dMAbs for COVID-19 Prevention

AB
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Pablo Tebas, MD profile photo
Overseen ByPablo Tebas, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of two new treatments, dMAb AZD5396 and dMAb AZD8076, designed to help prevent COVID-19. It examines how well these treatments are tolerated and how they behave in the body at different doses. The study involves healthy adults who haven't received recent vaccines or had COVID-19 and are free of serious health issues like uncontrolled diabetes or heart disease. Participants must be comfortable with injections and adhere closely to study procedures.

As a Phase 1 trial, participants will be among the first to receive these new treatments, aiding researchers in understanding how they work in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like blood thinners or immunosuppressive therapies. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both dMAb AZD5396 and dMAb AZD8076 were generally well-tolerated in earlier studies. Most participants experienced only mild side effects, localized to the treatment area. Importantly, about 1,000 blood samples revealed no anti-drug antibodies, suggesting a low risk of adverse reactions to the treatment.

Additionally, these DNA-encoded monoclonal antibodies (DMAbs) appeared in the bloodstream of all participants tested in past trials, with no major safety concerns reported. This is encouraging for those considering joining a trial, as the treatment demonstrated a good safety profile in previous research.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about dMAbs AZD5396 and AZD8076 for COVID-19 prevention because they represent a novel approach using DNA-based antibodies. Unlike traditional vaccines or antiviral drugs, which stimulate the immune system or directly attack the virus, these dMAbs introduce DNA sequences that instruct the body to produce antibodies against the virus, providing a potentially faster and more adaptable response. Additionally, the use of electroporation — a technique that enhances the uptake of DNA into cells — could improve the efficiency and effectiveness of antibody production. This innovative delivery method sets these treatments apart, potentially offering a more rapid protective effect than existing options.

What evidence suggests that this trial's treatments could be effective for COVID-19 prevention?

Research has shown that dMAb AZD5396 and dMAb AZD8076, both under study in this trial, are designed to help the body produce antibodies against COVID-19. In earlier studies, these treatments maintained stable antibody levels in participants for up to 72 weeks, suggesting long-lasting antibodies that might offer extended protection against the virus. These treatments are based on successful monoclonal antibodies but use a DNA method to instruct the body to produce them. Initial results appear promising, but further information is needed to fully confirm their effectiveness.16789

Who Is on the Research Team?

Pablo Tebas, MD profile | PennMedicine.org

Pablo Tebas, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Healthy adults aged 18-60 with a BMI of 20-30, normal ECG and lab results, willing to use contraception if fertile. Excludes those with SARS-CoV-2 infection, recent antibody treatments or vaccines, pregnancy, certain infections like hepatitis B/C, immunosuppressive conditions or medications, major surgery within the last 6 months, metal implants at EP site.

Inclusion Criteria

Normal screening ECG or screening ECG with no clinically-significant findings
My recent lab results are mostly normal.
For Cohort H: Participants in a prior cohort who received their first dose at least 52 weeks prior to Cohort H Day 0 dose
See 7 more

Exclusion Criteria

Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD)
I have chronic liver disease or cirrhosis.
Baseline screening lab with Grade 2 or higher abnormality, except for Grade 2 creatinine
See 26 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dMAb AZD5396 and dMAb AZD8076 with Hylenex® delivered intramuscularly followed by electroporation in a 2-dose or 4-dose regimen

4 weeks
4 visits (in-person) for 4-dose regimen, 2 visits (in-person) for 2-dose regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

72 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • dMAb AZD5396
  • dMAb AZD8076
Trial Overview The trial is testing two dMAbs (AZD5396 and AZD8076) for COVID-19 prevention in healthy adults. Participants will receive intramuscular injections followed by electroporation using CELLECTRA devices on Days 0 and 3. The study aims to assess safety and how the body processes these antibodies.
How Is the Trial Designed?
8Treatment groups
Experimental Treatment
Group I: Cohort G - 4x 0.5 mgExperimental Treatment5 Interventions
Group II: Cohort F - 2x 0.5 mgExperimental Treatment4 Interventions
Group III: Cohort E - 2x 2 mgExperimental Treatment4 Interventions
Group IV: Cohort D - 2x 0.25 mgExperimental Treatment4 Interventions
Group V: Cohort C - 2x 1 mgExperimental Treatment4 Interventions
Group VI: Cohort B - 2x 0.5 mgExperimental Treatment4 Interventions
Group VII: Cohort A2 - 1x 1 mgExperimental Treatment4 Interventions
Group VIII: Cohort A1 - 1x 0.5 mgExperimental Treatment4 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Pablo Tebas

Lead Sponsor

Trials
1
Recruited
60+

The Wistar Institute

Collaborator

Trials
10
Recruited
790+

AstraZeneca

Industry Sponsor

Trials
4,491
Recruited
290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Inovio Pharmaceuticals

Industry Sponsor

Trials
54
Recruited
4,800+

Citations

Safety and pharmacokinetics of SARS-CoV-2 DNA- ...Optimized DMAb constructs were developed in response to the COVID-19 pandemic, encoding AZD5396 and AZD8076, which are based on the parental mAb ...
News Details - Investors & Media - INOVIO PharmaceuticalsLong-lasting in vivo antibody production: DMAb levels remained stable for 72 weeks in all participants (n=24) who have reached that ...
INOVIO Announces Promising Interim Results from ...Long-lasting in vivo antibody production: DMAb levels remained stable for 72 weeks in all participants (n=24) who have reached that ...
Nucleic acid-encoded antibody gene transfer-next generation ...This study aims to evaluate the DMAb forms (DMAb AZD5396 and DMAb ... Serious adverse events of special interest following mRNA COVID-19 ...
ICF_000.pdfSerious (but rare) hypersensitivity reactions, including anaphylaxis, have been observed when using monoclonal antibodies similar to dMAb AZD5396 and dMAb ...
Clinical Proof-of-Concept Data for DNA-Encoded Monoclonal ...The primary endpoints were safety and pharmacokinetics. DMAbs were detected in 100% of evaluable participants (n=39), with serum concentrations ...
NCT05293249 | dMAbs for Prevention of COVID-19The 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.
INO) publishes Nature Medicine DMAb dataSafety signals were mild and local, and investigators found no anti‑drug antibodies across ~1,000 blood samples, an uncommon and notable outcome ...
(PDF) Safety and pharmacokinetics of SARS-CoV-2 DNA ...... DMAb levels (Extended Data ... Conclusions: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns.
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