Phase I Study to Assess the Safety and Immunology of a COVID-19 Vaccine With GRAd-COV2 Vaccine

Study Overview
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Brief Summary
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RT-CoV-2 is a Phase I, open-label, dose escalation multicenter clinical trial to assess safety and immunogenicity of the candidate Coronavirus disease (COVID-19) vaccine GRAd-COV2 in Italian healthy volunteers aged 18-55 years and 65-85 years inclusive. GRAd-COV2 is based on a novel replication defective Gorilla Adenovirus and encodes for SARS-COV-2 Spike protein.

Detailed Description
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RT-CoV-2 is a Phase I, open-label, dose escalation multicenter clinical trial to assess safety and immunogenicity of the candidate Coronavirus disease (COVID-19) vaccine GRAd-COV2 in Italian healthy volunteers aged 18-55 years and 65-85 years inclusive. GRAd-COV2 is based on a novel replication defective Gorilla Adenovirus and encodes for SARS-COV-2 full length prefusion stabilized Spike protein. GRAd-COV2 is developed and manufactured by ReiThera Srl. This study will evaluate a singular intramuscular administration of GRAd-COV2 at 3 dose levels: 5e10, 1e11, 2e11viral particles (vp). There will be 6 study arms for a total of 90 healthy volunteers, divided into 2 cohorts of age, 18-55y and 65-85y, respectively. Participants will be followed up for 24 weeks after vaccination. Follow up includes safety and immunogenicity assessment. Follow up visits will occur at day2, then 1, 2, 4, 8, 12, 24 weeks after vaccination. The primary objective is to evaluate the safety and reactogenicity of a single dose vaccination schedule of GRAd-COV2 across 3 dosages in healthy younger and older adults. The secondary objective is to evaluate humoral and cellular immunogenicity.

Official Title
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A Phase 1, Dosage-Escalation Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine GRAd-COV2 in Healthy Adults and Elderly Subjects

Conditions
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COVID-19

Intervention / Treatment
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* Biological: GRAd-COV2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A subject must meet all of the following criteria to be eligible to participate in this study: Provides written informed consent prior to initiation of any study procedures. Be able to understand and agrees to comply with planned study procedures and be available for all study visits. Agrees to the collection of venous blood per protocol. Confirms to have not donated blood three months before the study Agrees to refrain from blood during the study and until the three months after the end of the study. Body Mass Index 18-29 kg/m2, inclusive, at screening. Premenopausal women must agree to use one acceptable primary form of contraception. Premenopausal women must have a negative urine pregnancy test the day of vaccination and are routinely using - and willing to use up to six months from vaccine administration - an effective method of birth control resulting in a low failure rate (i.e., hormonal contraception, condoms in combination with a spermicidal cream, male partner sterilization-vasectomy or total sexual abstinence). Oral temperature ≤37.0 degrees Celsius the day of the administration of the vaccine Pulse no greater than 100 beats per minute. Systolic blood pressure (BP) is 85 to 139 mmHg, inclusive the day of vaccination. Should not show laboratory values outside the normal range which may have clinical significance even in absence of specific signs or symptoms. Exclusion Criteria: A subject who meets any of the following criteria will be excluded from participation in this study: Positive serology for anti-HIV-Ab Positive HbBsAg Positive anti-HCV-Ab Positive for SARS-CoV-2 (either anti-S-Ab or anti-N-Ab) Acute illness, as determined by the site PI or appropriate sub-investigator, the day of vaccination. Breastfeeding women Autoimmune and hyper-inflammatory condition History of atopy (or any IgE associated condition) who had required treatment over the last 6 months; History of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines; Assumption of any immunomodulatory medication over the last 4 months (including, but not limited to, systemic corticosteroids, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs). The use of low dose topical, ophthalmic, inhaled, and intranasal steroid preparations will be permitted. Presence of self-reported or medically documented significant medical condition Presence of self-reported or medically documented significant psychiatric condition Significant cardiovascular disease needing therapy or history of myocarditis or pericarditis or heart surgery. Patients in treatment with Sartans or ACE-Inhibitors and good response to therapy may be included. Neurological or neurodevelopmental conditions (e.g., history of migraines in the past 5 years, epilepsy, stroke, seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis or transverse myelitis). Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, which are allowed. Primary or secondary immunodeficiency of any cause. Participated in another investigational study involving vaccination of biologic compounds in the last 12 months. Currently enrolled in or plans to participate in another clinical trial with an investigational agent that will be received during the study-reporting period. Administration of immunoglobulins and/or any blood or blood products within the 4 months before the first vaccine administration or at any time during the study. Has any significant disorder of coagulation. Has any chronic liver disease, including fatty liver. Has a history of alcohol abuse or other recreational drug use within 6 months before the first vaccine administration. Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site (deltoid region). Received or plans to receive additional vaccination within 4 weeks before or after each vaccination. Has been reported as a case (confirmed or probable) of COVID-19 from the regional health system Has any clinical conditions that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation, this includes any acute, subacute, intermittent or chronic medical disease or condition that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Phase I, open-label, dose escalation, clinical trial to assess the safety and immunogenicity of the candidate GRAd-COV2 vaccine in 90 healthy volunteers aged 18-55 years and elderly volunteers aged 65-85 years. The vaccine will be administered intramuscularly once in time.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 - Low dose<br>Arm-1 Healthy adult volunteers aged 18-55y will receive IM single dose of 5e10vp. N=15 | Biological: GRAd-COV2<br>* Single intramuscular administration.<br>|
| Experimental: Arm 2 - Intermediate dose<br>Arm-2 Healthy adult volunteers aged 18-55y will receive IM single dose of 1e11vp. N=15 | Biological: GRAd-COV2<br>* Single intramuscular administration.<br>|
| Experimental: Arm 3 - High dose<br>Arm-3 Healthy adult volunteers aged 18-55y will receive IM single dose of 2e11vp. N=15 | Biological: GRAd-COV2<br>* Single intramuscular administration.<br>|
| Experimental: Arm 4 - Low dose<br>Arm-4 Healthy elderly volunteers aged 65-85y will receive IM single dose of 5e10vp. N=16 | Biological: GRAd-COV2<br>* Single intramuscular administration.<br>|
| Experimental: Arm 5 - Intermediate dose<br>Arm-5 Healthy elderly volunteers aged 65-85y will receive IM single dose of 1e11vp. N=15 | Biological: GRAd-COV2<br>* Single intramuscular administration.<br>|
| Experimental: Arm 6 - High dose<br>Arm-6 Healthy elderly volunteers aged 65-85y will receive IM single dose of 2e11vp. N=15 | Biological: GRAd-COV2<br>* Single intramuscular administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Solicited Local AE Signs and Symptoms 7 Days Following the Vaccination | Participants were monitored for 7 days post-vaccination and the occurrence of solicited local AE signs and symptoms were collected. | 7 days following the vaccination | 
| Occurrence of Solicited Systemic AE Signs and Symptoms 7 Days Following the Vaccination | Participants were monitored for 7 days post-vaccination and the occurrence of solicited systemic AE signs and symptoms were collected. | 7 days following the vaccination | 
| Occurrence of Unsolicited AE 28 Days Following the Vaccination | Occurrence of unsolicited AEs: unsolicited AEs were collected using the patient Diary and reported as Any AE occurring 28 days following the vaccination. | 28 days following the vaccination | 
| Occurrence of Serious AE 24 Weeks Following the Vaccination | Occurrence of any treatment - emergent serious AE and treatment - emergent SAE related to study drug was monitored during the study period (24 weeks following vaccination) | 24 weeks following the vaccination | 
| Change in Leucocytes From Baseline |  | baseline, Weeks 1,2,4,8,12, and 24 | 
| Change in Basophils From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Eosinophils From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Neutrophils From Baseline | Change from baseline was calculated as the value at each week minus the value at the baseline. | Weeks 1,2,4,8,12, and 24 | 
| Change in Monocytes From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Lymphocytes From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Erythrocytes From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Hematocrit From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Platelets From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Hemoglobin From Baseline |  | Weeks 1,2,4,8,12, and 24 | 
| Change in Sodium From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Potassium From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Alkaline Phosphatase From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Alanine Aminotransferase From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Aspartate Aminotransferase From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Direct Bilirubin Form Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Bilirubin From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Albumin Form Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Creatinine Form Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Lactate Dehydrogenase From Baseline |  | week 1,2,4,8,12, and 24 | 
| Change in Urea Nitrogen From Baseline |  | week 1,2,4,8,12, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive, Negative or Indeterminate Seroconversion for Anti-s Antibody | To assess the cellular and humoral immune response to SARS-CoV2 elicited by the vaccine Immunogenicity Result: Seroconversion for Anti-S Antibody Interpretation: n. of subjects positive, negative or indeterminate at week 1, 2, 4, 8, 12, and 24 after vaccination. | week 1, 2, 4, 8, 12, and 24 | 
| Number of Participants With Positive, Negative Anti-n Antibody | To assess the cellular and humoral immune response to SARS-CoV2 elicited by the vaccine cellular and humoral immune parameters evaluated: anti-N Antibody Interpretation: n. of subjects positive, negative at week 1, 2, 4, 8, 12 and 24 compared to baseline | week 1, 2, 4, 8, 12 and 24 | 
| Number of Participants With Positive, Negative for Micro Neutralization Test | To assess the cellular and humoral immune response to SARS-CoV2 elicited by the vaccine cellular and humoral immune parameters evaluated: Micro Neutralization test Interpretation: n. of positive and negative subjects at week 4 and week 24 by evaluating geometric mean titer change from baseline | week 4 and week 24 | 
| Immunogenicity - T-cell Response | To assess the cellular and humoral immune response to SARS-CoV2 elicited by the vaccine cellular and humoral immune parameters evaluated. T-cells were evaluated on frozen and fresh (week2) samples Within-cohort comparisons to assess the difference in immune response according to different doses in the same population Across-the-cohort comparison to assess whether elderlies and adults have a different pattern of immune response after vaccination at different endpoints Unit: spot-forming cells [SFC]/1 × 10^6 peripheral blood mononuclear cell [PBMC] Interpretation: values higher than at baseline are indicative of a persistent spike-specific memory T-cell establishment. | baseline, week 2, week 4, week 8, week 12, week 24 |