Clinical trial NCT04528641: Phase I Study to Assess the Safety and Immunology of a COVID-19 Vaccine With GRAd-COV2 Vaccine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Lead sponsor: ReiThera Srl
Sponsor class: INDUSTRY
Collaborators: name: Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS
First posted: 2020-08-27
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

A subject must meet all of the following criteria to be eligible to participate in this study:

1. Provides written informed consent prior to initiation of any study procedures.
2. Be able to understand and agrees to comply with planned study procedures and be available for all study visits.
3. Agrees to the collection of venous blood per protocol.
4. Confirms to have not donated blood three months before the study
5. Agrees to refrain from blood during the study and until the three months after the end of the study.
6. Body Mass Index 18-29 kg/m2, inclusive, at screening.
7. Premenopausal women must agree to use one acceptable primary form of contraception.
8. 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).
9. Oral temperature ≤37.0 degrees Celsius the day of the administration of the vaccine
10. Pulse no greater than 100 beats per minute.
11. Systolic blood pressure (BP) is 85 to 139 mmHg, inclusive the day of vaccination.
12. 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:

1. Positive serology for anti-HIV-Ab
2. Positive HbBsAg
3. Positive anti-HCV-Ab
4. Positive for SARS-CoV-2 (either anti-S-Ab or anti-N-Ab)
5. Acute illness, as determined by the site PI or appropriate sub-investigator, the day of vaccination.
6. Breastfeeding women
7. Autoimmune and hyper-inflammatory condition
8. History of atopy (or any IgE associated condition) who had required treatment over the last 6 months;
9. History of hypersensitivity or severe allergic reaction (e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction) to any previous licensed or unlicensed vaccines;
10. 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.
11. Presence of self-reported or medically documented significant medical condition
12. Presence of self-reported or medically documented significant psychiatric condition
13. 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.
14. 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).
15. 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.
16. Primary or secondary immunodeficiency of any cause.
17. Participated in another investigational study involving vaccination of biologic compounds in the last 12 months.
18. Currently enrolled in or plans to participate in another clinical trial with an investigational agent that will be received during the study-reporting period.
19. 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.
20. Has any significant disorder of coagulation.
21. Has any chronic liver disease, including fatty liver.
22. Has a history of alcohol abuse or other recreational drug use within 6 months before the first vaccine administration.
23. 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).
24. Received or plans to receive additional vaccination within 4 weeks before or after each vaccination.
25. Has been reported as a case (confirmed or probable) of COVID-19 from the regional health system
26. 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

Primary outcomes:
measure: Occurrence of Solicited Local AE Signs and Symptoms 7 Days Following the Vaccination
timeFrame: 7 days following the vaccination
measure: Occurrence of Solicited Systemic AE Signs and Symptoms 7 Days Following the Vaccination
timeFrame: 7 days following the vaccination
measure: Occurrence of Unsolicited AE 28 Days Following the Vaccination
timeFrame: 28 days following the vaccination
measure: Occurrence of Serious AE 24 Weeks Following the Vaccination
timeFrame: 24 weeks following the vaccination
measure: Change in Leucocytes From Baseline
timeFrame: baseline, Weeks 1,2,4,8,12, and 24
measure: Change in Basophils From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Eosinophils From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Neutrophils From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Monocytes From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Lymphocytes From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Erythrocytes From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Hematocrit From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Platelets From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Hemoglobin From Baseline
timeFrame: Weeks 1,2,4,8,12, and 24
measure: Change in Sodium From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Potassium From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Alkaline Phosphatase From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Alanine Aminotransferase From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Aspartate Aminotransferase From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Direct Bilirubin Form Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Bilirubin From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Albumin Form Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Creatinine Form Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Lactate Dehydrogenase From Baseline
timeFrame: week 1,2,4,8,12, and 24
measure: Change in Urea Nitrogen From Baseline
timeFrame: week 1,2,4,8,12, and 24
Secondary outcomes:
measure: Number of Participants With Positive, Negative or Indeterminate Seroconversion for Anti-s Antibody
timeFrame: week 1, 2, 4, 8, 12, and 24
measure: Number of Participants With Positive, Negative Anti-n Antibody
timeFrame: week 1, 2, 4, 8, 12 and 24
measure: Number of Participants With Positive, Negative for Micro Neutralization Test
timeFrame: week 4 and week 24
measure: Immunogenicity - T-cell Response
timeFrame: baseline, week 2, week 4, week 8, week 12, week 24
Other outcomes:
Locations:
city: Rome
country: Italy
facility: INMI Spallanzani
city: Verona
country: Italy
facility: Centro Ricerche Cliniche
Study officials:
affiliation: Istituto Nazionale per le Malattie Infettive "Lazzaro Spallanzani" IRCCS
name: Simone Lanini
role: PRINCIPAL_INVESTIGATOR
References:
citation: Capone S, Raggioli A, Gentile M, Battella S, Lahm A, Sommella A, Contino AM, Urbanowicz RA, Scala R, Barra F, Leuzzi A, Lilli E, Miselli G, Noto A, Ferraiuolo M, Talotta F, Tsoleridis T, Castilletti C, Matusali G, Colavita F, Lapa D, Meschi S, Capobianchi M, Soriani M, Folgori A, Ball JK, Colloca S, Vitelli A. Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19. Mol Ther. 2021 Aug 4;29(8):2412-2423. doi: 10.1016/j.ymthe.2021.04.022. Epub 2021 Apr 23.