A clinical study Trial to Evaluate the Safety, Immunogenicity, and Efficacy of INO-4800 in Adults at High Risk of COVID- 19 Disease.

Phase 3

Not yet recruiting

• Conditions: Adults at High Risk ofSARS-CoV-2 Exposure

• Registration Number: CTRI/2022/03/041181
• Lead Sponsor: Inovio Pharmaceuticals Inc

Brief Summary

It is a Phase 2/3 Randomized, Blinded, Placebo-Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of INO-4800, a Prophylactic Vaccine against COVID-19 Disease, Administered Intradermally Followed by Electroporation in Adults at High Risk of SARS-CoV-2 Exposure.

Given the continued number of cases globally, SARS-CoV-2 infections remain a serious unmet medical concern. Appropriate measures to prevent SARS-CoV-2 infections, including its variants, are not yet widely available.

This study is conducted to Evaluate the efficacy of INO-4800 in the prevention of COVID-19 disease in subjects who are SARS-CoV-2 negative at baseline along with to evaluate the safety and tolerability of INO-4800.

Inovio Pharmaceuticals has developed INO-4800 as a DNA vaccine that contains 10 mg/mL of the DNA plasmid pGX9501 in 1X SSC buffer (150 mM sodium chloride and 15 mM sodium citrate). pGX9501 is a DNA plasmid expressing a synthetic consensus (SynCon®) sequence of the SARS-CoV-2 Wuhan-Hu-1 full-length Spike glycoprotein. The ID route of delivery has been selected for INO-4800 based on recent findings from multiple DNA vaccine development programs where ID delivery has driven equivalent if not superior humoral and cellular responses to IM delivery while improving tolerability (clinicaltrials.gov NCT02464670, clinicaltrials.gov NCT02431767). Following ID injection, the Inovio Pharmaceuticals EP device referred to as the CELLECTRA® 2000 for ID administration (3P-ID) device is used to facilitate DNA entry into the cells.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-04
• Last Update Posted: 2022-03-16

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 6714

Inclusion Criteria

• 1.Able to provide informed consent and have signed Informed Consent Form (ICF) prior to screening procedures; 2.Men and non-pregnant women 18 years of age or older; 3.Per investigator judgment, healthy or stable with pre-existing medical conditions that do not require significant change in medication or have led to a hospitalization in the 3 months prior to enrollment or who, in the judgment of the investigator, are unlikely to require a significant change in therapy or hospitalization for worsening disease through Day 56; 4.Able and willing to comply with all study procedures; 5.Working or residing in an environment with high risk of exposure to SARS-CoV-2 for whom exposure may be relatively prolonged or for whom personal protective equipment (PPE) may be inconsistently used, especially in confined settings.
• Examples include: 1.
• Retail/service workers/educators (restaurant waitresses/waiters and bar workers, street vendors, store cashiers, hairdressers and barbers, veterinary staff, daycare workers, airport screening staff, school teachers and college professors teaching in-person classes, college students attending in-person classes, office workers and volunteers who have multiple brief exposures to people regularly) 2.
• Factory workers (when working in confined settings with large numbers of employees, meat-packing facilities) 3.
• Drivers providing bus, taxi or shared ride services (e.g., Uber, Lyft) and delivery services 4.
• User of public transportation (e.g., bus, train, subway) or public facilities (e.g. gyms) at least 3 times weekly 5.
• Nursing home staff or correctional facility staff 6.
• Retirement community residents or adult day program attendees who are regularly eating, socializing and/or exercising in common areas 7.
• Person 51 years or older living in a multigenerational (at least 3 generations) household 8.
• First responders (emergency medical technicians, police who are regularly assigned on patrol) Note: Firefighters typically use face shields and other protective gear but may be considered if they regularly assist with medical emergencies in the field 9.
• Health care workers with prolonged patient interaction (includes nurses and nursing assistants, medical assistants and technicians, respiratory therapists, physical therapists, social workers, dentists and dental hygienists) 10.
• Others, if in the opinion of the PI, the risk of COVID-19 exposure is comparable to the examples above.
• 6.Must meet one of the following criteria with respect to reproductive capacity: 1.
• Women who are post-menopausal as defined by reported spontaneous amenorrhea for ≥ 12 month; 2.
• In the case of vasectomy, subjects should wait six (6) months post-vasectomy prior to enrolling; 3.
• Use of medically effective contraception with a failure rate of < 1% per year when used consistently and correctly from screening until last dose.
• Acceptable methods include: i.
• hormonal contraception including implants, injections or oral; ii.
• two barrier methods, e.g., condom and cervical cap (with spermicide) or diaphragm (with spermicide); iii.
• intrauterine device or intrauterine system; iv.
• Abstinence when this is the subject’s preferred and usual lifestyle.
• Note: Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria

• 1.Acute febrile illness with temperature ≥ 100.4°F (38.0°C) or acute onset of upper or lower respiratory tract symptoms (e.g., cough, shortness of breath, sore throat) on Day 0 prior to dosing; 2.Positive serologic test for SARS-CoV-2 at Screening (this criterion only applies after approximately 402 subjects positive for SARS-CoV-2 serologic test are randomized, after which this criterion will apply to all remaining subjects); 3.Pregnant or breastfeeding, or intending to become pregnant or intending to father children starting from the Screening visit until the last dose; 4.Positive urine pregnancy test during screening or immediately prior to dosing; 5.Known history of uncontrolled HIV based on a CD4 count less than 200 cells/mm3 or a detectable viral load within 3 months prior to screening; 6.Is currently participating or has participated in a study with an investigational product within 30 days prior to Day 0 (documented receipt of placebo in a previous trial would be permissible for trial eligibility); 7.Previous or planned receipt of an investigational (including Emergency Use Authorization (EUA) or local equivalent authorization) or licensed vaccine for prevention or treatment of COVID-19, MERS or SARS (documented receipt of placebo in previous trial would be permissible for trial eligibility); 8.Immunosuppression as a result of underlying illness or treatment including: a)Primary immunodeficiencies (conditions including hypothyroidism, Hashimoto’s thyroiditis and vitiligo are allowed); b)Long term use (≥7 days) of oral or parenteral glucosteroids at a dose of ≥20 mg/day of prednisone equivalent (use of inhaled, topical, nasal, otic, and ophthalmic corticosteroids are allowed) in the past 6 months; c)Current or anticipated use of disease modifying doses of systemic anti-rheumatic drugs (e.g., azathioprine, cyclophosphamide, cyclosporine, methotrexate) and biologic disease modifying drugs such as TNF- α inhibitors (e.g., infliximab, adalimumab or etanercept) or others; d)History of solid organ or bone marrow transplantation; e)History of or current receipt of any other clinically significant immunosuppressive drugs.
• f)Diagnosis of an autoimmune disease that may jeopardize the safety of the subject or require therapy that would interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results.
• 9.Lack of acceptable sites for ID injection and EP considering the skin above the deltoid and anterolateral quadriceps muscles.
• The following are unacceptable sites: a)Tattoos, keloids or hypertrophic scars located within 2 cm of intended administration site; b)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); c)Any metal implants or implantable medical device within the electroporation site; 10.Blood donation or transfusion within 1 month prior to Day 0; 11.People who work remotely or in a socially distanced setting with minimal risk of exposure to SARS-CoV-2; 12.Prisoners or subjects who are compulsorily detained (involuntary incarceration); 13.Reported alcohol or substance abuse/dependence or illicit drug use (excluding marijuana use) within the prior 2 years; 14.Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of virologically-confirmed COVID-19	Day0,week4,week6,week18,week30, week42,week56
of Study (EOS)) in subjects who are SARS-CoV-2	Day0,week4,week6,week18,week30, week42,week56
disease starting 14 days after completion of the	Day0,week4,week6,week18,week30, week42,week56
2-dose regimen until 12 months post-dose 2 (End	Day0,week4,week6,week18,week30, week42,week56
seronegative at baseline.	Day0,week4,week6,week18,week30, week42,week56

Secondary Outcome Measures

Name	Time	Method
. Incidence of severe COVID-19 disease in SARSCoV-2 seronegative subjects starting 14 days	after completion of the 2-dose regimen until EOS
Neutralizing antibody response measured by a	pseudovirus-based neutralization assay
Incidence of virologically-confirmed COVID-19	disease starting 14 days after completion of the
ncidence of adverse events of special interest	(AESIs)
1a. Incidence of solicited and unsolicited injection	site reactions
2.b. Incidence of solicited and unsolicited systemic	adverse events (AEs) by system organ class
1c. Incidence of serious adverse events (SAEs)
Incidence of deaths due to COVID-19 in SARSCoV-2 seronegative subjects starting 14 days	after completion of the 2-dose regimen until EOS
Incidence of all-cause mortality	Day0,week4,week6,week18,week30, week42,week56
Incidence of non-severe COVID-19 disease in	SARS-CoV-2 seronegative subjects starting 14
Antigen-specific cellular immune response	measured by IFN-gamma ELISpot

Trial Locations

Locations (3)

Lifepoint Multispecialty Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Maharaja Agrasen Superspecialty Hospital; 🇮🇳 Jaipur, RAJASTHAN, India

Orchid Speciality Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Lifepoint Multispecialty Hospital

🇮🇳Pune, MAHARASHTRA, India

Dr Sonali Nirhali Chandrakant

Principal investigator

7506213126

sonalinirhali26@gmail.com