hospitalization;A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;A congenital anomaly/birth defect;Other important medical event, which may require a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly and medication errors potentially related to GOHIBIC within 7 calendar days from the healthcare provider's awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA requires that such reports, using FDA Form 3500, include the following: Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race) A statement "GOHIBIC use for COVID-19 under Emergency Use Authorization (EUA)" under the " Describe Event, Problem, or Product Use/Medication Error " heading Information about the SAE or medication error ( e.g ., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes). Patient's preexisting medical conditions and use of concomitant products Information about the product ( e.g ., dosage, route of administration, NDC #). Submit AE and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods: Complete and submit the report online: www.fda.gov/medwatch/report.htm Complete and submit a postage-paid FDA Form 3500 (https://www.fda.gov/media/76299/download) and return by: Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or Fax to 1-800-FDA-0178, or Call 1-800-FDA-1088 to request a reporting form In addition, please provide a copy of all FDA MedWatch forms to: InflaRx GmbH Fax: 1-866-728-2630 E-mail: pvusa@inflarx.de Or call InflaRx GmbH at 1-888-254-0602 to report AEs. The prescribing healthcare provider and/or the provider's designee is/are responsible for mandatory responses to requests from FDA for information about AEs and medication errors following receipt of GOHIBIC.
Use in pregnancy▾
8.1 Pregnancy Risk Summary There are no available data on GOHIBIC use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as GOHIBIC is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In an enhanced pre- and post-natal (ePPND) study conducted in cynomolgus monkeys, placental transport of GOHIBIC was observed but there was no evidence of fetal harm following intravenous administration of GOHIBIC throughout pregnancy at doses 2.5 times the maximum recommended human dose (MRHD) of 800 mg on a mg/kg basis (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in clinical recognized pregnancies is 2% - 4% and 15% - 20%, respectively. Data Animal Data In the ePPND study, pregnant cynomolgus monkeys received GOHIBIC from GD20 to GD22 (dependent on pregnancy determination), at the beginning of organogenesis, and once every 7 days until the end of gestation at intravenous doses up to 50.6 mg/kg/wk (2.5 times the MRHD on a mg/kg basis). There were no GOHIBIC-related adverse effects on maternal health, pregnancy outcome, embryo-fetal development, or neonatal growth and development up to 6 months of age (PND183). GOHIBIC crossed the placenta in cynomolgus monkeys and GOHIBIC plasma concentrations were similar in infants relative to maternal animals on PND28 and were 8-12 times higher in infants relative to maternal animals on PND91. GOHIBIC was not detected in infant plasma on PND183.