Phase I single-center safety and immunogenicity study of aAVC-CoV-2, a novel vaccine modality for the prevention of COVID-19 infection in adults with antibody-producing failure.

JRCT ID: jRCT2063240097

Registered date:24/12/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients with mature B-cell tumors with anntibody-producing failure
• Date of first enrollment: 25/12/2024
• Target sample size: 10
• Study type: Interventional

Intervention(s)

In Cohort 1 (low-dose), two doses of the investigational product (aAVC-CoV-2) 1-dose 5*107 cells/body are given 24 weeks apart.
In Cohort 2 (high-dose), two doses of the investigational product (aAVC-CoV-2) 1-dose 1*108 cells/body are given 24 weeks apart.

Outcome(s)

• Primary Outcome: Safety
• Secondary Outcome: Immunological effects (antigen-specific T-cell immune responses, antibody titers)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1)Patients who are free to obtain written informed consent to participate in the study.
2)Patients 18 years or older at the time of informed consent.
3)Patients who meet diagnostic criteria for a mature B-cell tumor of the index or relapse based on the definition of the 5th edition of the Hematopoietic Tumor WHO Classification (2022) and who are in complete response (CR) status based on the definition of Lugano Classification (2014) revised Response Evaluation Criteria according to the administration of antineoplastic agents.
4)It has been informed that it is a mature B-cell tumor.
5)ECOG Performance status is 1 or less.
6)12 Survival beyond a week is expected.

Exclude criteria

1)Individuals with ongoing Grade 2 and uncontrolled non-hematologic toxicities in CTCAE v5.0-JCOG with the impact of pretreatment of mature B-cell neoplasms.
2)Individuals undergoing allogeneic hematopoietic stem-cell transplantation with ongoing clinically significant and treatment-requiring graft-versus-host disease (GVHD).
3)Patients undergoing the following procedures or procedures before administration of the investigational product within the following time period.
General immunosuppressive drugs including steroids: 14 days
Other investigational products, investigational products, and medical devices for clinical trials: 28 days
Autologous and allogeneic hematopoietic stem cell transplantation: 56 days
Antineoplastic agents: 28 days
SARS-CoV-2 vaccination: 180 d
4)Patients who meet the following criteria for laboratory tests etc. within 30 days before enrollment.
AST and ALT levels more than 3 times ULN of the study site
Direct bilirubin level more than twice as high as ULN
Total lymphocyte count in peripheral blood <=5.0*102/microL
eGFR levels below 30 mL/min
Percutaneous arterial oxygen-saturation<94% with room air
5)Individuals with a history of COVID-19 in the 180 days prior to enrollment.
6)Subjects who have a history of allergic symptoms such as generalized exanthema or severe hypersensitivity (anaphylaxis, etc.) following vaccination with COVID-19 prophylaxis.
7)Patients with a history of previous seizures (excluding febrile seizures).
8)Patients who plan to use drugs and therapies listed on prohibited concomitant medications.
9)Patients who were transfused or received a gamma globulin preparation within 30 days prior to the day of study vaccination or patients who received high-dose gamma globulin preparation therapy (200 mg/kg or higher) within 180 days.
10)Individuals scheduled for SARS-CoV-2 vaccination during the study.
11)Patients who are scheduled to participate in other clinical trials or clinical trials (excluding observational studies) by the end of the follow-up period of this study.
12)Patients with double cancer (including a history of cancer within 5 years of disease-free interval).
However, patients with intraepithelial or intramucosal cancer who are considered to be cured after local therapy are not included.
13)Subjects with a history of angina pectoris or myocardial infarction in the 12 weeks prior to administration of the investigational product, congestive heart failure with III or greater on NYHA cardiac function, or serious ECG abnormalities.
14)Patients with uncontrolled hypertension.
15)Patients with interstitial pneumonia, pulmonary fibrosis.
They also have chronic obstructive pulmonary disease of stage III or higher in Guideline-2022 [6th edition] for diagnosing and treating COPD (chronic obstructive pulmonary disease).
16)Individuals with disseminated intravascular coagulation (DIC).
17)Patients with active and uncontrolled infections.
18)Patients with active B, C viral hepatitis or other active liver disease.
19)Patients with confirmed HIV infection or patients with acquired immunodeficiency syndrome.
20)Patients with congenital immunodeficiency syndrome.
21)Patients who are pregnant or possibly pregnant or breastfeeding.
Women who are breastfeeding will not be enrolled in the study due to breastfeeding interruption.
22)Patients wishing to become pregnant during the study period.
Patients who cannot use effective contraception.
23)Patients with uncontrolled diabetes mellitus who fall under any of the following:
Insulin-dose failure to maintain fasting glucose <-200mg/dL.
Treatment with insulin results in two or more episodes of hypoglycemia per day.
With ketoacidosis.
With hyperosmolar nonketotic coma.
24)Individuals with a history of hypersensitivity to product components or to components used in product manufacturing process (animal-derived components).
25) Patients with with a history of other serious allergies.
26)Patients who are considered unsuitable for participation in the study by the investigator as a result of screening tests.
27)Other patients who are judged as inappropriate by the principal investigator or the subinvestigator.

Related Information

• Primary Sponsor: Kadowaki Norimitsu
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development