Clinical trial NCT04780659: COVID-19 Vaccination of Immunodeficient Persons (COVAXID)
Official title: Immunological Responses After Vaccination for COVID-19 With the Messenger Ribonucleic Acid (mRNA) Vaccine Comirnaty in Immunosuppressed and Immunocompetent Individuals. An Open and Non-randomized, Phase IV Multicenter Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Covid19
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
First posted: 2021-03-03
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The study is designed as an open, non-randomized, phase IV cohort study in which the mRNA vaccine Comirnaty will be given in two doses. Analyses will be performed on blood and saliva, investigating humoral and cellular vaccine responses. Occurence of local or systemic reactogenicity will be evaluated, as well as adverse events. The study will include persons with primary or secondary immunosuppressive disorders, as well as immunocompetent persons, with the aim of investigating if the immune responses after given Comirnaty mRNA vaccine against COVID-19.

Detailed description: In this study with 450 patients with primary or secondary immunosuppressive disorders (patients with primary immunodeficiency, HIV infected patients, patients with allogenic stem cell transplantation/CAR T cell treated, solid organ transplanted, and patients with chronic lymphatic leukemia) from Karolinska University Hospital, and healthy controls of 90 individuals for comparison, we will investigate the safety and the immune responses after mRNA vaccination with Comirnaty after two doses, under 6 months of time for each participant. The study is In collaboration with research groups at Karolinska Institutet and SciLifeLab, with planned in-depth detailed analyses of antibody responses as well as cellular responses. The study has obtained permission from Swedish Medical Agency and Swedish Ethical Review Authority.

Eligibility criteria: Inclusion Criteria:

1. Individuals ≥18 years old

2a. In the opinion of the investigator, individuals with immunosuppressive disease who meet one of the following criteria:

* Primary immunodeficiency
* Human immunodeficiency virus (HIV)-infection
* Allogeneic stem cell transplantation / Chimeric antigen receptor (CAR T cell) therapy
* Solid organ transplant
* Chronic lymphatic leukemia

or

2b. In the opinion of the investigator, individuals without immunosuppressive disease or treatment without significant co-morbidity

3. Provision of signed informed consent to participate in the study

Exclusion Criteria:

1. Previous or ongoing Coronavirus Disease-19 (COVID-19).
2. Coagulation disorders, other conditions associated with prolonged bleeding time or anticoagulant treatments, which according to the investigator contraindicate intramuscular injection. Conditions which can be corrected with measures such as platelet concentrate treatments, coagulation factors or other measures for people responsible for anticoagulants are not exclusion criteria.
3. Planned to receive another vaccine within 14 days before the first dose of the study vaccine, or during the period from the first dose of the study vaccine up to 14 days after the second dose of the study vaccine, and vaccination with another vaccine which in the investigator's opinion cannot be planned outside these time periods
4. Pregnancy or breast feeding.
5. Hypersensitivity to the active substance or to any of the excipients contained in the vaccine
6. Individuals who cannot understand the informed consent.
7. Individuals who for other reasons are considered by investigators as not suitable for inclusion

Primary outcomes:
measure: Assessment of seroconversion, defined as development of immunoglobulin G (IgG) antibodies against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) after vaccination of 2 doses in seronegative individuals.
timeFrame: 2 weeks after second dose of vaccine.
Secondary outcomes:
measure: Assessment of any Adverse Events (AE) of the given vaccine [Safety and tolerability].
timeFrame: Duration of 0-14 days after each given vaccine dose.
measure: Frequency of SARS-CoV-2 infection documented by positive polymerase chain reaction (PCR) test.
timeFrame: Day 0 - 6 months.
measure: Assessment of humoral and cellular immune responses in blood and saliva.
timeFrame: Day 0- 6 months.
measure: Assessment of escape mutations of sequencing SARS-CoV-2 at breakthrough infection.
timeFrame: Day 0-6 months.
measure: Assessment of graft versus host disease in allogenic stem cell transplanted persons after given vaccine.
timeFrame: Day 0-6 months.
measure: Assessment of biopsy verified rejection in solid organ transplanted persons after given vaccine.
timeFrame: Day 0-6 months.
measure: Assessment of viremia, defined as HIV ribonucleic acid (RNA) > 50 copies/milliliter after vaccination in HIV infected persons.
timeFrame: Day 0-6 months.
measure: Assessment of HIV deoxyribonucleic acid (DNA) levels after given vaccine in HIV infected persons.
timeFrame: Day 0-6 months.
measure: Assessment of oral and gut microbiota in immunosuppressed and controls, in relation to immune response to vaccination.
timeFrame: Day 0-6 months.
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
state: Huddinge
Study officials:
affiliation: Karolinska University Hospital, ME Infectious Diseases
name: Soo Aleman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cuapio A, Boulouis C, Filipovic I, Wullimann D, Kammann T, Parrot T, Chen P, Akber M, Gao Y, Hammer Q, Strunz B, Perez Potti A, Rivera Ballesteros O, Lange J, Muvva JR, Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Soderdahl G, Osterborg A, Smith CIE, Bogdanovic G, Muschiol S, Hellgren F, Lore K, Sobkowiak MJ, Gabarrini G, Healy K, Sallberg Chen M, Alici E, Bjorkstrom NK, Buggert M, Ljungman P, Sandberg JK, Aleman S, Ljunggren HG. NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals. Mol Med. 2022 Feb 8;28(1):20. doi: 10.1186/s10020-022-00443-2.
citation: Healy K, Pin E, Chen P, Soderdahl G, Nowak P, Mielke S, Hansson L, Bergman P, Smith CIE, Ljungman P, Valentini D, Blennow O, Osterborg A, Gabarrini G, Al-Manei K, Alkharaan H, Sobkowiak MJ, Yousef J, Mravinacova S, Cuapio A, Xu X, Akber M, Lore K, Hellstrom C, Muschiol S, Bogdanovic G, Buggert M, Ljunggren HG, Hober S, Nilsson P, Aleman S, Sallberg Chen M. Salivary IgG to SARS-CoV-2 indicates seroconversion and correlates to serum neutralization in mRNA-vaccinated immunocompromised individuals. Med. 2022 Feb 11;3(2):137-153.e3. doi: 10.1016/j.medj.2022.01.001. Epub 2022 Jan 20.