A Phase I, Multi-center, Dose Escalation, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of the BMI2012 Against COVID-19 Variant in Healthy Adults Between 19 and 55 Years of Age

BMI Korea

Status and phase: Begins enrollment in 1 month; Phase 1

Conditions: Prevention of COVID-19 Variant (Omicron JN.1)

Treatments: Other: Placebo high-dose; Biological: BMI2012 low-dose; Other: Placebo low-dose; Biological: BMI2012 high-dose; Biological: BMI2012 mid-dose; Other: Placebo mid-dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT07791186

BMI2012-SIT-01

Details and patient eligibility

About

This Phase 1, multi-center, randomized, double-blind, placebo-controlled, dose-escalation study evaluates the safety, tolerability, and immunogenicity of BMI2012, a self-amplifying RNA vaccine candidate targeting the SARS-CoV-2 Omicron JN .1 variant, in healthy adults aged 19 to 55 years.

Participants will be enrolled sequentially into three ascending-dose cohorts and randomized within each cohort to receive a single intramuscular injection of BMI2012 or placebo. A sentinel dosing strategy with staggered administration will be used to monitor safety before enrollment of the remaining participants in each dose cohort. A Data Safety Monitoring Board (DSMB) will review safety data to determine whether enrollment may continue and to assess dose levels appropriate for further clinical development.

The primary objective is to assess the safety and tolerability of BMI2012 across the dose levels studied. Secondary objectives include exploratory evaluation of humoral and cell-mediated immune responses to BMI2012 through 52 weeks after vaccination.

Enrollment: 72 estimated patients

Sex: All

Ages: 19 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

[Inclusion Criteria]

• Male and female, aged 19 to 55 years, who voluntarily decides to participate in this study and provides written informed consent

• Meets at least one of the following:

• (1) At least 3 months have elapsed since the last COVID-19 vaccine administration

• (2)At least 3 months have elapsed since a confirmed diagnosis of COVID-19

• Subjects with a body mass index (BMI) between 18kg/m² and 30 kg/m², inclusive at the screening visit

• Male and female subjects of reproductive potential who have been using a highly effective method of contraception from at least 14 days prior to the screening visit and agree to continue using a highly effective method of contraception** up to 12 weeks after IP administration *Male subjects: Sexual abstinence, or the use of a condom, with the partner of reproductive potential using a highly effective method of contraception** *Female subjects: Use of a highly effective method of contraception**

  • Highly effective methods of contraception are as follows:

• Hormonal contraception associated with inhibition of ovulation

• Intrauterine device (IUD)

• Intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Bilateral tubal ligation

• Bilateral tubal resection/salpingectomy

• Vasectomized partner

• Sexual abstinence

• Subjects who agree not to donate or receive blood (including whole blood, plasma, platelets, or platelet-rich plasma) during the study period

• Subjects who have received and understood a detailed explanation of the study and voluntarily decide to participate in the study and provide written informed consent

• Subjects who are able to comply with all visit procedures, including telephone visits, throughout the study period

[Exclusion Criteria]

• Subjects with a positive rapid antigen test result for COVID-19 at screening
• Subjects currently receiving an approved medicinal product for the treatment or prevention of COVID-19
• Subjects who have had close contact with a person infected with COVID-19, or who have been classified as a confirmed or suspected case of COVID-19, within 14 days prior to IP administration
• Healthcare professionals who may have direct involvement in care of patients confirmed with COVID-19
• Subjects with clinically significant abnormal findings on clinical laboratory tests, electrocardiogram (ECG), or chest X-ray performed at the screening visit
• Subjects with a positive result for any of the following at screening: HIV test, hepatitis B test, or hepatitis C test
• Subjects who had an acute febrile illness with a body temperature of 38°C or higher within 72 hours prior to IP administration, or who are suspected of having another related infectious disease, or who had symptoms due to another infectious disease (such as cough, dyspnea, chills, myalgia, headache, sore throat, anosmia, or ageusia) within the same period
• Subjects judged by the investigator to be unable to participate due to any of the following serious medical or psychiatric conditions:
• (1) Respiratory disease: Asthma, chronic obstructive pulmonary disease (COPD), active tuberculosis, latent tuberculosis under treatment, or other respiratory diseases requiring daily medication; or subjects who have received treatment for exacerbation of the above respiratory diseases within 5 years prior to IP administration
• (2) Serious cardiovascular disease: Congestive heart failure, coronary artery disease, myocardial infarction, uncontrolled hypertension, thrombocytopenic or venous thrombosis, capillary leak syndrome, myocarditis, pericarditis, etc.
• (3) Neurological disease: Epilepsy, seizure disorder (within 3 years prior to IP administration), migraine, stroke, encephalopathy, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, etc.
• (4) History of malignancy within 5 years prior to IP administration (excluding basal cell carcinoma and squamous cell carcinoma of the skin)
• (5) Autoimmune disease, including autoimmune hypothyroidism and psoriasis
• (6) Immunodeficiency disease
• (7) Uncontrolled diabetes mellitus despite appropriate treatment ( HbA1c > 7% at screening)
• (8) A history of dependent use of psychotropic drugs or narcotic analgesics within 24 weeks prior to IP administration, or a psychiatric condition or social circumstance that, in the Investigator's judgment, would make it difficult for the subject to comply with study procedures
• (9) any other hepatobiliary, renal, endocrine, urinary, or musculoskeletal disease judged by the Investigator to be clinically significant
• Subjects with a history of splenectomy
• Subjects with a history of prior infection with SARS-CoV-1 or MERS-CoV
• Subjects with a history of allergy or hypersensitivity to any component of the IP
• Subjects with a history of a SAE, allergy, or hypersensitivity related to vaccination
• Subjects with a history of generalized urticaria within 5 years prior to IP administration
• Subjects with a history of a platelet-related disorder or bleeding disorder, or a history of significant bleeding or bruising following intramuscular injection or venipuncture, or subjects receiving anticoagulant therapy (however, subjects taking low-dose aspirin [≤100 mg/day] may be enrolled at the Investigator's judgment)
• Subjects with a history of hereditary or idiopathic angioedema
• Subjects with a history of organ or bone marrow transplantation
• Subjects with suspected or a history of drug abuse or alcohol abuse within 6 months prior to IP administration
• Subjects who have used immunosuppressants or chronic steroids within 6 months prior to IP administration (however, the use of topical, intranasal, or inhaled steroids is permitted)
• (1) Immunosuppressants: Azathioprine, Cyclosporine, Interferon, G-CSF, Tacrolimus, Everolimus, Sirolimus, Cyclophosphamide, 6-Mercaptopurine, Methotrexate, Rapamycin, Leflunomide, etc.
• (2) Chronic steroid use: Use of a dose exceeding 10mg/day (prednisolone equivalent) for more than 14 consecutive days
• Subjects who have received another investigational product or been treated with another investigational medical device within 6 months prior to the screening visit
• Subjects who are currently participating, or planning to participate, in another clinical study (including the follow-up period of an interventional study)
• Subjects who have received or plan to receive a vaccine within 28 days before or after IP administration (however, as an exception, influenza vaccination is permitted for subjects in the non-Sentinel group if administered at least 2 weeks prior to IP administration)
• Subjects who have received immunoglobulin or a blood product transfusion within 12 weeks prior to IP administration
• Subjects with a scheduled surgery during the study period
• Subjects with a positive pregnancy test result
• Pregnant or breastfeeding women
• Subjects judged by the Investigator to be otherwise unsuitable for participation in this study for any other reason

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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72 participants in 6 patient groups, including a placebo group

Low-dose treatment

Experimental group

Treatment:

Biological: BMI2012 low-dose

Low-dose placebo control

Placebo Comparator group

Treatment:

Other: Placebo low-dose

Mid-dose treatment

Experimental group

Treatment:

Biological: BMI2012 mid-dose

Mid-dose placebo control

Placebo Comparator group

Treatment:

Other: Placebo mid-dose

High-dose treatment

Experimental group

Treatment:

Biological: BMI2012 high-dose

High-dose placebo control

Placebo Comparator group

Treatment:

Other: Placebo high-dose