dMAbs for Prevention of COVID-19

• Status: Not yet recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1, open-label, single center, dose escalation study to evaluate the safety 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) 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Pablo Tebas
• Collaborators: AstraZeneca; Inovio Pharmaceuticals; The Wistar Institute; United States Department of Defense
• Treatments: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion Criteria:

1. Age 18-60 years;

2. Able to provide consent to participate and having signed an Informed Consent Form (ICF);

3. Able and willing to comply with all study procedures;

4. Body mass index (BMI) between 20 and 30, inclusive

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

6. Normal screening ECG or screening ECG with no clinically significant findings;

7. Women of child-bearing potential agree to use medically effective contraception (oral contraception, barrier methods, spermicide, etc.) or have a partner who is sterile from enrollment to 6 months following the last injection or 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.

8. Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception during the study, and agree to continue the use for at least 6 months following the last injection, or have a partner who is permanently sterile or is medically unable to become pregnant;

9. 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.

Exclusion Criteria:

1. Administration of an investigational compound either currently or within 30 days of first dose;

2. Administration of any vaccine within 4 weeks of first dose;

3. Administration of a SARS-CoV-2 vaccine in the last 90 days

4. Positive SARS-CoV-2 infection at screening visit.

5. Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose

6. Administration of any blood product within 3 months of first dose;

7. Pregnancy or breast feeding or plans to become pregnant during the course of the study;

8. Positive serologic test for hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Director;

9. Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);

10. Baseline evidence of kidney disease as measured by creatinine greater than 1.5 mg/dL (CKD Stage II or greater);

11. Baseline screening lab with Grade 2 or higher abnormality, except for Grade 2 creatinine;

12. Chronic liver disease or cirrhosis

13. Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation;

14. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or prednisone at a dose greater than 10 mg/day or steroid dose-equivalent);

15. Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept;

16. Prior major surgery or any radiation therapy within 4 weeks of first dose

17. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;

18. Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator (AICD)

19. Fewer than two acceptable sites available for IM injection and EP considering the deltoid and anterolateral quadriceps muscles. The following are unacceptable sites:

1. Tattoos, keloids or hypertrophic scars located within 2 cm of intended administration site;

2. Implantable-Cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the deltoid injection site (unless deemed acceptable by a cardiologist);

3. Any metal implants or implantable medical device within the electroporation site.

20. Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness;

21. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints;

22. Not willing to allow storage and future use of samples for SARS-CoV-2 virus related research

23. Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint.

24. Participants with known bleeding diatheses or that are using blood thinners for 30 days before study enrollment including warfarin, heparin, Clopidogrel, Apixaban (Eliquis), Dabigatran (Pradaxa), Edoxaban (Savaysa), Rivaroxaban (Xarelto). The use of low dose aspirin (81 mg daily) is acceptable.

25. Known previous intolerance or contraindication to methylprednisolone (for participants to be enrolled in Cohort C)