COVID-19 Vaccination of Immunodeficient Persons (COVAXID) (COVAXID)

• ClinicalTrials.gov Identifier: NCT04780659
• Recruitment Status: Active, not recruiting
• First Posted: March 3, 2021
• Last Update Posted: September 9, 2021
• Sponsor: Karolinska University Hospital
• Collaborator: Karolinska Institutet
• Information provided by (Responsible Party): Soo Aleman, Karolinska Institutet

Tracking Information

• First Submitted Date: February 19, 2021
• First Posted Date: March 3, 2021
• Last Update Posted Date: September 9, 2021
• Actual Study Start Date: February 23, 2021
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 2, 2021)

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. [ Time Frame: 2 weeks after second dose of vaccine. ]

Proportion (95% confidence interval, CI) seroconverting to positive response to SARS-CoV-2 IgG serology test after two doses of vaccine, measured 2 weeks after second dose of vaccine.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 2, 2021)

• Assessment of any Adverse Events (AE) of the given vaccine [Safety and tolerability]. [ Time Frame: Duration of 0-14 days after each given vaccine dose. ]
  Proportion (95% CI) of study objects experiencing AE including reactogenicity, Serious Adverse Events (SAE), and Suspected Unexpected Serious Adverse Reaction (SUSAR).
• Frequency of SARS-CoV-2 infection documented by positive polymerase chain reaction (PCR) test. [ Time Frame: Day 0 - 6 months. ]
  Proportion (95% CI) of study objects with SARS-CoV-2 infection.
• Assessment of humoral and cellular immune responses in blood and saliva. [ Time Frame: Day 0- 6 months. ]
  Description of humoral and cellular immune responses in blood and saliva at baseline, and at time points day 0 (first vaccine dose), day 10 after first dose, day 21 (second vaccine dose), and 2 weeks, 3 months and 6 months after the second vaccine dose.
• Assessment of escape mutations of sequencing SARS-CoV-2 at breakthrough infection. [ Time Frame: Day 0-6 months. ]
  Genomic sequencing of SARS-CoV-2 at breakthrough infection.
• Assessment of graft versus host disease in allogenic stem cell transplanted persons after given vaccine. [ Time Frame: Day 0-6 months. ]
  Number of occurrence or worsening of graft versus host disease in allogenic stem cell transplanted persons after given vaccine will be described.
• Assessment of biopsy verified rejection in solid organ transplanted persons after given vaccine. [ Time Frame: Day 0-6 months. ]
  Number of occurrence of biopsy verified rejection in solid organ transplanted persons after given vaccine.
• Assessment of viremia, defined as HIV ribonucleic acid (RNA) > 50 copies/milliliter after vaccination in HIV infected persons. [ Time Frame: Day 0-6 months. ]
  Number of HIV infected persons with HIV ribonucleic acid (RNA) > 50 copies/milliliter after vaccination.
• Assessment of HIV deoxyribonucleic acid (DNA) levels after given vaccine in HIV infected persons. [ Time Frame: Day 0-6 months. ]
  HIV DNA levels at baseline, and 3 and 6 months after second dose of vaccine.
• Assessment of oral and gut microbiota in immunosuppressed and controls, in relation to immune response to vaccination. [ Time Frame: Day 0-6 months. ]
  Description of oral and fecal microbiota at baseline and association to immune responses.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Covid19

Intervention

Biological: Comirnaty (COVID-19, mRNA vaccine)

Comirnaty will be administered two times, one at Day 0 and the second dose at Day 21.

Other Names:

• tozinameran
• Pfizer mRNA vaccine

Study Arms

Experimental: Vaccination with Comirnaty according to standard of care treatment

All study participants will receive Comirnaty according to current approval.

Intervention: Biological: Comirnaty (COVID-19, mRNA vaccine)

Publications *

• 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.
• 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 (N Y). 2022 Feb 11;3(2):137-153.e3. doi: 10.1016/j.medj.2022.01.001. Epub 2022 Jan 20.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 2, 2021): 540
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT04780659
• Other Study ID Numbers: 2021-000175-37
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Will submit data to European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) and share data result. Will share research results and data through national COVID-19 data portal, operated by SciLifeLab Data Centre, Sweden.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Within one year after study end.
• Access Criteria: Published in EudraCT and national COVID-19 data portal (SciLifeLab Data Centre)
• URL: https://eudract.ema.europa.eu/index.html

• Current Responsible Party: Soo Aleman, Karolinska Institutet
• Original Responsible Party: Same as current
• Current Study Sponsor: Karolinska University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Karolinska Institutet

Investigators

• Principal Investigator: Soo Aleman, MD, PhD; Karolinska University Hospital, ME Infectious Diseases

• PRS Account: Karolinska University Hospital
• Verification Date: September 2021