Overview

The study GPPAD-05 AVAnT1A is a phase 4 clinical trial intending to enroll 2252 children, who will be randomly assigned to receive COVID-19 vaccination (Comirnaty® 3 μg Omicron XBB.1.5 or new variant Comirnaty vaccines ) or placebo from age 6 months.

The study is an investigator initiated, randomized, controlled, multicentre, multinational, primary prevention trial for children at increased risk of type 1 diabetes.

The primary objective is to determine whether vaccination of children with elevated genetic risk for type 1 diabetes against COVID-19 from 6 months of age reduces the cumulative incidence of islet autoantibodies or type 1 diabetes in childhood.

Secondary objectives are:

1. to determine whether vaccination against COVID-19 similarly reduces the cumulative incidence of multiple islet autoantibodies in childhood.
2. to determine whether vaccination against COVID-19 similarly reduces the cumulative incidence of type 1 diabetes in childhood and
3. to determine whether vaccination against COVID-19 similarly reduces the cumulative incidence of celiac disease-associated transglutaminase autoantibodies in childhood.

Further exploratory objectives are described in the study protocol.

Study participants will be identified through an ongoing study screening for genetic risk of type 1 diabetes using a polygenic risk score (NCT03316261).

Eligible participants will be enrolled at age 3.00 to 4.00 months (baseline visit).

Randomization to vaccine or placebo will occur at age 6.00 to 7.00 months at visit 2. Consent will be obtained by the custodial parents prior to enrollment.

Eligibility

Inclusion Criteria:

1. Ages between 3.00 and 4.00 months at the time of enrollment.
2. A high genetic risk (>10%) to develop islet autoantibodies by age 6 years as determined by a HLA DR/DQ genotype, polygenic risk score and first-degree family history of type 1 diabetes status.
3. Written informed consent signed by the custodial parent(s).

Exclusion Criteria:

1. Previous hypersensitivity to the excipients of the vaccine.
2. Any medical condition, concomitant disease or treatment that may interfere with the assessments or may jeopardize the participant's safe participation in the study. These include immune deficiencies, and conditions or treatments that lead to immune suppression.
3. Likely poor compliance due to expected change in residency.
4. Diagnosis of diabetes prior to recruitment or randomisation
5. Current use of any other investigational drug