Clinical trial NCT05079633: A Heterologous Prime-boost Study to Evaluate Immunogenicity and Safety of mRNA-1273 With MVC-COV1901 in Adults
Official title: A Parallel Group, Prospective, Randomized, Double-blind, Two-arm, Single-center Study to Evaluate the Immunogenicity, Safety, and Tolerability of mRNA-1273 in Heterologous Prime-Boost With MVC-COV1901 in Adult Volunteers of 20 to 70 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Covid19 Vaccine
Keywords: Covid19 vaccine
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2021-10-15
Enrollment: 220
Sex: ALL
Minimum age (years): 20
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of the study is to evaluable the safety and to demonstrate the immunogenicity of heterologous prime-boost (mRNA-1273, MVC-COV1901), compared to homologous prime-boost (mRNA-1273), with an interval of 8-12 weeks, This study also assesses the safety and tolerability of the study intervention and explores the immunogenicity by the antigen-specific immunoglobulin, the immunogenicity against the VoCs, the antigen specific cellular immune response, as well as the potential efficacy of study intervention in preventing COVID-19.

Detailed description: This is a parallel group, prospective, randomized, double-blind, two-arm, single-center study to be conducted in approximately 220 healthy participants aged 20 to 70 years who are generally healthy or with stable pre-existing health condition.

The participants should previously have their first dose of mRNA-1273. The participants, investigators, and the site personnel will be blinded to the study intervention assignment until all the participants complete their Day 29. Preparation and administration of study intervention will be performed by authorized unblinded site personnel who do not participate in the evaluation of the participants.

Eligible participants will be randomized to receive either mRNA-1273 or MVC-COV1901 vaccine at a 1:1 ratio. Randomization of participants will be stratified by the interval apart from their first dose of mRNA-1273 (\< 10 weeks or ≥ 10 weeks).

The study consists of 6 on-site visits:

Day -28 to Day 1, Visit 1 (Screening) Day 1, Visit 2 (study intervention) Day 15 ± 3 days, Visit 3 Day 29 ± 3 days, Visit 4 Day 91 ± 14 days, Visit 5 Day 181 ± 14 days, Visit 6 Unscheduled visit(s) may be arranged when deemed necessary by the investigator.

Eligibility criteria: Inclusion Criteria:

1. Male or female participant aged ≥20 to \<70 years at randomization.
2. Has received one dose of the mRNA-1273 8 to 12 weeks before randomization.
3. Female participant must:

   1. Be either of non-childbearing potential, i.e. surgically sterilized (defined as having undergone hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy; tubal ligation alone is not considered sufficient) or one year post-menopausal;
   2. Or, if of childbearing potential, be abstinent or agree to use medically effective contraception from 14 days before screening to 30 days following the last administration of study intervention. Acceptable forms include:

   i. Implanted hormonal methods of contraception or placement of an intrauterine device or intrauterine system ii. Established use of hormonal methods (injectable, pill, patch or ring) combined with barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository c. Have a negative pregnancy test
4. Participant is willing and able to comply with all required study visits and follow-up required by this protocol.
5. Participant or the participant's legal representative must understand the procedures of the study and provide written informed consent.

Exclusion Criteria:

1. Pregnant or breast feeding or have plan to become pregnant within 30 days after the administration of study intervention.
2. Currently receiving or received any investigational intervention within 30 days prior to the study intervention.
3. Administered any licensed live-attenuated vaccines within 28 days or other licensed non-live-attenuated vaccines within 7 days prior to the study intervention.
4. Administered any blood product or intravenous immunoglobulin administration within 12 weeks prior to the study intervention.
5. Currently receiving or anticipate to receive concomitant immunosuppressive or immune-modifying therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or \< 2 weeks of daily receipt of prednisone less than 20 mg or equivalent) within 12 weeks prior to the study intervention.
6. Currently receiving or anticipate to receive treatment with tumor necrosis factor (TNF)-α inhibitors, e.g. infliximab, adalimumab, etanercept within 12 weeks prior to the study intervention.
7. Major surgery or any radiation therapy within 12 weeks prior to the study intervention.
8. Has received any investigational or licensed COVID-19 vaccine other than mRNA-1273, or ≥ two doses of mRNA-1273.
9. Immunosuppressive illness or immunodeficient state, including hematologic malignancy, history of solid organ, bone marrow transplantation, or asplenia.
10. A history of malignancy with potential risk for recurrence after curative treatment, or current diagnosis of or treatment for cancer (exceptions are squamous and basal cell carcinomas of the skin and treated uterine cervical carcinoma in situ, at the discretion of the investigator).
11. Bleeding disorder considered a contraindication to IM injection or phlebotomy.
12. Known SARS-CoV-2 infection in the recent 3 months prior to the study intervention.
13. A history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.
14. Participant who, in the investigator's judgement, is not in a stable condition and by participating in the study could adversely affect the safety of the participant, interfere with adherence to study requirements or evaluation of any study endpoint. This may include a participant with ongoing acute diseases, severe infections, autoimmune disease, laboratory abnormality or serious medical conditions in the following systems: cardiovascular, pulmonary, hepatic, neurologic, metabolic, renal, or psychiatric.
15. A history of hypersensitivity to any vaccine or a history of allergic disease or reactions likely to be exacerbated by any component of the mRNA-1273 or MVC-COV1901.
16. Body (oral, rectal, or ear) temperature ≥ 38.0°C or acute illness (not including minor illnesses such as diarrhea or mild upper respiratory tract infection at the discretion of the investigator) within 2 days before the study intervention.

Primary outcomes:
measure: Primary Immunogenicity-GMT
timeFrame: Day 1 to Day 15
measure: Primary Immunogenicity-SCR
timeFrame: Day 1 to Day 15
measure: Primary Immunogenicity-GMR
timeFrame: Day 1 to Day 15
measure: Primary Safety
timeFrame: Day 1 to Day 29
Secondary outcomes:
measure: Secondary Immunogenicity-GMT
timeFrame: Day 29 to Day 181
measure: Secondary Immunogenicity-SCR
timeFrame: Day 29 to Day 181
measure: Secondary Immunogenicity-GMR
timeFrame: Day 29 to Day 181
measure: Secondary Safety
timeFrame: Day 1 to Day 181
Other outcomes:
measure: Exploratory (antigen-specific immunoglobulin)-GMT
timeFrame: Day 29 to Day 181
measure: Exploratory (antigen-specific immunoglobulin)-SCR
timeFrame: Day 29 to Day 181
measure: Exploratory (antigen-specific immunoglobulin)-GMR
timeFrame: Day 29 to Day 181
measure: Exploratory (VoC)
timeFrame: Day 1 to Day 15
measure: Exploratory (Cell Immunity)
timeFrame: Day 1 to Day 15
measure: Exploratory (Clinical Efficacy)
timeFrame: Day 15 to Day 181
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Szu-Min Hsieh, MD.Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: