6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice. Overall, 424 adult and pediatric participants with Orthoebolavirus zairense infection received EBANGA in one clinical trial and as part of an expanded access program during the 2018 Orthoebolavirus zairense outbreak in the Democratic Republic of Congo (DRC).
In the PALM trial, the safety of EBANGA was evaluated in a multi-center, open-label, randomized controlled trial, in which 173 participants (119 adults and 54 pediatric participants) with confirmed Orthoebolavirus zairense infection received EBANGA as a single 50 mg/kg IV infusion and 168 participants received an investigational control [see Clinical Studies (14) ] . All participants received optimized standard of care treatment (oSOC).
The median age of the study population that received EBANGA was 26 years (range: 1 day to 85 years) and 55% were female. During the same outbreak, 251 participants (173 adults and 78 pediatric participants) with laboratory-confirmed Orthoebolavirus zairense infection received EBANGA under an expanded access program, 57% of whom were female. Ages ranged from 6 days to 80 years, with a median age of 25 years. Common Adverse Events Table 2 summarizes the adverse events that were reported in the PALM trial from a pre-defined list of signs and symptoms that occurred during EBANGA infusion.
The evaluation of adverse events in participants who received EBANGA may have been confounded by the signs and symptoms of the underlying Orthoebolavirus zairense infection. Twenty nine percent (n=51) of participants who received EBANGA in the PALM Trial experienced a pre-specified infusion-related adverse event. The most common pre-specified infusion-related adverse event reported in at least 10% of participants who received EBANGA was fever ( Table 2 ).
The adverse event profile in adult and pediatric participants treated with EBANGA was similar. Table 2 Adverse Events That Occurred During Infusion in >10% of Adult and Pediatric Participants in the PALM Trial Adverse Event a EBANGA (N=173) % Control b (N=168) % a Adverse events in this table were reported on the day of infusion, and included signs and symptoms that occurred during or immediately after infusion b Investigational therapy administered as three separate infusions c Adverse events that occurred during infusion but were not pre-specified. d The term chills includes other similar adverse events including rigors and tremors Pyrexia 17 58 Tachycardia 9 32 Diarrhea c 9 18 Vomiting c 8 23 Hypotension 8 31 Tachypnea 6 28 Chills d 5 33 Hypoxia c 3 11 The following pre-specified symptoms, which were assessed on a daily basis during admission while admitted to the treatment unit, were reported in ≥40% of participants who received EBANGA: diarrhea, pyrexia, abdominal pain, and vomiting.
Evaluation of these symptoms may have been confounded by the underlying Orthoebolavirus zairense infection. Discontinuation and Infusion Rate Adjustments Approximately 99% of participants who received EBANGA in the PALM trial were able to complete their dose within one hour. Two participants who received EBANGA (1%) did not receive their complete infusion. In eight participants (5%) the EBANGA infusion rate was decreased due to an AE [see Warnings and Precautions (5.1) ] .
Selected Laboratory Abnormalities in the PALM Trial Table 3 presents selected laboratory abnormalities (worsening to Grade 3 or 4 compared to baseline) in the PALM trial. Table 3 Selected Grade 3 and 4 Laboratory Abnormalities a , Worsened Grade from Baseline in the PALM Trial ULN= upper limit of normal a Graded per Division of AIDS (DAIDS) v2.1 b Based on a ULN of 1.2 mg/dL. c Based on a ULN of 47 U/L. d Based on a ULN of 38 U/L.
Laboratory Test a EBANGA N=173 % Control N=168 % Sodium, high ≥ 154 mmol/L 5 4 Sodium, low < 125 mmol/L 7 11 Potassium, high ≥ 6.5 mmol/L 15 12 Potassium, low < 2.5 mmol/L 6 8 Creatinine (mg/dL) > 1.8 × ULN or ≥ 1.5 × baseline b 27 23 Alanine aminotransferase (U/L) ≥ 5 × ULN c 12 14 Aspartate aminotransferase (U/L) ≥ 5 × ULN d 13 18
