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Trial registered on ANZCTR


Registration number
ACTRN12624000294550
Ethics application status
Approved
Date submitted
9/02/2024
Date registered
21/03/2024
Date last updated
6/11/2024
Date data sharing statement initially provided
21/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Intramuscular versus Subcutaneous COVID-19 needle length RCT
Scientific title
Randomized Controlled Trial of COVID-19 booster vaccine for intramuscular versus subcutaneous administration assessing immunogenicity and reactogenicity. in pharmacies/vaccination sites in Aotearoa, New Zealand.
Secondary ID [1] 311425 0
MRINZ-23-13
Universal Trial Number (UTN)
U1111-1298-2507
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 332714 0
Condition category
Condition code
Infection 329427 329427 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pfizer Comirnaty Omicron XBB.1.5 COVID-19 booster vaccine administered by 12.7mm needle (subcutaneous), lateral upper arm. Single 0.3ml dose administered only once by a pharmacist/registered vaccinator.
Intervention code [1] 327871 0
Prevention
Comparator / control treatment
Pfizer Comirnaty Omicron XBB.1.5 COVID-19 booster vaccine administered by 12.7mm needle (intramuscular), deltoid muscle of the upper arm. Single 0.3ml dose administered only once by a pharmacist/registered vaccinator.
Control group
Active

Outcomes
Primary outcome [1] 337297 0
Assess the immunogenicity of subcutaneous (SC) versus intramuscular (IM) vaccine delivery
Timepoint [1] 337297 0
Day -14 prior vaccination and day 28 post vaccination
Secondary outcome [1] 431383 0
Compare reactogenicity of subcutaneous versus intramuscular delivery
Timepoint [1] 431383 0
week 1 (day 1 - day 7) post vaccination
Secondary outcome [2] 431384 0
Compare the reactogenicity of subcutaneous versus intramuscular vaccine delivery
Timepoint [2] 431384 0
Day 28 (Week 4) post vaccination
Secondary outcome [3] 431385 0
Assess the difference in Neutralising antibodies against SARS-COV-2 XBB.1.5 in serum
Timepoint [3] 431385 0
Day 28 (week 4) post vaccination
Secondary outcome [4] 431386 0
Assess the reactogenicity of subcutaneous versus intramuscular vaccine delivery.
Timepoint [4] 431386 0
Day 1 - Day 7 post vaccination
Secondary outcome [5] 431387 0
Assess for COVID-19 infection.
Timepoint [5] 431387 0
Day 28 (Week 4) post vaccination
Secondary outcome [6] 431388 0
Assessment of safety
Timepoint [6] 431388 0
Day 105 (Week 15) post vaccination
Secondary outcome [7] 432067 0
Compare the reactogenicity of SC versus IM vaccine delivery
Timepoint [7] 432067 0
Day 1 - day 7 post vaccination
Secondary outcome [8] 432068 0
Compare the reactogenicity of SC versus IM vaccine delivery.
Timepoint [8] 432068 0
Day 1 - day 7 (week 1) post vaccination
Secondary outcome [9] 432069 0
Compare the reactogenicity of SC versus IM vaccine delivery
Timepoint [9] 432069 0
Day 1 - day 7 (week 1) post vaccination
Secondary outcome [10] 432070 0
Compare the reactogenicity of SC versus IM vaccine delivery
Timepoint [10] 432070 0
Day 1 - day 7 (week 1) post vaccination
Secondary outcome [11] 432071 0
Compare the reactogenicity of SC versus IM vaccine delivery
Timepoint [11] 432071 0
Day 1 - day 7 (week 1) post vaccination
Secondary outcome [12] 432072 0
Compare the reactogenicity of SC versus IM vaccine delivery
Timepoint [12] 432072 0
Day 28 (Week 4) post vaccination
Secondary outcome [13] 432089 0
Assessment of safety
Timepoint [13] 432089 0
Day 105 (week 15) post vaccination
Secondary outcome [14] 441475 0
Assess difference in Neutralising antibodies against SARS-COV-2 XXB 1.5 in serum.
Timepoint [14] 441475 0
Secondary outcome [15] 441476 0
Assess difference in Neutralising antibodies against SARS-COV-2 XXB 1.5 in serum.
Timepoint [15] 441476 0
Week 4 (Day 28) post vaccination
Secondary outcome [16] 441477 0
Assess difference in Neutralising antibodies against SARS-COV-2 XXB 1.5 in serum.
Timepoint [16] 441477 0
Week 4 (Day 28) post vaccination
Secondary outcome [17] 441478 0
Assess difference in Neutralising antibodies against SARS-COV-2 XXB 1.5 in serum.
Timepoint [17] 441478 0
Week 4 (Day 28) post vaccination
Secondary outcome [18] 441479 0
Assess Neutralising antibodies against XBB1.5 waning in serum.
Timepoint [18] 441479 0
Week 4 (Day 28) post vaccination
Secondary outcome [19] 441480 0
Assess Neutralising antibodies against XBB1.5 waning in serum.
Timepoint [19] 441480 0
Week 4 (Day 28) post vaccination Week 15 (Day 105) post vaccination
Secondary outcome [20] 441481 0
Assess Neutralising antibodies against XBB1.5 waning in serum.
Timepoint [20] 441481 0
Week 4 (Day 28) post vaccination Week 15 (Day 105) post vaccination
Secondary outcome [21] 441482 0
Assess Neutralising antibodies against XBB1.5 waning in serum.
Timepoint [21] 441482 0
Week 15 (day 105) post vaccination Week 4 (day 28) post vaccination
Secondary outcome [22] 441483 0
Assess for COVID-19 infection post vaccination.
Timepoint [22] 441483 0
Week 15 (day 105) post vaccination Week 4 (day 28) post vaccination
Secondary outcome [23] 441484 0
Assess for COVID-19 infection post vaccination.
Timepoint [23] 441484 0
Week 4 (Day 28) post vaccination Week 15 (Day 105) post vaccination
Secondary outcome [24] 441485 0
Assessment of vaccine hesitancy
Timepoint [24] 441485 0
Week 4 (Day 28) post vaccination Week 15 (Day 105) post vaccination
Secondary outcome [25] 441486 0
Assessment of vaccine hesitancy
Timepoint [25] 441486 0
Screening before vaccination Week 4 (Day 28) post vaccination
Secondary outcome [26] 441487 0
Assessment of arm circumference at vaccination visit
Timepoint [26] 441487 0
Screening before vaccination Week 4 (Day 28) post vaccination
Secondary outcome [27] 441488 0
Assessment of arm circumference at vaccination visit
Timepoint [27] 441488 0
Vaccination visit (Day 1)

Eligibility
Key inclusion criteria
1. Adult aged 18 – 75 years.
2. BMI cutoff points will be determined by sex assigned at birth. Female with BMI >30.2 kg/m2 or male with BMI >37.3 kg/m2
3. Have received at least 2 previous COVID-19 vaccinations.
4. Be eligible to receive Pfizer Comirnaty COVID-19 booster vaccine.
5. Participant must be willing and able to provide written informed consent.
6. Access to a mobile phone and/or device with internet connectivity to complete remote diary entries and surveys.
7. Willing and able to comply with the study instructions.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Positive COVID-19 infection within 6 months prior to screening.
2. Received COVID-19 vaccination within 6 months prior to screening.
3. History or anaphylaxis, allergic disease, severe reactions to COVID vaccine, or reaction likely to be exacerbated by any component or study participation.
4. Cognitive impairment that prevents the participant from understanding the study instructions, completing questionnaires, or providing informed consent.
5. Is acutely ill or febrile 72 hours prior to or at vaccination visit. Fever is defined as a body temperature greater than 38.0°C.
6. Individuals receiving treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planes receipt throughout the study. If systemic corticosteroids have been administered short term for treatment of acute illness, participants should not be enrolled into study until corticosteroid therapy has been discontinued for at least 28 days before study vaccine is administered. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
7. Any contraindication to IM, SC injections or blood tests including but not limited to bleeding disorders.
8. Is pregnant.
9. Has received or plans to receive immunoglobulins or any blood products within 3 months before the study vaccination through to the end of the study.
10. Has received or plans to receive any non-study vaccinations within 14 days prior to screening or 28 days after dose of study vaccine.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will undergo central randomisation by computer in a 1:1 ratio to receive the Pfizer Comirnaty COVID-19 booster vaccine with a 12.7 mm needle or 38 mm needle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will take place electronically within the REDCap CDMA, using the inbuilt randomisation module. Investigators will not have access to the randomisation schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
It is uncertain what size difference in mean percentage inhibition of Neutralising antibody against XBB1.5 strain may be clinically important, particularly as the recruitment population has been previously exposed to other strains of the virus. We are also limited in the resources available to recruit participants. We have sufficient resources to recruit a total of 400 participants, and assuming a 15% drop out rate, means that we should have complete data on 340 participants. This sample size has 90% power to detect an effect size difference of 0.35, which falls between a small (effect size 0.2) and medium (effect size 0.5) effect, based on the Cohen discussion of effect sizes. An interim analysis will be performed to define, based on the Root Mean Square Error (RMSE), what an effect size of 0.35 means in terms of the RMSE, and whether, based on subject-matter knowledge, this is likely to be a meaningful difference. The interim analysis will not change recruitment or sample size.
Interim analysis will use data from the first 30 enrolled participants who have had their baseline and day 28 bloods taken. The primary objective of this analysis is to confirm that normality distribution assumptions are met. This will be by visual inspection of relevant plots e.g. QQ-plots of standardized residuals, frequency histograms of standardized residuals, and formal tests of normality of residuals. Dependent on the possible violation of normality assumptions appropriate transformations of the outcomes e.g. a logarithm transformation, will be used and normality assumptions reviewed on the transformed scale. If normality assumptions are still not well-met, the planned primary analysis will be changed to the Mann-Whitney test with the Hodges-Lehmann estimator of location difference. If normality assumptions are reasonably well-met on either the raw or transformed scales then the estimated Root Mean Square Error (RMSE) will be discussed with the subject matter experts to aid in deciding about how the size difference the study is able to detect, see the sample size discussion below.

The primary outcome is the percentage inhibition of Neutralising antibodies against XBB1.5 strain. If normality assumptions are not well-met in the interim analysis, then data transformations will be explored, and failing identifying a suitable data transformation, planning for a rank-based test e.g. Mann-Whitney test with the Hodges-Lehmann estimator of location difference.

Secondary objectives will be by ANCOVA, estimation of relative risk and Poisson regression

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/06/2024
Actual
1/07/2024
Date of last participant enrolment
Anticipated
30/03/2025
Actual
Date of last data collection
Anticipated
13/07/2025
Actual
Sample size
Target
400
Accrual to date
65
Final
Recruitment outside Australia
Country [1] 26135 0
New Zealand
State/province [1] 26135 0

Funding & Sponsors
Funding source category [1] 315698 0
Other Collaborative groups
Name [1] 315698 0
Te Niwha Infectious Diseases Research Platform
Country [1] 315698 0
New Zealand
Primary sponsor type
Other
Name
Medical Research Institute of New Zealand (MRINZ)
Address
Country
New Zealand
Secondary sponsor category [1] 317868 0
None
Name [1] 317868 0
None
Address [1] 317868 0
Country [1] 317868 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314566 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 314566 0
Ethics committee country [1] 314566 0
New Zealand
Date submitted for ethics approval [1] 314566 0
09/02/2024
Approval date [1] 314566 0
12/03/2024
Ethics approval number [1] 314566 0
2024 FULL 18986

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132034 0
Dr Gabby Shortt
Address 132034 0
7 CSB building wellington hospital, Riddiford street, Newtown, 6021, Wellington
Country 132034 0
New Zealand
Phone 132034 0
+64 805 0261
Fax 132034 0
Email 132034 0
gabby.shortt@mrinz.ac.nz
Contact person for public queries
Name 132035 0
Gabby Shortt
Address 132035 0
7 CSB building wellington hospital, Riddiford street, Newtown, 6021, Wellington
Country 132035 0
New Zealand
Phone 132035 0
+64 805 0261
Fax 132035 0
Email 132035 0
gabby.shortt@mrinz.ac.nz
Contact person for scientific queries
Name 132036 0
Gabby Shortt
Address 132036 0
7 CSB building wellington hospital, Riddiford street, Newtown, 6021, Wellington
Country 132036 0
New Zealand
Phone 132036 0
+64 805 0261
Fax 132036 0
Email 132036 0
gabby.shortt@mrinz.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identifed data underlying published results only.
When will data be available (start and end dates)?
Data will be available immediately following publication; no end date determined
Available to whom?
Researchers who provide a methodologically sound proposal, assessed on a case-by-case basis at the discretion of the Sponsor.
Available for what types of analyses?
To achieve the aims of the approved proposal.
How or where can data be obtained?
Access subject to approvals by Sponsor. Email or phone principal investigator.
Contact details:
Dr Gabby Shortt
Medical Research Institute of New Zealand
Postal Address:
Private Bag 7902, Wellington 6242
Physical Address:
Level 7, CSB Building
Wellington Hospital
Riddiford St, Newtown
Wellington 6021
New Zealand
Telephone: +64 4 805 0261
Email: gabby.shortt@mrinz.ac.nz


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.