What is the mechanism of action of this treatment?

DNA-encoded monoclonal antibodies (dMAbs) like AZD5396 and AZD8076 are delivered via intramuscular injection followed by electroporation, which enhances cellular uptake of the DNA. Once inside the cells, the DNA instructs the cells to produce the desired antibodies in vivo. This approach is significant for healthy subjects as it enables the body to generate therapeutic antibodies internally, potentially providing a more efficient and sustained immune response compared to traditional methods that rely on external antibody administration.

What side effects are associated with this type of intervention?

Common side effects of monoclonal antibody treatments delivered via intramuscular injection and electroporation include injection site reactions such as pain, redness, and swelling. Systemic side effects may include mild to moderate infections, headache, fatigue, and nasopharyngitis. Severe adverse reactions are less common but can include hypersensitivity reactions and, in rare cases, anaphylaxis.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for DNA-encoded monoclonal antibodies (dMAbs) delivered via intramuscular injection and electroporation in healthy subjects. However, monoclonal antibodies themselves have been widely approved for various conditions, including infectious diseases and cancers. The innovative approach of using dMAbs aims to simplify the production and administration of these therapies by enabling the body to produce the antibodies directly. This method is still under investigation and represents a novel frontier in immunotherapy.

What other types of research exist?

Promising novel alternatives to dMAb AZD5396 and dMAb AZD8076 for healthy subjects in 2024 include: 1) CAR T-cell therapies targeting specific antigens, which have shown efficacy in various cancers and are being explored for infectious diseases. 2) Oncolytic virotherapy, which uses genetically modified viruses to selectively infect and kill cancer cells while stimulating an immune response. 3) Other DNA or RNA-based therapies, such as mRNA vaccines, which have been successful in COVID-19 prevention and are being investigated for other diseases. 4) Bispecific antibodies, which can simultaneously bind to two different antigens, enhancing their therapeutic potential.

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Monoclonal Antibodies

dMAbs for COVID-19 Prevention

Phase 1

Waitlist Available

Led By Pablo Tebas, MD

Research Sponsored by Pablo Tebas

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Screening laboratory must be within normal limits or have only Grade 0-1 findings

No history of clinically significant immunosuppressive or autoimmune disease

Must not have

Chronic liver disease or cirrhosis

Baseline evidence of kidney disease as measured by creatinine greater than 1.5 mg/dL

Timeline

Screening 3 weeks

Treatment Varies

Follow Up immediately after ep, 5 minutes after ep and 10 minutes after ep

Awards & highlights

Summary

This trial tests a new way to deliver disease-fighting proteins using DNA instructions and an electric pulse. It targets healthy adults to ensure safety and tolerability. The treatment helps the body produce its own antibodies by injecting DNA into muscle cells. This technique significantly improves gene expression compared to simple DNA injection.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects may include reactions at the injection site such as pain or swelling, general discomfort like fatigue or headaches due to immune response from dMAb administration. Electroporation might cause temporary skin irritation or muscle twitching.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My recent lab results are mostly normal.

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I do not have a history of serious immune system diseases.

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I am between 18 and 60 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have chronic liver disease or cirrhosis.

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My creatinine level is above 1.5 mg/dL, indicating kidney issues.

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I have diabetes, high blood pressure, asthma, or heart disease that is not well-managed.

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I haven't had a COVID-19 vaccine or plan to get any vaccine within 2 weeks of the last study product dose.

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I am currently on or expect to start immunosuppressive therapy.

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I haven't received any blood products in the last 3 months.

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I have less than two suitable spots for muscle injections.

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I have tattoos or scars near where the treatment will be given.

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I haven't received any antibody treatments in the last 4 weeks.

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I have a condition that weakens my immune system, like a blood cancer or a history of organ transplant.

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I am currently or planning to be treated with TNF-alpha inhibitors.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ immediately after ep, 5 minutes after ep and 10 minutes after ep

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~immediately after ep, 5 minutes after ep and 10 minutes after ep

This trial's timeline: 3 weeks for screening, Varies for treatment, and immediately after ep, 5 minutes after ep and 10 minutes after ep for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Evaluation of laboratory related adverse events

Evaluation of the pain experienced by the participant

Frequency and nature of Serious Adverse Events

+4 more

Trial Design

8Treatment groups

Experimental Treatment

Group I: Cohort G - 4x 0.5 mgExperimental Treatment5 Interventions

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.

Group II: Cohort F - 2x 0.5 mgExperimental Treatment4 Interventions

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.

Group III: Cohort E - 2x 2 mgExperimental Treatment4 Interventions

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.

Group IV: Cohort D - 2x 0.25 mgExperimental Treatment4 Interventions

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.

Group V: Cohort C - 2x 1 mgExperimental Treatment4 Interventions

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.

Group VI: Cohort B - 2x 0.5 mgExperimental Treatment4 Interventions

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.

Group VII: Cohort A2 - 1x 1 mgExperimental Treatment4 Interventions

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.

Group VIII: Cohort A1 - 1x 0.5 mgExperimental Treatment4 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Hylenex

2016

Completed Phase 4

~60

0 / 14Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

DNA-encoded monoclonal antibodies (dMAbs) like AZD5396 and AZD8076 are delivered via intramuscular injection followed by electroporation, which enhances cellular uptake of the DNA. Once inside the cells, the DNA instructs the cells to produce the desired antibodies in vivo. This approach is significant for healthy subjects as it enables the body to generate therapeutic antibodies internally, potentially providing a more efficient and sustained immune response compared to traditional methods that rely on external antibody administration.

[Therapeutic use of a monoclonal, anti-CD4 antibody in refractory rheumatoid polyarthritis. Preliminary results].