dMAbs for Prevention of COVID-19
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
1 other identifier
interventional
61
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 healthy-volunteers
Started May 2022
Longer than P75 for phase_1 healthy-volunteers
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 4, 2022
CompletedFirst Posted
Study publicly available on registry
March 24, 2022
CompletedStudy Start
First participant enrolled
May 19, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 11, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
November 21, 2025
CompletedJanuary 22, 2026
January 1, 2026
3.1 years
March 4, 2022
January 20, 2026
Conditions
Outcome Measures
Primary Outcomes (7)
Frequency and nature of injection site reaction
Injection site reactions occurring up to 7 days after administration of the investigational product
7 days after administration of the investigational products
Frequency and nature of systemic reactions
Systemic reactions occurring up to 7 days after administration of the investigational product.
7 days after administration of the investigational products
Frequency and nature of Serious Adverse Events
SAE will be classified using the CTCAE v5 throughout the study
72 Weeks after administration of the investigational products
Evaluation of the pain experienced by the participant
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.
Immediately after EP, 5 minutes after EP and 10 minutes after EP
Evaluation of laboratory related adverse events
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.
Up to 7 days after administration of the investigational product
Serum concentration of dMAb AZD5396 nm/mL.
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.
Up to 72 Weeks after administration of the investigational products
Serum concentration of dMAb AZD8076 nm/mL.
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.
Up to 72 Weeks after administration of the investigational products
Study Arms (8)
Cohort A1 - 1x 0.5 mg
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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
EXPERIMENTALParticipants (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.
Interventions
Participants will receive one injection of dMAb AZD5396 with Hylenex into the arm (deltoid)/leg (quadriceps) region followed by EP.
Participants will receive one injection of dMAb AZD8076 with Hylenex into the arm (deltoid)/leg (quadriceps) region followed by EP.
Hylenex® recombinant will be used for dMAb AZD5396 and dMAb AZD8076 dose preparation at the clinical site.
The device will be used to perform electroporation (EP) on each subject immediately after being dosed with dMAb AZD5396 and dMAb AZD8076.
The device will be used to perform electroporation (EP) on each subject immediately after being dosed with dMAb AZD5396 and dMAb AZD8076.
Eligibility Criteria
You may qualify if:
- Age 18-60 years.
- Able to provide consent to participate and having signed an Informed Consent Form (ICF).
- Able and willing to comply with all study procedures.
- Body mass index (BMI) between 20 and 31, inclusive.
- Screening laboratory must be within normal limits or have only Grade 0-1 findings.
- Normal screening ECG or screening ECG with no clinically-significant findings.
- Women of child-bearing potential agree to one of the following:
- use medically effective contraception (oral contraception, barrier methods, spermicide, etc.)
- have a partner who is sterile from enrollment to 6 months following the last injection
- have a partner who is medically unable to induce pregnancy Abstinence is acceptable per Investigator discretion and as long as it is documented that the subject will use medically effective contraception when engaging in sexual activities and notifies the study team.
- Sexually active men who are considered sexually fertile must agree to one of the following:
- use a barrier method of contraception during the study and continue its use for at least 6 months following the last injection
- have a partner who is permanently sterile or is medically unable to become pregnant
- No history of clinically significant immunosuppressive or autoimmune disease. Individuals with HIV infection who have been virologically suppressed for more than 1 year and with current CD4 cell count entry greater than 500 cells/ul will be allowed into the study.
You may not qualify if:
- Administration of an investigational compound either currently or within 6 months of first dose.
- Administration of any vaccine within 4 weeks of first dose.
- Administration of a SARS-CoV-2 vaccine in the last 14 days or plans to have any standard of care vaccines within 14 days form the last administration of study products.
- Positive SARS-CoV-2 infection at screening visit.
- Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose.
- Administration of any blood product within 3 months of first dose.
- Co-morbid conditions including poorly-controlled diabetes (HbA1C \> 7), poorly-controlled hypertension (BP \> 140/95 repeatedly), asthma, and any cardiovascular disease.
- Pregnancy or breast feeding or plans to become pregnant during the course of the study.
- Positive serologic test for hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Director.
- Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
- Baseline evidence of kidney disease as measured by creatinine greater than 1.5 mg/dL (CKD Stage II or greater);
- Baseline screening lab with Grade 2 or higher abnormality, except for Grade 2 creatinine.
- Chronic liver disease or cirrhosis.
- Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation.
- Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pablo Tebaslead
- The Wistar Institutecollaborator
- AstraZenecacollaborator
- Inovio Pharmaceuticalscollaborator
Study Sites (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Related Publications (1)
Tebas P, Patel A, Agnes JT, Parzych EM, Baer A, Caturla M, Ghosh S, Purwar M, Bedanova N, Tsang C, Morales K, Amante D, Fisher PD, Francica JR, Humeau L, Kulp DW, Pallesen J, Leon P, Esser M, Smith TRF, Weiner DB. Safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal antibodies in healthy adults: a phase 1 trial. Nat Med. 2025 Dec;31(12):4150-4159. doi: 10.1038/s41591-025-03969-0. Epub 2025 Oct 21.
PMID: 41120767DERIVED
MeSH Terms
Interventions
Study Officials
- PRINCIPAL INVESTIGATOR
Pablo Tebas, MD
University of Pennsylvania
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Professor of Medicine. University of Pennsylvania
Study Record Dates
First Submitted
March 4, 2022
First Posted
March 24, 2022
Study Start
May 19, 2022
Primary Completion
June 11, 2025
Study Completion
November 21, 2025
Last Updated
January 22, 2026
Record last verified: 2026-01