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

Phase 1

Completed

Conditions: COVID-19

Interventions: Biological: GRAd-COV2

Registration Number: NCT04528641

Lead Sponsor: ReiThera Srl

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 98

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm 3 - High dose	GRAd-COV2	Arm-3 Healthy adult volunteers aged 18-55y will receive IM single dose of 2e11vp. N=15
Arm 1 - Low dose	GRAd-COV2	Arm-1 Healthy adult volunteers aged 18-55y will receive IM single dose of 5e10vp. N=15
Arm 4 - Low dose	GRAd-COV2	Arm-4 Healthy elderly volunteers aged 65-85y will receive IM single dose of 5e10vp. N=16
Arm 5 - Intermediate dose	GRAd-COV2	Arm-5 Healthy elderly volunteers aged 65-85y will receive IM single dose of 1e11vp. N=15
Arm 2 - Intermediate dose	GRAd-COV2	Arm-2 Healthy adult volunteers aged 18-55y will receive IM single dose of 1e11vp. N=15
Arm 6 - High dose	GRAd-COV2	Arm-6 Healthy elderly volunteers aged 65-85y will receive IM single dose of 2e11vp. N=15

Primary Outcome Measures

Name	Time	Method
Occurrence of Solicited Local AE Signs and Symptoms 7 Days Following the Vaccination	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.
Occurrence of Solicited Systemic AE Signs and Symptoms 7 Days Following the Vaccination	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.
Occurrence of Unsolicited AE 28 Days Following the Vaccination	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.
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 Platelets From Baseline	Weeks 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 Direct Bilirubin Form Baseline	week 1,2,4,8,12, and 24
Occurrence of Serious AE 24 Weeks Following the Vaccination	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)
Change in Leucocytes From Baseline	baseline, Weeks 1,2,4,8,12, and 24
Change in Neutrophils From Baseline	Weeks 1,2,4,8,12, and 24	Change from baseline was calculated as the value at each week minus the value at the baseline.
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 Sodium From Baseline	week 1,2,4,8,12, and 24
Change in Monocytes From Baseline	Weeks 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 Hemoglobin From Baseline	Weeks 1,2,4,8,12, and 24
Change in Aspartate Aminotransferase From Baseline	week 1,2,4,8,12, and 24
Change in Bilirubin From Baseline	week 1,2,4,8,12, and 24
Change in Urea Nitrogen From Baseline	week 1,2,4,8,12, and 24
Change in Albumin Form Baseline	week 1,2,4,8,12, and 24

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Positive, Negative or Indeterminate Seroconversion for Anti-s Antibody	week 1, 2, 4, 8, 12, and 24	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.
Number of Participants With Positive, Negative Anti-n Antibody	week 1, 2, 4, 8, 12 and 24	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
Number of Participants With Positive, Negative for Micro Neutralization Test	week 4 and week 24	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
Immunogenicity - T-cell Response	baseline, week 2, week 4, week 8, week 12, week 24	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.