Safety and Immunogenicity Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime Boost Regimen for the Prevention of Coronavirus Disease 2019 (COVID-19)

NCT04760730 | Completed Phase 1

• 1 other identifier: CV03872091
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II, parallel group, single blinded (participant blinded), randomised study assessing the immunogenicity and safety of AZD1222 and rAd26-S administered as heterologous prime-boost in alternating order in 2 study groups for the Prevention of COVID-19.

Conditions

COVID-19

Keywords

SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; 2019-nCoV; 2019 novel coronavirus; Respiratory disease; lung disease; COVID-19 Pandemic; coronavirus

Outcome Measures

Primary Outcomes (1)

• Antibody seroconversion rate (≥ 4 fold increase from baseline) against SARS-CoV-2 Spike protein 29 days post second vaccination

  The proportion of participants with post treatment seroresponse (defined as ≥ 4-fold rise in titres from Day 1 baseline value) to S antigen 29 days post second vaccination.

  Day 57

Secondary Outcomes (11)

• Incidence of local and systemic solicited Adverse Events (AEs) for 7 days following each vaccination

  from Day 1 till Day 7 and from Day 29 till Day 35

• Incidence of unsolicited AEs, Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) through 29 days post each vaccination

  from day 1 till Day 29 and from Day 29 till Day 57

• Antibody seroconversion rate (≥ 4 fold increase from baseline) against SARS-CoV-2 Spike protein 29 days post first vaccination

  Day 29

• Antibody seroconversion rate (≥ 4 fold increase from baseline) against Receptor Binding Domain (RBD) antigen

  Day 29, Day 57

• Сhange from baseline Geometric Mean Titre (GMT) of immunogenicity against Spike and RBD antigens at Day 15, 29, 57, 180.

  Day 1, Day 15, Day 29, Day 57, Day 180

Study Arms (2)

Group A: 1 intramuscular (IM) injection of AZD1222 on Day 1 followed by rAd26-S on Day 29

EXPERIMENTAL

Subjects will receive 1 intramuscular (IM) injection of 5 × 10\^10 viral particles (vp) (nominal) of AZD1222 on Day 1 followed by rAd26-S (1.0±0.5) х 10\^11 viral particles (vp) (nominal) on Day 29

Biological: AZD1222; Biological: rAd26-S

Group B: 1 intramuscular (IM) injection of rAd26-S on Day 1 followed by AZD1222 on Day 29

EXPERIMENTAL

Subjects will receive 1 intramuscular (IM) injection of rAd26-S (1.0±0.5) х 10\^11 viral particles (vp) (nominal) on Day 1 followed by AZD1222 5 × 10\^10 vp (nominal) on Day 29.

Biological: AZD1222; Biological: rAd26-S

Interventions

AZD1222 BIOLOGICAL

Active substance: ChAdOx1 nCoV-19, a replicant-deficient simian adenoviral vector in the amount of 5 х 10\^10 particles (nominal) per dose (unit dose strength \> 0.7 × 10\^11 vp/mL). Solution for intramuscular injection, supplied in vials in a carton box

Also known as: ChAdOx1 nCoV-19

Group A: 1 intramuscular (IM) injection of AZD1222 on Day 1 followed by rAd26-S on Day 29; Group B: 1 intramuscular (IM) injection of rAd26-S on Day 1 followed by AZD1222 on Day 29

rAd26-S BIOLOGICAL

Component I (Dose 1) - (0.5 ml per dose) contains: Active substance: recombinant adenovirus serotype 26 particles containing the SARS-CoV-2 protein S gene, in the amount of (1.0±0.5) х 10\^11 particles per dose (unit dose strength 1 × 10\^11 vp/0.5 mL) . Solution for intramuscular injection, supplied in vials in containers

Also known as: Gam-COVID-Vac combined vector vaccine

Group A: 1 intramuscular (IM) injection of AZD1222 on Day 1 followed by rAd26-S on Day 29; Group B: 1 intramuscular (IM) injection of rAd26-S on Day 1 followed by AZD1222 on Day 29

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all of the following criteria apply:
• Participants are:
• Overtly healthy as determined by medical evaluation, or
• Medically stable such that, according to the judgment of the investigator, hospitalisation within the study period is not anticipated and the participant appears likely to be able to remain in follow-up through the end of protocol-specified follow up.
• (A stable medical condition is defined as disease not requiring significant change in therapy or hospitalisation for worsening disease during the 3 months prior to enrolment.)
• Able to understand and comply with study requirements/procedures based on the assessment of the investigator.
• Female participants
• Women of childbearing potential must:
• Have a negative pregnancy test on the day of screening and on Day 1
• Use one highly effective form of birth control for at least 28 days prior to Day 1 and agree to continue using one highly effective form of birth control through 60 days following administration of the second dose of study vaccine. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Periodic abstinence, the rhythm method, and withdrawal are NOT acceptable methods of contraception.
• Women are considered of childbearing potential unless they meet either of the following criteria:
• Surgically sterilised (including bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or
• Postmenopausal
• For women aged \< 50 years, postmenopausal is defined as having both:
• A history of ≥ 12 months amenorrhea prior to first dosing, without an alternative cause, following cessation of exogenous sex-hormonal treatment, and

You may not qualify if:

• Known past laboratory-confirmed SARS-CoV-2 infection less than 6 month prior to screening (the date of diagnosis must be confirmed by an official document).
• Positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) test at screening.
• Significant infection or other illness, including fever \> 37.8°C on the day prior to or day of randomisation.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including human immunodeficiency virus (HIV) infection; asplenia; recurrent severe infections and use of chronic immunosuppressant medication within the past 6 months (≥ 20 mg/day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to vaccination), except topical/inhaled steroids or short term oral steroids (course lasting ≤ 14 days).
• Note: HIV-positive participants with CD4 counts \> 500 for ≥ 12 months and on a stable HIV antiretroviral regimen may be enrolled.
• Note: Topical tacrolimus is allowed if not used within 14 days prior to the day of enrolment.
• History of allergy to any component of the vaccine.
• Any history of anaphylaxis or angioedema.
• Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and uterine cervical carcinoma in situ).
• History of serious psychiatric condition likely to affect participation in the study.
• Bleeding disorder (eg, factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
• Suspected or known current alcohol or drug dependency.
• History of Guillain-Barré syndrome or any other demyelinating condition.
• Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed).

Sponsors & Collaborators

• R-Pharm: lead
• AstraZeneca: collaborator

Study Sites (1)

Tawam Hospital

Al Ain City, 15258, United Arab Emirates

Location

MeSH Terms

Conditions

COVID-19; Respiration Disorders; Lung Diseases; Coronavirus Infections

Interventions

ChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines

Study Officials

• Mikhail Samsonov

  Chief Medical Officer, R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: single-blinded (participant-blinded study)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 18, 2021
• Study Start: July 13, 2021
• Primary Completion: March 29, 2022
• Study Completion: July 26, 2022
• Last Updated: October 26, 2022

Record last verified: 2022-10

Locations

AE (1)