Clinical trial NCT05057897: A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults
Official title: A Phase IV Open-Label, Non-Randomized, Multi-Cohort, Multicenter Study in Previously Unvaccinated Immunocompromised Adults to Determine the Immunogenicity and Safety of AZD1222 Vaccine for the Prevention of COVID-19
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: COVID-19, SARS-CoV-2
Keywords: COVID-19 Vaccine
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-09-27
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Previously unvaccinated immunocompromised adults will be enrolled in 5 disease cohorts of approximately 60 participants each:

1. Solid organ transplant
2. Hematopoietic stem cell transplant
3. Solid organ cancer patients receiving cytotoxic chemotherapy
4. Chronic inflammatory disorders
5. Primary immunodeficiency A sixth cohort of immunocompetent individuals will also be recruited. Participants will be allocated to the immunocompromised cohorts according to the underlying aetiology of their immunocompromised status.

Immunocompromised participants will receive a third dose (primary vaccination series) 4 weeks or more after dose 2 with AZD1222 and will continue to be followed to the end of the study. Immunocompetent participants will be eligible to receive a third dose booster 6 months after dose 1 and will continue to be followed to the end of the study.
Primary purpose: PREVENTION

Brief summary: The aim of this study is to assess the immunogenicity and safety of AZD1222 for prevention of COVID-19 in immunocompromised adults.

Detailed description: The purpose of this study is to demonstrate the immunogenicity and safety of AZD1222, AstraZeneca's approved ChAdOx1 vector vaccine against SARS-CoV-2, in SARS-CoV-2 seronegative immunocompromised individuals who are unvaccinated.

Eligibility criteria: Inclusion Criteria:

1. Adult, ≥ 18 years at the time of signing the informed consent.
2. Cohort specific inclusion criteria:

Solid organ transplant

* Participants with heart, lung, kidney, or liver transplant, and are stable on immunosuppressants (defined as no change in dose in the previous 4 weeks).

Hematopoietic stem cell transplant

* Participants with autologous (up to 6 months after transplantation) or allogeneic stem cell transplant who are immunosuppressed, with no evidence of active graft-versushost disease, at least one month after the procedure.

Cancer patients on chemotherapy

* Participants with solid tumors (except breast cancer), histologically diagnosed, who were undergoing intravenous cytotoxic chemotherapy within the last 6 months, who received at least 1 cycle prior to cytotoxic chemotherapy, and have a life expectancy of longer than 3 months.

Chronic inflammatory conditions

* Participants with chronic inflammatory conditions, including those on immunosuppressant medications, can be recruited. The following conditions are specifically excluded: multiple sclerosis and peripheral demyelinating disease.

Primary immune deficiency

* Examples include combined granulomatous disorder, SCID, common variable immunodeficiency.

Immunocompetent:

* No confirmed or suspected immunosuppressive or immunodeficient state.
* No use of immunosuppressant medication within the past 1 month (≥ 20 mg per day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to administration of AZD1222). The following exceptions are permitted: topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days).
* No receipt of immunoglobulins and/or any blood products within 3 months prior to administration of AZD1222 or expected receipt during the period of study follow up.
* No severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness, as judged by the Investigator.

Exclusion Criteria:

1. History of allergic disease or reactions likely to be exacerbated by any component of AZD1222.
2. Active infection with SARS-CoV-2 as confirmed locally by nucleic acid amplification test (e.g. RT-PCR).
3. Known current or past laboratory-confirmed SARS-CoV-2 infection.
4. Significant infection or other acute illness, including fever (temperature \> 37.8°C) on the day prior to or day of first dosing.
5. Thrombocytopenia with platelet count ≤ 75,000 x 109/microliter based on complete blood count test at screening visit.
6. HIV-positive participants based on a positive ELISA test performed at screening visit.
7. History of cerebral venous sinus thrombosis (CVST).
8. Receipt of any vaccine (licensed or investigational) within 30 days prior to and after administration of AZD1222.

Primary outcomes:
measure: Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Days 29 and 57
measure: Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Days 29 and 57
measure: GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay
timeFrame: Days 29 and 57
measure: Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay
timeFrame: Days 29 and 57
Secondary outcomes:
measure: GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Day 57
measure: Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Day 57
measure: GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay
timeFrame: Day 57
measure: Percentage of Participants With Seroresponse to SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay
timeFrame: Day 57
measure: GMT for SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
measure: Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay
timeFrame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
measure: GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay
timeFrame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
measure: Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay
timeFrame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
Study officials:
References: