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Context
mAb114 is a unique monoclonal antibody that targets the receptor binding domain of
Glycoprotein of the Ebola virus, which prevents mortality in rhesus macaques treated after
mortal challenge with
Ebolavirus from Zaire. Here we present accelerated data from HRV 608, a phase 1 study to evaluate mAb114
safety, tolerability, pharmacokinetics and immunogenicity.
The methods
Health Clinic (NIH) (Bethesda, MD, USA), healthy adults ages 18 to 60 years
were sequentially included in three dose groups of mAb114 of 5 mg / kg, 25 mg / kg and
50 mg / kg. The drug was administered to participants intravenously for 30 minutes, and participants
were followed for 24 weeks. Participants were only enrolled at an increased dose
groups after the intermediate safety badessments. Our main evaluation criteria were safety and tolerability,
with pharmacokinetic and anti-drug antibody evaluations as secondary endpoints. we
evaluated the safety and tolerability of all participants who received the drug at the surveillance study
clinical laboratory data and self-badessment and direct badessment by the clinician of the pre-specified
symptoms at the infusion site 3 days after infusion and general symptoms 7 days after infusion.
Unsolicited adverse events were recorded for 28 days. Pharmacokinetics and anti-drugs
Antibody evaluations were performed in participants with at least 56 days of data.
This test is saved with
ClinicalTrials.gov, number
NCT03478891 and is active but no longer recruits.
Results
Between May 16 and September 27, 2018, 19 eligible persons were registered. One (5%)
the participant was not perfused because intravenous access was not adequate. Out of 18 (95%)
remaining participants, three (17%) were badigned to the group receiving 5 mg / kg, five (28%)
group of 25 mg / kg and ten (55%) of the 50 mg / kg group, each receiving
a single infusion of mAb114 at the badigned dose. All infusions were well tolerated
and completed in 30 to 37 minutes without infusion reaction or rate adjustment. All participants
who received the study drug completed the safety badessment of local and systemic agents
reactogenicity. No participants reported symptoms at the infusion site. Systemic symptoms
were all benign and present only in four (22%) of 18 participants, regardless of dosage.
groups. No Unsolicited Adverse Event Related to mAb114 and Serious Adverse Event
event was produced that was not related to mAb114. mAb114 has linear pharmacokinetics and
half-life of 24 · 2 days (standard error of measurement: 0 · 2) without evidence of anti-drugs
antibody development.
Interpretation
mAb114 was well tolerated, exhibited linear pharmacokinetics and was easily and rapidly
infused, making it an attractive and deployable option for treatment in an epidemic situation.
Funding
Vaccine Research Center, National Institute of Allergy and Infectious Diseases,
and NIH.
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