Clinical trial NCT05158829: COVID-19 Antibody Responses In Cystic Fibrosis
Official title: COVID-19 Antibody Responses In Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cystic Fibrosis
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
First posted: 2021-12-15
Enrollment: 250
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consenting people with cystic fibrosis of any age, genotype, transplant status and disease severity will be eligible to participate in the study. The study population is expected to be representative of the general CF population.

Brief summary: Coronavirus disease 2019 (COVID-19) which is caused by the virus Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in an ongoing global pandemic. It is unclear whether the relatively low number of reported cases of COVID-19 in people with CF (pwCF) is due to enhanced infection prevention practices or whether pwCF have protective genetic/immune factors. This study aims to prospectively assess the proportion of pwCF, including both adults and children with CF who have evidence of SARS-CoV-2 antibodies over a two-year period. This study will also examine whether pwCF who have antibodies for SARS-CoV-2 have a different clinical presentation and what impact this has on their CF disease. The proposed study will recruit pwCF from paediatric and adult CF centres throughout the United Kingdom. Serological testing to detect antibodies will be performed on blood samples taken at month 0, 6, 12, 18 and 24 with additional time-points if bloodwork is available via normal clinical care. Clinical data on, lung function, CF-related medical history, pulmonary exacerbations, antibiotic use, and microbiology and vaccination receipt, will be collected during routine clinical assessments.

Associations will be examined between socio-demographic and clinical variables and serologic testing. The investigators will also examine the effects of SARS-CoV-2 infection on clinical outcomes and analyse end-points to explore any age-related or gender-based differences, as well as subgroup analysis of outcomes in lung-transplant recipients and pwCF receiving cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies. As pwCF receive COVID-19 vaccination the investigators will perform a comparison of the development and progression of anti-SARS-CoV-2 antibodies in pwCF following natural infection and vaccination SARS-CoV-2 over time.

Detailed description: This is a prospective, longitudinal cohort study in people with Cystic Fibrosis (pwCF) that involves repeated serial sampling of participants. This study design was chosen to provide comprehensive information on SARS-CoV-2 seroprevalence changes over time and the subsequent clinical impact on pwCF. The study will be conducted at participating CF centres over a 3-year period. Study participants will include paediatric and adult pwCF. Participating investigators can enrol all eligible pwCF over a 12-month period. Participants are then followed up for 24 months. Participants will donate blood samples at their routine clinic visits. Blood samples will be collected at Day 0 (baseline), at Months 6, 12, 18 and 24 (to coincide with routine clinical reviews). Additional blood samples will be taken opportunistically every time the participant visits the clinic for blood draws. These blood samples could be related to, routine care, annual review visits, pulmonary exacerbations (PEx), CF complications or when initiating new treatments (e.g. CFTR modulators).

Serum from blood samples will be shipped to a central laboratory (Queen's University Belfast) for standardized measurement of SARS-CoV-2 antibodies.

Alongside the blood samples the investigator will also collect clinical data from the patient's health records and will input this data into the case report form (CRF). Clinical data will be collected in conjunction with routine care visits, according to local clinical practice. Investigators will collect data elements from information routinely recorded in the patients' medical records. Data will be collected at baseline, month 6, 12, 18 and 24 as per the study schedule, and at additional blood sampling timepoints as previously explained above. Data collection will include routine data available from CF clinic follow-ups including background demographic information, CF medical history, medications, exacerbation information, sputum microbiology and clinical and lung function parameters. Information on SARS-CoV-2 infection history and vaccine receipt will also be collected.

The maximum follow-up duration of participation in the study for each patient will be 24 months. This study duration (24-month follow-up) is justified as it provides sufficient time to observe changes in antibody prevalence over the course of the COVID-19 pandemic as well as sufficient time to determine long term clinical outcomes for pwCF who are SARS-CoV-2 seropositive. Furthermore, the investigators anticipate the 2-year study follow-up period will provide sufficient time to observe the impact of vaccination on antibody levels given that a number of vaccines are now commercially available.

The investigators will compare the level of antibody responses between natural COVID-19 infection and vaccination in pwCF and how this varies over time. This will be achieved by analyzing seroprevalence and antibody levels according to natural infection and vaccination status and according to time of sample post infection or post vaccination, if known.

Optional Study sample collection:

For participants who consent, a second blood sample will also be drawn into Ethylenediamine tetraacetic acid (EDTA) tubes (plasma). Consent to this optional study sample would allow this sample and any remaining serum (following antibody testing) to be stored for future analysis and allow further research to be carried out on related studies to COVID-19 and CF.

Eligibility criteria: Inclusion Criteria:

* Consenting people with cystic fibrosis of any age, genotype, transplant status and disease severity

Exclusion Criteria:

* Refusal to give informed consent
* Contraindication to venepuncture. Participants already enrolled in a clinical trial are eligible for enrollment in this study. Inclusion in CAR-CF should not preclude enrollment in other observational clinical trial studies or clinical trials of an investigational medicinal product (CTIMP).

Primary outcomes:
measure: To evaluate SARS-CoV-2 seroprevalence
timeFrame: 3-year period (comprising a 1-year enrollment period and a 2-year follow-up)
measure: Association of SARS-CoV-2 seropositivity, clinical symptoms and clinical outcomes in pwCF
timeFrame: 3-year period (comprising a 1-year enrollment period and a 2-year follow-up)
measure: Longitudinal comparison of the detection, including level and duration, of anti-SARS-CoV-2 antibodies in pwCF following natural infection and SARS-CoV-2 vaccination.
timeFrame: 3-year period (comprising a 1-year enrollment period and a 2-year follow-up)
Secondary outcomes:
measure: Storage of samples for future analysis
timeFrame: anticipated 5-10 years
Other outcomes:
Locations:
city: Firenze
country: Italy
facility: Centro Regionale toscano di riferimento per la fibrosi cistica- Azienda Ospedaliero- universitaria Mayer
city: Genova
country: Italy
facility: Istituto G. Gaslini Centro Fibrosis Cistica
city: Milan
country: Italy
facility: UOS Fibrosi Cistica dell'Adulto, Fondazione IRCCS Ca' Granda Ospedale Policlinico
city: Orbassano
country: Italy
facility: Centro Regionale per la Fibrosi Cistica Azienda Ospedaliero-Universitaria San Luigi Gonzaga
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesù di Roma Divisione Dipartimento di Pediatria
city: Torino
country: Italy
facility: Centro Regionale per la Fibrosi Cistica Piemonte-Torino Sezione Infantile presso AOU Città della Salute e della Scienza
Study officials:
affiliation: Milan CF Center, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico
name: Carla Colombo, MD
role: PRINCIPAL_INVESTIGATOR
References: