dMAbs for Prevention of COVID-19
- Conditions
- Healthy Volunteers
- Interventions
- Combination Product: dMAb AZD5396Combination Product: dMAb AZD8076Combination Product: CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation deviceCombination Product: CELLECTRA™ 2000 with Side Port needle, OpBlock 0070 Electroporation device
- Registration Number
- NCT05293249
- Lead Sponsor
- Pablo Tebas
- Brief 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.
- Detailed 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 or G.
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 61
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort A1 - 1x 0.5 mg dMAb AZD5396 Participants (n=3) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 0.5 mg of each plasmid. Cohort B - 2x 0.5 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=6) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort A2 - 1x 1 mg dMAb AZD5396 Participants (n=3) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 1 mg of each plasmid. Cohort A2 - 1x 1 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=3) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 1 mg of each plasmid. Cohort B - 2x 0.5 mg dMAb AZD8076 Participants (n=6) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort E - 2x 2 mg dMAb AZD8076 Participants (n=5) will be administered 2 mg of dMAb AZD5396 and 2 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 4 mg of each plasmid. Cohort E - 2x 2 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=5) will be administered 2 mg of dMAb AZD5396 and 2 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 4 mg of each plasmid. Cohort B - 2x 0.5 mg dMAb AZD5396 Participants (n=6) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort C - 2x 1 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=6) will be administered 1mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort E - 2x 2 mg dMAb AZD5396 Participants (n=5) will be administered 2 mg of dMAb AZD5396 and 2 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 4 mg of each plasmid. Cohort F - 2x 0.5 mg dMAb AZD8076 Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0070 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort D - 2x 0.25 mg dMAb AZD5396 Participants (n=6) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort A1 - 1x 0.5 mg dMAb AZD8076 Participants (n=3) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 0.5 mg of each plasmid. Cohort A1 - 1x 0.5 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=3) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 0.5 mg of each plasmid. Cohort A2 - 1x 1 mg dMAb AZD8076 Participants (n=3) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 1 mg of each plasmid. Cohort D - 2x 0.25 mg dMAb AZD8076 Participants (n=6) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort F - 2x 0.5 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0070 Electroporation device Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0070 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort C - 2x 1 mg dMAb AZD5396 Participants (n=6) will be administered 1mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort D - 2x 0.25 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=6) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort F - 2x 0.5 mg dMAb AZD5396 Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0070 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort G - 4x 0.5 mg dMAb AZD5396 Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, D3, D28 and D31, for a total dose of 2 mg of each plasmid. Cohort C - 2x 1 mg dMAb AZD8076 Participants (n=6) will be administered 1mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort G - 4x 0.5 mg dMAb AZD8076 Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, D3, D28 and D31, for a total dose of 2 mg of each plasmid. Cohort G - 4x 0.5 mg CELLECTRA™ 2000 with Side Port needle, OpBlock 0078 Electroporation device Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, D3, D28 and D31, for a total dose of 2 mg of each plasmid. Cohort G - 4x 0.5 mg Hylenex Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, D3, D28 and D31, for a total dose of 2 mg of each plasmid. Cohort A2 - 1x 1 mg Hylenex Participants (n=3) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 1 mg of each plasmid. Cohort A1 - 1x 0.5 mg Hylenex Participants (n=3) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0, for a total dose of 0.5 mg of each plasmid. Cohort B - 2x 0.5 mg Hylenex Participants (n=6) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 1 mg of each plasmid. Cohort C - 2x 1 mg Hylenex Participants (n=6) will be administered 1mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort D - 2x 0.25 mg Hylenex Participants (n=6) will be administered 1 mg of dMAb AZD5396 and 1 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 2 mg of each plasmid. Cohort E - 2x 2 mg Hylenex Participants (n=5) will be administered 2 mg of dMAb AZD5396 and 2 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0078 parameter on D0 and D3, for a total dose of 4 mg of each plasmid. Cohort F - 2x 0.5 mg Hylenex Participants (n=5) will be administered 0.5 mg of dMAb AZD5396 and 0.5 mg of dMAb AZD8076 with Hylenex® delivered intramuscularly using the side port needle followed by electroporation (EP) with OpBlock 0070 parameter on D0 and D3, for a total dose of 1 mg of each plasmid.
- Primary Outcome Measures
Name Time Method Evaluation of the pain experienced by the participant Immediately after EP, 5 minutes after EP and 10 minutes after EP Visual analogue scale (VAS). A VAS consists of a horizontal line, 10 cm in length, anchored by word descriptors at each end (no pain = 0 cm; worst pain = 10 cm). The VAS score is determined by measuring in centimeters from the left hand end of the line to the point that the patient marks. Absolute initial value and change over time will be described.
Serum concentration of dMAb AZD5396 nm/mL. Up to 72 Weeks after administration of the investigational products The number and percentage of participants in which detection of monoclonal antibody dMAb AZD5396 in serum is achieved will be summarized with a point estimate and corresponding exact 90% Clopper- Pearson confidence interval. These will be summarized per time point within each cohort. We will also estimate the time to 50% decline from peak concentration.
Frequency and nature of injection site reaction 7 days after administration of the investigational products Injection site reactions occurring up to 7 days after administration of the investigational product
Serum concentration of dMAb AZD8076 nm/mL. Up to 72 Weeks after administration of the investigational products The number and percentage of participants in which detection of monoclonal antibody dMAb AZD8076 in serum is achieved will be summarized with a point estimate and corresponding exact 90% Clopper- Pearson confidence interval. These will be summarized per time point within each cohort. We will also estimate the time to 50% decline from peak concentration.
Frequency and nature of Serious Adverse Events 72 Weeks after administration of the investigational products SAE will be classified using the CTCAE v5 throughout the study
Evaluation of laboratory related adverse events Up to 7 days after administration of the investigational product Laboratory AEs will be assessed and graded in accordance with the "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials", issued in September 2007.
Frequency and nature of systemic reactions 7 days after administration of the investigational products Systemic reactions occurring up to 7 days after administration of the investigational product.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States