dMAbs for Prevention of COVID-19

Healthy Volunteers Clinical Trial

Official title: A Phase 1, Open-Label, Single Center, Dose Escalation Study of the Safety and Pharmacokinetics of mAb AZD5396 and mAb AZD8076 Delivered as dMAbs in Healthy Adults

Status Recruiting

Clinical Trial Summary

This is a Phase 1, open-label, single center, dose escalation study to evaluate the safety, tolerability and pharmacokinetic profile of mAb AZD5396 and mAb AZD8076 following delivery of optimized dMAb AZD5396 and dMAb AZD8076 with Hylenex® Recombinant, administered by intramuscular injection (IM) followed immediately by electroporation (EP) using the CELLECTRA® 2000 with Side Port needle device, in a 2-dose regimen (Days 0 and 3) or a 4-dose regimen (Days 0, 3, 28 and 31) in healthy adults.

The hypothesis is that the administration of dMAb AZD5396 and dMAb AZD8076 will be safe and associated with expression of mAb AZD5396 and mAb AZD8076 in serum.

Clinical Trial Description

The study will apply a single ascending dose (SAD) modified 3+3 design. Participants will be enrolled sequentially beginning with Cohort A1. The first participant in cohort A1 will be dosed on Day 0. If no stopping event (DLT) is observed after 14 days of the initial dose, the remaining two participants in that cohort will be dosed. If there are 0 DLT events after 14 days of the initial dosing of the third subject, enrollment will be completed, and then cohort A2 will open. Same process will be followed for Cohorts B, C and E. Because cohorts D, F & G are a similar or lower dose and the safety profile would have been already established in previous cohorts, the 14-day waiting periods will not apply to Cohorts D, F, G or H.

If one dose limiting toxicity (DLT) is observed in the first three participants enrolled in any cohort, an ad hoc DSMB will review the event and make a decision if the study should continue. If the DSMB agrees that the study should continue, the remaining participants will be enrolled in the cohort and dosed, but the next cohort will not open until the 28-day period of safety is completed. However, if any additional DLT occurs (i.e., >1 DLT in 6 total participants in a given cohort), then that dose will be deemed not tolerated

The following Investigational product administration- and/or EP- related adverse events are defined as DLTs:

• Grade 3 or greater local injection site erythema, swelling, and/or induration recorded ≥ 1 hour after Investigational product administration

• Pain or tenderness at the injection site that requires overnight hospitalization despite proper use of non-narcotic analgesics.

• Grade 3 or greater systemic symptoms assessed by the Principal Investigator as related to Investigational product administration.

• Grade 3 or greater clinically significant laboratory abnormalities assessed by the Principal Investigator as related to Investigational product administration. ;

Related Conditions & MeSH terms

• Healthy Volunteers

• NCT number: NCT05293249
• Study type: Interventional
• Source: University of Pennsylvania
• Contact: Pablo Tebas, MD
• Phone: 215-349-8092
• Email: Pablo.Tebas@pennmedicine.upenn.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: May 19, 2022
• Completion date: September 2025