A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults

Study Overview
=================
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.

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

Conditions
-----------------
COVID-19, SARS-CoV-2

Intervention / Treatment
-----------------
* Biological: AZD1222


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult, ≥ 18 years at the time of signing the informed consent. 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: History of allergic disease or reactions likely to be exacerbated by any component of AZD1222. Active infection with SARS-CoV-2 as confirmed locally by nucleic acid amplification test (e.g. RT-PCR). Known current or past laboratory-confirmed SARS-CoV-2 infection. Significant infection or other acute illness, including fever (temperature > 37.8°C) on the day prior to or day of first dosing. Thrombocytopenia with platelet count ≤ 75,000 x 109/microliter based on complete blood count test at screening visit. HIV-positive participants based on a positive ELISA test performed at screening visit. History of cerebral venous sinus thrombosis (CVST). Receipt of any vaccine (licensed or investigational) within 30 days prior to and after administration of AZD1222.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Previously unvaccinated immunocompromised adults will be enrolled in 5 disease cohorts of approximately 60 participants each: Solid organ transplant Hematopoietic stem cell transplant Solid organ cancer patients receiving cytotoxic chemotherapy Chronic inflammatory disorders 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1 - immunocompromised participants with solid organ transplant<br>Previously unvaccinated immunocompromised participants with solid organ transplant will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2. | Biological: AZD1222<br>* 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6<br>|
| Other: Cohort 2 - immunocompromised participants with hematopoietic stem cell transplant<br>Previously unvaccinated immunocompromised participants with hematopoietic stem cell transplant will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2. | Biological: AZD1222<br>* 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6<br>|
| Other: Cohort 3 - immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy<br>Previously unvaccinated immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2. | Biological: AZD1222<br>* 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6<br>|
| Other: Cohort 4 - immunocompromised participants with chronic inflammatory disorders<br>Previously unvaccinated immunocompromised participants with chronic inflammatory disorders will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2. | Biological: AZD1222<br>* 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6<br>|
| Other: Cohort 5 - immunocompromised participants with primary immunodeficiency<br>Previously unvaccinated immunocompromised participants with primary immunodeficiency will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2. | Biological: AZD1222<br>* 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6<br>|
| Other: Cohort 6 - immunocompetent participants<br>Previously unvaccinated immunocompetent participants will receive a primary vaccination series with 2 IM doses of AZD1222 separated by 4 weeks, followed by a booster dose of AZD1222 administered 6 months after the first dose. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1. Participants will receive a third dose booster 6 months after dose 1 and will continue to be followed to the end of the study. | Biological: AZD1222<br>* 10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 specific titres in SARS-CoV-2 naïve immunocompromised adults and immunocompetent adults ≥ 18 years | Characterization of immunogenicity of a 2-dose primary vaccination with AZD1222 with a 4-week dosing interval | 28 days after dosing | 
| Seroresponse of SARS-CoV-2 specific titres (≥ 4-fold rise in titres from baseline) in SARS-CoV-2 naïve immunocompromised adults and immunocompetent adults ≥ 18 years | Characterization of immunogenicity of a 2-dose primary vaccination with AZD1222 with a 4-week dosing interval | 28 days after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of SARS-CoV-2 specific GMT titres in adults ≥ 18 years with a 4-week dosing interval between SARS-CoV-2 naïve participants with any immunocompromised condition compared to immunocompetent participants | Description of the immunogenicity of a 2-dose primary vaccination with AZD1222 | 28 days after Dose 2 | 
| Difference in seroresponse rates of SARS-CoV-2 specific titres in adults ≥ 18 years with a 4-week dosing interval between SARS-CoV-2 naïve participants with any immunocompromised condition compared to immunocompetent participants | Description of the immunogenicity of a 2-dose primary vaccination with AZD1222, with a difference of ≥ 4-fold rise in titres from baseline | 28 days after Dose 2 | 
| Incidence of local and systemic solicited AEs after dosing in SARS-CoV-2 naïve immunocompromised adults ≥ 18 years | Characterization of the reactogenicity and safety of a 3-dose primary vaccination series with AZD1222 with a 4-week dosing interval | For 7 days after each dose of AZD1222 | 
| Incidence of unsolicited AEs after dosing in SARS-CoV-2 naïve immunocompromised adults ≥ 18 years | Characterization of the reactogenicity and safety of a 3-dose primary vaccination series with AZD1222 with a 4-week dosing interval | For 28 days post dose after each vaccination (i.e., until Day 29 following the first vaccination and Day 57 following the second vaccination) and Day 85 following the 3rd vaccination | 
| Incidence of SAEs, MAAEs and AESIs in SARS-CoV-2 naïve immunocompromised adults ≥ 18 years | Characterization of the reactogenicity and safety of a 3-dose primary vaccination series with AZD1222 with a 4-week dosing interval | From Day 1 post treatment to the last study visit | 
| Absolute and change from baseline for safety laboratory measures in SARS-CoV-2 naïve immunocompromised adults ≥ 18 years | Characterization of the reactogenicity and safety of a 3-dose primary vaccination series with AZD1222 with a 4-week dosing interval | Through 28 days after 3rd dose | 
| Ratio of SARS-CoV-2 specific GMT titres in adults ≥ 18 years with a 4-week dosing interval between SARS-CoV-2 naïve participants in the comparator cohort as compared with immunocompetent participants | Description of the immunogenicity of a 2-dose primary vaccination with AZD1222 Comparator cohorts: solid organ transplant/hematopoietic stem cell transplant/solid organ cancer patients receiving cytotoxic chemotherapy/chronic inflammatory disorders/primary immunodeficiency | 28 days after Dose 2 | 
| Difference in seroresponse rates of SARS-CoV-2 specific titres in adults ≥ 18 years with a 4-week dosing interval between SARS-CoV-2 naïve participants in the comparator cohort as compared with immunocompetent participants | Description of the immunogenicity of a 2-dose primary vaccination with AZD1222, with a difference of ≥ 4-fold rise in titres from baseline Comparator cohorts: solid organ transplant/hematopoietic stem cell transplant/solid organ cancer patients receiving cytotoxic chemotherapy/chronic inflammatory disorders/primary immunodeficiency | 28 days after Dose 2 | 
| SARS-CoV-2 specific titres in immunocompromised adults ≥ 18 years | Characterization of immunogenicity after a 3rd-dose in a 3 dose primary vaccination series with AZD1222 | 28 days after Dose 3 | 
| Seroresponse of SARS-CoV-2 specific titres (≥ 4-fold rise in titres from baseline) in immunocompromised adults ≥ 18 years | Characterization of immunogenicity after a 3rd-dose in a 3 dose primary vaccination series with AZD1222 | 28 days after Dose 3 | 
| Ratio of SARS-CoV-2 specific GMT titres in adults ≥ 18 years between SARS-CoV-2 naïve immunocompromised participants compared to immunocompetent participants after a 2-dose primary vaccination | Description of immunogenicity after the 3rd dose in a 3-dose primary vaccination with AZD1222 Comparator cohort: Each of 5 immunocompromised cohorts and pooled immunocompromised cohorts Reference cohort: Immunocompetent | 28 days after Dose 3 (28 Days after Dose 2 for reference cohort) | 
| Difference in seroresponse rate of SARS-CoV-2 specific GMT titres in adults ≥ 18 years between SARS-CoV-2 naïve immunocompromised participants compared to immunocompetent participants after a 2-dose primary vaccination | Description of immunogenicity after the 3rd dose in a 3-dose primary vaccination with AZD1222 with a difference of ≥ 4-fold rise in titres from baseline Comparator cohort: Each of 5 immunocompromised cohorts and pooled immunocompromised cohorts Reference cohort: Immunocompetent | 28 days after Dose 3 (28 Days after Dose 2 for reference cohort) | 
| Ratio of SARS-CoV-2 specific GMT titres in adults ≥ 18 years between SARS-CoV-2 naïve immunocompromised and immunocompetent participants | Description of immunogenicity of the AZD1222 vaccination between 28 days post second dose compared to 28 days post third dose | 28 Days after Dose 2 and 28 Days after Dose 3 | 
| Difference in seroresponse rates of SARS-CoV-2 specific titres in adults ≥ 18 years between SARS-CoV-2 naïve immunocompromised and immunocompetent participants | Description of immunogenicity of the AZD1222 vaccination between 28 days post second dose compared to 28 days post third dose with a difference of ≥ 4 fold increase in titres from 28 days post dose 2 to 28 days post dose 3 | 28 Days after Dose 2 and 28 Days after Dose 3 | 
| SARS-CoV-2 specific titres in immunocompetent adults ≥ 18 years | Characterization of the immunogenicity after a third-dose booster vaccination of AZD1222, administered 6 months after dose 1 of a 2-dose primary vaccination with AZD1222 | 28 days after Dose 3 | 
| Seroresponse of SARS-CoV-2 specific titres (≥ 4-fold rise in titres from baseline) in immunocompetent adults ≥ 18 years | Characterization of the immunogenicity after a third-dose booster vaccination of AZD1222, administered 6 months after dose 1 of a 2-dose primary vaccination with AZD1222 | 28 days after Dose 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19 Vaccine