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      • abstract_of_study<div>\n Background: Malaria in pregnancy remains a substantial public health concern in endemic regions, with first-trimester infections being particularly harmful. The World Health Organization (WHO) now recommends artemether-lumefantrine (AL), an artemisinin-based combination therapy (ACT), as the first-line treatment for uncomplicated malaria in the first trimester of pregnancy, replacing quinine. This recommendation followed a comprehensive review of observational data on inadvertent first-trimester exposures from pregnancy exposure registries, which showed that initial concerns about the teratogenicity of artemisinin derivatives raised by preclinical studies and animal models did not apply to human pregnancies.</div>\n<div>\n Several other highly effective ACTs are used in sub-Saharan Africa, a trend likely to increase rapidly as part of WHO's multiple first-line strategies. Moreover, novel treatments that show promise against resistant strains and may potentially impede their emergence or spread could become available. SAFIRE aims to efficiently generate evidence on the safety and efficacy of antimalarials for treating uncomplicated malaria in the first trimester. Each of the antimalarials to be evaluated in this SAFIRE trial should meet the following criteria:</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Registered antimalarial product for the treatment of uncomplicated malaria or at minimum, confirmation of a favourable benefit/risk ratio for the treatment of uncomplicated malaria in a confirmatory Phase III program in children or adults with P. falciparum infection</div>\n<div>\n •<span style=\"white-space:pre\"> </span>No teratogenic concerns in preclinical studies</div>\n<div>\n In the case of antimalarials with a teratogenic signal in preclinical studies:</div>\n<div>\n •<span style=\"white-space:pre\"> </span>No significant safety concerns in women inadvertently treated with these drugs in the first trimester (from observational studies and/or pregnancy exposure registries), </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Ideally, no significant safety, tolerability and efficacy concerns in clinical trials during the second and third trimesters of pregnancy would be preferred.</div>\n<div>\n Justification: It took over two decades to accumulate sufficient evidence for WHO to recommend AL for use in the first trimester. There is an urgent need to expedite this process and provide informed guidance to health care providers and mothers on other potentially effective and safe antimalarials, especially in the context of the increased threat of resistance against AL. Furthermore, stringent regulatory authorities now encourage more research involving pregnant women.</div>\n<div>\n Objectives: The primary efficacy objective in the initial phase of this adaptive platform trial is to confirm the efficacy of alternative antimalarials in pregnant women in the first trimester with uncomplicated malaria by demonstrating non-inferiority to the current standard of care with AL. The key safety objective is to assess their non-inferiority compared with AL in terms of safety regarding pregnancy outcomes. </div>\n<div>\n Study design: SAFIRE is a multicentre, open-label, randomised, non-inferiority, adaptive platform trial (APT). The rationale for a non-inferiority approach is that if these newer drugs prove to be non-inferior to AL in terms of efficacy and safety, they offer secondary advantages such as longer post-treatment prophylaxis or simpler dosing regimens (once instead of twice daily for 3 days). These benefits could improve treatment adherence and effectiveness in real-world settings.</div>\n<div>\n The study employs a Bayesian adaptive design, allowing for interim analyses and potential early stopping for safety. The rule for making decisions during interim analysis is to stop enrolment to a new intervention arm if there is more than an 85% chance that the hazard ratio for the safety endpoint exceeds 1.1 (the non-inferiority margin) relative to the standard of care. These frequent interim analyses for safety will allow for the early stopping of the trial arm if safety concerns arise and enable more efficient use of resources and timely decision-making based on accumulating evidence.</div>\n<div>\n The adaptive platform trial design evaluates multiple interventions and uses a shared control group, reducing administrative burden and allowing efficient participant allocation. It provides a flexible framework for introducing new treatment arms, which is ideal for assessing multiple promising antimalarials for first-trimester use.</div>\n<div>\n SAFIRE is an open-ended trial that continuously evaluates new antimalarials without a set end date, adapting to emerging treatments and research priorities in malaria during pregnancy.</div>\n<div>\n The protocol uses a modular design with a master protocol outlining the overall framework and intervention-specific appendices (ISAs) for each antimalarial. This approach enables efficient addition or removal of treatment arms without full master protocol revision, enhancing flexibility and responsiveness.</div>\n<div>\n Methods: Pregnant women in their first trimester (≤13 weeks' gestation) with confirmed uncomplicated Plasmodium falciparum malaria will be randomly assigned to receive either the standard of care with artemether-lumefantrine (AL) or a newer antimalarial. The details of the newer antimalarials, corresponding sample sizes, and allocation ratio are described in ISAs. The primary efficacy endpoint is PCR-adjusted adequate clinical and parasitological response (ACPR) by day 42. The key safety endpoint is a composite of fetal loss or major congenital anomalies. Secondary efficacy endpoints include PCR-unadjusted cure rates (i.e, the cumulative rate  of women without recurrent malaria infection due to treatment failure or reinfection), serving as a proxy for the duration of post-treatment prophylaxis.</div>\n<div>\n Collaboration and funding: The initial phase of the study is co-sponsored by the Liverpool School of Tropical Medicine (LSTM) and the Medicines for Malaria Venture (MMV) and is funded by Global Health EDCTP3, the EU, UKRI, and SERI of the Swiss Confederation. As this is an open-ended platform trial, additional sponsors and funders may be added in the future as new treatment arms are incorporated. </div>\n<div>\n Ethical considerations and governance: The trial adheres to stringent ethical standards, including obtaining informed consent from all participants and providing close monitoring for adverse events. An independent Data Safety Monitoring Board will monitor the safety data as they accumulate with predefined stopping rules.</div>\n<div>\n Significance: SAFIRE is designed to inform WHO policy. By expanding the range of safe and effective treatment options, SAFIRE has the potential to improve the management of malaria in early pregnancy, an important period for the developing placenta and fetus, and contribute to better maternal and child health outcomes in endemic areas.</div>\n<div>\n  </div>\n
      • study_title<p>\n A multicentre open-label, non-inferiority adaptive platform randomised controlled trial to evaluate the efficacy, safety, and tolerability of antimalarials for the treatment of uncomplicated malaria in the first trimester of pregnancy</p>\n
      • laymans_summary<div>\n The SAFIRE study aims to find effective treatments with acceptable safety for malaria in early pregnancy, a particularly sensitive time for the adverse consequences of malaria in pregnancy for both mother and baby. Currently, WHO recommends the antimalarial drug artemether-lumefantrine (AL) for the treatment of uncomplicated malaria in the first trimester of pregnancy. Other promising treatments are being rolled out in malaria-endemic countries for use in adults and children and data on current exposures in the first trimester are limited and insufficient to support a recommendation.  This is due to the fact that pregnant women are often excluded from clinical trials to protect fetuses, unintentionally depriving them of newer, potentially better treatments. Instead, they often received older, less effective drugs. The International Council for Harmonisation (ICH E21) and stringent regulatory authorities (e.g. EMA, FDA and MHRA) now encourage pregnant women to be included in well-designed studies to ensure they can safely benefit from medical advances. </div>\n<div>\n This study will compare AL with the newer antimalarial drugs that have shown no significant safety concerns in laboratory studies, accidental use during early pregnancy, or trials in later pregnancy stages. The main goal is to see if these new drugs work as well as AL in treating malaria and are safe for the mother, her pregnancy and the developing baby. The newer antimalarials being tested also offer additional benefits to pregnant women, such as preventing new malaria infections for longer after treatment than the current standard treatment (AL). Also, they can be taken just once a day instead of twice daily, like AL. A simpler dosing schedule could improve adherence to the study medication, meaning women are more likely to take the full course of treatment as prescribed. This, in turn, enhances its effectiveness in real-world settings. Future antimalarials to be tested will include those with improved resistance profiles, offering more effective options for combating drug-resistant strains.</div>\n<div>\n SAFIRE uses a special “Bayesian Adaptive Platform Trial” (APT) design. This open-ended approach allows researchers to add new interventions under the same protocol, leveraging the existing trial network with infrastructure. The use of a common protocol with innovative adaptive statistical design allows the trial to stop early if it becomes clear that the new drugs are unsafe. APTs were commonly used in COVID-19 trials because they help researchers respond quickly to new information. This APT protocol uses a typical multi-part structure, including a “master protocol” that serves as the overall blueprint for the study, outlining the general design, core methods, and shared elements across all treatments being tested, followed by “Intervention-Specific Appendices (ISAs)”, providing detailed information about each specific antimalarial treatment being evaluated. ISAs can be easily added or removed as new treatments become available or as existing ones are found to be ineffective or unsafe. This flexible approach allows researchers to efficiently adapt the study as new information emerges without completely redesigning the entire trial each time a change is needed.</div>\n<div>\n This multi-centre trial will be conducted in several countries in Africa where malaria is very common. Women will be randomly assigned to receive either AL or one of the new treatments. Participants will be seen daily for 4 days, then weekly for 6 weeks to assess the response to treatment, and then monthly until delivery. Their health and outcomes will be closely monitored during and after pregnancy. Newborns will be followed for 6 months. An independent data safety and monitoring board (DSMB) will regularly monitor safety data as it accumulates. By finding more treatment options, this study could improve care for pregnant women with malaria and lead to better health for mothers and babies in areas where malaria is widespread. The results will help inform global health policies and potentially change how we treat malaria in early pregnancy.</div>\n<div>\n  </div>\n
      • short_titleSAFIRE
      • protocol_noECCT/25/05/12
      • version_no2.0
      • date_of_protocol20-03-2025
      • study_drugDihydroartemisinin-piperaquine, Pyronaridine-artesunate
      • disease_conditionMalaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameDihydroartemisinin-piperaquine, Pyronaridine-artesunate
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameArtemether-Lumefantrine (Lumiter)
      • comparator_registeredYes
      • comparator_countriesKanya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressruth.njoroge@ke.lstmed.ac.uk
      • applicant_covering_letter1
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      • declaration_applicantDr. Ruth Njoroge
      • declaration_date130-05-2025
      • declaration_principal_investigatorDr. Hellen Barsosio
      • declaration_date230-05-2025
      • placebo_presentNo
      • study_objectives<p>\n The primary efficacy objective in the initial phase of this adaptive platform trial is to confirm the efficacy of alternative antimalarials in pregnant women in the first trimester with uncomplicated malaria by demonstrating non-inferiority to the current standard of care with AL.</p>\n<p>\n The key safety objective is to assess their non-inferiority compared with AL in terms of safety regarding pregnancy outcomes. </p>\n
      • principal_inclusion_criteria<div>\n •<span style=\"white-space:pre\"> </span>≥2 weeks and <14 weeks (13-6/7 weeks inclusive) gestation from the last menstrual period (LMP) as assessed by echography </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Microscopy confirmed P. falciparum mono or mixed infections, regardless of symptoms. </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Emancipated minor and aged ≥16 years</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Haemoglobin ≥ 7 g/dL </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Residence within the health facility catchment area </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Willingness to adhere to study requirements and to deliver the baby at the local health facility </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Ability to provide written informed consent</div>\n
      • principal_exclusion_criteria<div>\n •<span style=\"white-space:pre\"> </span>Known allergy to any of the study drugs</div>\n<div>\n •<span style=\"white-space:pre\"> </span>History of known pregnancy complications or poor obstetric history, such as repeated miscarriages, stillbirths, or eclampsia</div>\n<div>\n •<span style=\"white-space:pre\"> </span>History or presence of major illnesses likely to influence pregnancy outcome; </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Known HIV positive</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Any significant illness at the time of screening requiring hospitalisation, including severe malaria</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Intent to move out of the study catchment area before delivery or planned delivery out of the catchment area</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Recent (2 weeks) treatment with antimalarials or antimicrobials with antimalarial activity (chloroquine, AL, DP, PA, SPAQ, ASAQ, MQAS, azithromycin, clindamycin, tetracycline, quinolones, cotrimoxazole and SP)</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Twin/multiple pregnancy detected</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Non-viable pregnancy confirmed by ultrasound or doppler</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Known history or evidence of clinically significant cardiovascular disorders or family history of sudden death or congenital long QT syndrome or current co-administration of other drugs that might contribute to a prolonged QTc interval or cause “Torsades de Point” </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Chronic medical condition requiring frequent medications (e.g., TB, suspected hepatic lesions, liver disease, sickle cell disease, diabetes, epilepsy, asthma and hypertension)</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Prior randomisation in this study during the current pregnancy</div>\n
      • primary_end_points<div>\n PCR-adjusted adequate clinical and parasitological response (ACPR) by Day 42</div>\n<div>\n A composite endpoint of miscarriage, stillbirth, or major congenital anomalies. </div>\n<div>\n  </div>\n
      • scope_diagnosis0
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      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n <u><strong>Chief Investigator</strong></u></div>\n<div>\n Prof Feiko ter Kuile, MD, PhD, Professor of Tropical Epidemiology, Department of Clinical Sciences, Liverpool School of Tropical Medicine (LSTM), Pembroke Place, L3 5QA Liverpool, United Kingdom Tel +44 151 705 3287; and KEMRI-CGHR, P.O. Box 1578, Kisumu 40100, Phone: +254 708 739 228, Email:  feiko.terkuile@lstmed.ac.uk</div>\n<div>\n <u><strong>Principal Investigator</strong></u></div>\n<div>\n Dr Hellen Barsosio, MD, Clinical Epidemiologist, KEMRI Centre for Global Health Research (CGHR), P.O. Box 1578, Kisumu 40100, Kenya, Phone: +254 719 436 833, Email: hellen.barsosio@lstmed.ac.uk  </div>\n<div>\n <u><strong>Co-Investigator</strong></u></div>\n<div>\n •<span style=\"white-space:pre\"> </span>Sally Wambui Ndungu, MD, trial manager, Sally.Wambui@ke.lstmed.ac.uk</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Simon Kariuki, PhD, Head Malaria Division, skariuki1578@gmail.com,  skkariuki@kemri.go.ke </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Evelyn Delylah Ondieki, MPH, study coordinator, evelyne.delylah@lstmed.ac.uk </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Kephas Otieno, MSc, head malaria laboratory, kotieno@kemri.org, koti72@gmail.com </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Miriam Chombe, MSc, laboratory scientist, mchomba@kemri.go.ke </div>\n<div>\n •<span style=\"white-space:pre\"> </span>Benard Omondi, PharmD, Pharmaco-epidemiologist, benard.omondi@ke.lstmed.ac.uk</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Patricia Odera-Ojwang , MD, Consultant paediatrician, pattojey@gmail.com</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Jonathan Schultz, MD, Infectious Disease specialist, rix1@cdc.gov</div>\n<div>\n •<span style=\"white-space:pre\"> </span>Bixa Ogola, PhD, laboratory scientist, bixa.ogola@gmail.com</div>\n<div>\n  </div>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration28 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorArtemether-Lumefantrine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaThe Kenya Medical Research Institute (KEMRI), Centre for Global Health Research (CGHR)
      • single_site_physical_addressP.O. Box 1578-40100, Kisumu, Kenya.
      • single_site_contact_personDr. Hellen Barsosio
      • single_site_telephone+254719436833
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesThree
      • number_of_sites
      • multi_country_listKenya\nMali\nBurkina Faso
      • data_monitoring_committeeYes
      • total_enrolment_per_site504
      • total_participants_worldwide504
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsYes
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      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
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      • subjects_othersNo
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      • investigator1_given_nameFeiko
      • investigator1_middle_name
      • investigator1_family_nameter Kuile
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
      • investigator1_telephone+254708739228
      • investigator1_emailfeiko.terkuile@lstmed.ac.uk
      • organisations_transferred_No
      • number_participants504
      • notification
      • approval_date15-10-2025
      • submitted1
      • deleted0
      • deleted_date(null)
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      • date_submitted30-05-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted30-05-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed
      • final_report(null)
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      • quantity_imported(null)
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      • balance_site(null)
      • final_date(null)
      • modified2025-10-15 18:43:00
      • created2025-05-09 07:50:31
      • total_sites1
      • ecitizen_invoice370504
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        • id1291
        • application_id1540
        • given_nameHellen
        • middle_name
        • family_nameBarsosio
        • qualificationMD, PhD
        • professional_addressKEMRI CGHR 1578-40100 Kisumu, Kenya
        • telephone+254719436833
        • emailhellen.barsosio@lstmed.ac.uk
        • created2025-05-26 11:39:54
        • modified2025-06-10 11:17:45
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        • created2025-05-26 11:39:54
        • modified2025-06-10 11:17:45
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    • Sponsor(array)
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        • id841
        • application_id1540
        • sponsorLiverpool School of Tropical Medicine (LSTM)
        • sponsor_typeResearch Institution
        • contact_personProf Feiko ter Kuile, MD, PhD
        • addressPembroke Place, Liverpool L3 5QA, UK.
        • telephone_number+44 0151 7053794
        • fax_number+44 0151 7053794
        • cell_number+44 0151 7053794
        • email_addresslstmgov@lstmed.ac.uk
        • created2025-05-26 11:39:54
        • modified2025-06-10 11:17:45
  • 1(array)
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      • id1474
      • user_id263
      • trial_status_id1
      • abstract_of_study<div>\n Early and accurate diagnosis of an infectious disease such as HIV, TB and malaria is very important in helping control the burden the such an infectious disease. Early andaccurate diagnosis enables early initiation of treatment before the start of complications.</div>\n<div>\n The current mainstay of diagnosis in all these infectious diseases involve invasive techniques and which do not give real time results. The mainstay of malaria, HIV and TB diagnosis has been blood smear for malaria microscopy, HIV antibody testing and sputum for microscopy (acid fast bacilli) and culture or gene expert respectively. The need for waiting time to get the results makes the diagnostic tests above not very useful for screening, especially in the community.</div>\n<div>\n As a consequence of the unmet need for an ideal screening test for these highly prevalent diseases, EDE research institute is investigating a device, that has a potential to diagnose malaria, TB and HIV in both asymptomatic and symptomatic individuals.</div>\n<div>\n This is a multinational, multicenter, cross-sectional observational study in which approximately 2320 eligible participants, male and female, aged 18 years and above will be recruited in 3 groups. We propose to recruit at about 500 participants, 18 years and above at the ACTU site. The duration of participation for each participant will be approximately 1 day, inclusive of recruitment and follow up of the participants until study conclusion.</div>\n<div>\n All statistical analyses described in the main protocol will be applied based on the same methodology independently, unless otherwise specified.</div>\n<div>\n The publication of the results of the trial will be done in peer reviewed scientific journals in accordance with the governing clinical trial agreement, presented at scientific conferences and findings communicated to the local community through the Community Health Volunteers, Ministries of Health. Individual participants may also be reached and provided with the information if they wish to receive it individually.</div>\n<div>\n The data obtained in this study will be used to validate the EDE scanner for the diagnosis of malaria, tuberculosis and HIV.</div>\n
      • study_title<p>\n A non-interventional clinical validation study of the Exponential Deep Examination (EDE) scanner in the detection of human immunodeficiency virus (HIV), tuberculosis (TB) and malaria</p>\n
      • laymans_summary<div>\n Exponential Deep Examination (EDE) scanner is an innovative device designed to detect infectious diseases and antimicrobial resistance, developed by the parent company of Servizi EDE Research LLC, which has been carrying out research and scouting technology for more than 10 years, developing, among the others, a technology for noninvasive genome detection. Such technology can detect electromagnetic (EM) waves from individuals within a 2–5 meter radius. As EM waves differ among healthy (noninfected) versus infected individuals due to presence of pathogenic DNA/RNA sequences, the technology classifies these EM waves based on their spectral signatures and subsequently identifies the pathogen based on its corresponding sequence.</div>\n<div>\n The technology researched and fine-tuned by the parent company of Servizi EDE Research LLC comprises three main elements:</div>\n<div>\n (1) An EDE detector (sensor) to measure EM waves;</div>\n<div>\n (2) A portable targeting device: Android based device (smartphone) connected to the internet to transmit information and point to a certain individual and display</div>\n<div>\n information; and</div>\n<div>\n (3) A machine learning (ML) model to identify the spectral signature compatible with the specific pathogen.</div>\n<div>\n The same technology was used by the parent company of Servizi EDE Research LLC as a component to develop and fine-tune another type of scanner, which demonstrated high accuracy in detecting the Coronavirus Disease 2019 (COVID-19) (i.e., the COVID-19 EDE scanner). When tested in the Emirate of Abu Dhabi in the United Arab Emirates (UAE), the COVID-19 EDE scanner showed device sensitivity and specificity of 96.7% and 98.12%, respectively, against the gold standard COVID-19 polymerase chain reaction (PCR) test. Moreover, similar results were shown in a study conducted by the Abu Dhabi Health Services Company (SEHA) and Union 71 laboratory testing firm, whereby analysis of 1,093 patient samples yielded a sensitivity and specificity of 93.5% and 83.0%, respectively, in the detection of COVID-19 using the COVID-19 EDE scanner.</div>\n<div>\n Based on these data, the Health Department of Abu Dhabi approved the use of COVID-19 EDE scanner as a screening technology in the detection of COVID-19, whereby individuals screened positive for COVID-19 via the scanner would subsequently undergo RT-PCR testing to confirm the diagnosis of COVID-19. The COVID-19 EDE Scanner was widely used as a mandatory screening tool to detect COVID-19 at land/air entry points, shopping malls and residential areas in Abu Dhabi during the COVID-19 pandemic.</div>\n<div>\n The EDE scanner has the potential to detect other pathogens as well, including human immunodeficiency virus (HIV), tuberculosis (TB), and hepatitis C (HCV), as</div>\n<div>\n demonstrated through a preliminary study by Servizi EDE Research LLC (100% sensitivity and specificity in detection of HIV, TB, and HCV). This preliminary study was conducted among 74 patients from hospitals across the UAE that included patients suspected of HIV as well as confirmed cases of HCV and TB. The EDE scanner successfully detected all the suspected and symptomatic patients with HIV, HCV, and TB, as confirmed against the standard diagnostic tests performed for each of these infections (HIV: HIV viral load and HIV antibody test; HCV: anti-HCV antibody test and nucleic acid test; TB: acid fast bacilli test). Furthermore, EDE scanner may be used to detect antimicrobial resistance. Thus, with prospects to detect a wide range of pathogens and antimicrobial resistance, the EDE scanner has the potential to be used in various settings, including visa screening centers, hospitals, clinics, laboratories, airports, malls, land/air entry points, as well as for other commercial purposes.</div>\n<div>\n Unique features of the EDE scanner include its ability to generate results in real-time (immediately), and its non-invasiveness (no direct contact is required). The device can be used as a screening tool to prompt further diagnostic testing. Such novel diagnostic screening technology is even more important in countries with limited resources and limited access to conventional diagnostic laboratory infrastructure. These technological advancements may reduce the existing gap between diagnostic needs and diagnostic access especially in the middle- and low- income countries (such as African countries), where despite the substantial burden of infectious diseases, only 19% of patients have access to appropriate diagnostics at the primary health care level.</div>\n<div>\n The African continent bears the largest burden of infectious diseases worldwide. Of the estimated 10 million deaths globally per year caused by infectious diseases, the majority occur in Africa. Key contributors to this excessive burden include widespread HIV, malaria, and TB infections, which together account for nearly over 1.2 million deaths per year on the continent. Within the continent, HIV and malaria are highly prevalent across South Africa and Kenya, which are also among the 30 countries worldwide with high burden of TB and MDR-TB.</div>\n
      • short_titleEDE Scanner Study
      • protocol_noECCT/24/10/03
      • version_no1.1
      • date_of_protocol17-07-2024
      • study_drugN/A
      • disease_conditionMalaria, Tuberculosis, HIV and Hepatitis C virus
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameEDE scanner
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data1
      • applicant_stability_data0
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan0
      • applicant_contractual_agreement1
      • declaration_applicantElizabeth Miron
      • declaration_date114-10-2024
      • declaration_principal_investigatorBernhards Ogutu- NPI
      • declaration_date214-10-2024
      • placebo_presentNo
      • study_objectives<div>\n <strong>Primary objective</strong></div>\n<div>\n To assess the sensitivity, specificity, PPV, and NPV of EDE scanner in the detection of infectious diseases of interest (HIV, TB,</div>\n<div>\n malaria)</div>\n<div>\n  </div>\n<div>\n <strong>Secondary objective</strong></div>\n<div>\n To determine the frequency of symptoms (at enrollment) among patients screened positive and screened negative via EDE</div>\n<div>\n scanner, for each infectious disease of interest (HIV, TB, malaria), among patients with confirmed disease*</div>\n<div>\n  </div>\n<div>\n <strong>Exploratory objectives</strong></div>\n<div>\n To assess the sensitivity, specificity, PPV, and NPV of EDE scanner in the detection of MDR-TB.</div>\n<div>\n To assess the sensitivity, specificity, PPV, and NPV of EDE scanner in the detection of HCV.</div>\n
      • principal_inclusion_criteria<div>\n <strong>Inclusion criteria</strong></div>\n<div>\n <strong>For Group 1 (symptomatic patients suspected of HIV/TB/malaria/HCV):</strong></div>\n<div>\n • Male or female, aged ≥18 years</div>\n<div>\n • Asymptomatic/symptomatic patients suspected of HIV, or symptomatic patients suspected of TB, malaria, or HCV based on</div>\n<div>\n physician’s clinical evaluation, which may include laboratory (eg, liver function tests, CBC) or radiological (eg, chest X-ray)</div>\n<div>\n tests per routine clinical practice</div>\n<div>\n • Patient agrees to undergo the non-invasive EDE scanner test and standard diagnostic testing for the respective infectious</div>\n<div>\n disease (HIV/TB/malaria/HCV) - per routine standard of care, in parallel</div>\n<div>\n • Provision of signed informed consent For Group 2 (healthy participants):</div>\n<div>\n • Male or female, aged ≥18 years</div>\n<div>\n • Healthy participant, as determined by physician’s judgment</div>\n<div>\n • Participant undergoing routine blood test as per standard of care</div>\n<div>\n • Participant agrees to undergo non-invasive EDE scanner test</div>\n<div>\n • Participant permits use of the routine blood sample to conduct a standard diagnostic test for HIV, malaria, or HCV; or,</div>\n<div>\n participant agrees to provide a sputum sample to conduct a standard diagnostic test for TB</div>\n<div>\n • No evidence of active infectious disease or any infectious disease in the past 8 weeks</div>\n<div>\n • No history of any of the following in the past 6 months (at minimum): close contact with infected patients or infectious</div>\n<div>\n disease department, open/unprotected relations, drug abuse, blood transfusions</div>\n<div>\n • Provision of signed informed consent</div>\n<div>\n For Group 3 (suspected MDR-TB patients):</div>\n<div>\n • Male or female, aged ≥18 years</div>\n<div>\n • Patients with documented pulmonary TB due to strains of Mycobacterium tuberculosis, currently on TB treatment as per</div>\n<div>\n routine clinical practice and suspected of MDR-TB based on physician’s clinical evaluation (eg, lack of treatment response to</div>\n<div>\n both isoniazid and rifampicin)</div>\n<div>\n • Patient agrees to undergo the non-invasive EDE scanner test and standard diagnostic testing for MDR TB (per routine</div>\n<div>\n standard of care), in parallel</div>\n<div>\n • Provision of signed informed consent</div>\n<div>\n <table align=\"left\" cellpadding=\"0\" cellspacing=\"0\" hspace=\"0\" vspace=\"0\">\n <tbody>\n <tr>\n <td align=\"left\">\n <p>\n <u>For Group 2 (healthy participants):</u></p>\n <p style=\"margin-left:.5in;\">\n ·       Male or female, aged ≥18 years</p>\n <p style=\"margin-left:.5in;\">\n ·       Healthy participant, as determined by physician’s judgment</p>\n <p style=\"margin-left:.5in;\">\n ·       Participant undergoing routine blood test as per standard of care</p>\n <p>\n ·       Participant agrees to undergo non-invasive EDE scanner test</p>\n <p>\n ·       Participant permits use of the routine blood sample to conduct a standard diagnostic test for HIV, malaria, or HCV; or, participant agrees to provide a sputum sample to conduct a standard diagnostic test for TB</p>\n <p style=\"margin-left:.5in;\">\n ·       No evidence of active infectious disease or any infectious disease in the past 8 weeks</p>\n <p style=\"margin-left:.5in;\">\n ·       No history of any of the following in the past 6 months (at minimum): close contact with infected patients or infectious disease department, open/unprotected relations, drug abuse, blood transfusions</p>\n </td>\n </tr>\n </tbody>\n </table>\n <div style=\"clear:both;\">\n Provision of signed informed consent</div>\n</div>\n<table align=\"left\" cellpadding=\"0\" cellspacing=\"0\" hspace=\"0\" vspace=\"0\">\n <tbody>\n <tr>\n <td align=\"left\">\n <p>\n <u>For Group 3 (suspected MDR-TB patients):</u></p>\n <ul>\n <li>\n Male or female, aged ≥18 years</li>\n <li>\n Patients with documented pulmonary TB due to strains of <em>Mycobacterium tuberculosis, </em>currently on TB treatment as per routine clinical practice and suspected of MDR-TB based on physician’s clinical evaluation (eg, lack of treatment response to both isoniazid and rifampicin)</li>\n <li>\n Patient agrees to undergo the non-invasive EDE scanner test and standard diagnostic testing for MDR-TB (per routine standard of care), in parallel</li>\n <li>\n Provision of signed informed consent</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<div style=\"clear:both;\">\n  </div>\n
      • principal_exclusion_criteria<table align=\"left\" cellpadding=\"0\" cellspacing=\"0\" hspace=\"0\" vspace=\"0\">\n <tbody>\n <tr>\n <td align=\"left\">\n <p>\n <strong><em>Exclusion criteria</em></strong></p>\n <p>\n <u>For Group 1 (symptomatic patients suspected of HIV/TB/malaria/HCV):</u></p>\n <ul>\n <li>\n Current or previous history of treatment for HIV, TB, malaria, or HCV</li>\n </ul>\n <p style=\"margin-left:.5in;\">\n ·       Patients suspected to be co-infected with more than one of the infectious diseases of interest (HIV/TB/malaria/HCV)</p>\n <ul>\n <li>\n Current or previous participation in any investigational drug or medical device study in the past 3 months</li>\n <li>\n Patients on any concomitant antibiotic or antiviral treatment</li>\n </ul>\n <p>\n <u>For Group 2 (healthy participants):</u></p>\n <ul>\n <li>\n Current or previous participation in any investigational drug or medical device study in the past 3 months</li>\n <li>\n Participants on any concomitant antibiotic or antiviral treatment</li>\n </ul>\n <p>\n <u>For Group 3 (suspected MDR-TB patients):</u></p>\n <ul>\n <li>\n Previous history of treatment for MDR-TB or extensive drug resistance TB (XDR-TB)</li>\n <li>\n Current or previous participation in any investigational drug or medical device study in the past 3 months</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\n<div style=\"clear:both;\">\n  </div>\n<p>\n Patients on any concomitant antibiotic or antiviral treatment</p>\n
      • primary_end_points<div>\n Sensitivity, specificity (with 95% CI), PPV, and NPV of EDE scanner compared with reference standard diagnostic tests in the detection of infectious diseases of interest (HIV, TB, malaria).</div>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyObservational Study
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<div>\n  </div>\n<div>\n <strong>Site Siaya Clinical Trials Annex</strong></div>\n<div>\n 1. PI Prof. Videlis Nduba</div>\n<div>\n 2. Sub-Investigators</div>\n<div>\n Dr Mercy Muderi Mwale - Medical Officer</div>\n<div>\n Dr. Mike Odoyo: Medical Officer</div>\n<div>\n 3. Pharmacists</div>\n<div>\n Dr. Ian Mwangi</div>\n<div>\n Emily Naiserian</div>\n<div>\n  </div>\n<div>\n <strong>Ahero Clinical Trials Unit</strong></div>\n<div>\n 1. PI Dr Bernhards Nduba</div>\n<div>\n 2. Sub-Investigators.</div>\n<div>\n Dr. John Orimbo</div>\n<div>\n Dr. Fredrick Olewe</div>\n<div>\n Dr. Godfrey Allan Otieno</div>\n<div>\n Dr. John Michael Ong’echa</div>\n<div>\n 3. Pharmacists</div>\n<div>\n Dr. Ruth Wasuna</div>\n<div>\n Dr. Simeon Onyango</div>\n<div>\n  </div>\n<div>\n <div>\n <strong>VIBRI Site</strong></div>\n <div>\n <br />\n <div>\n 1. PI Dr. Lucas Otieno Tina, MBChB MSc. DLSHTM</div>\n <div>\n 2. Sub-Investigators- Dr. Walter Otieno, MBChB, MMED (Paeds), PhD</div>\n <div>\n Dr. Antony Oindo, MBChB</div>\n <div>\n Dr. Kenson Nyolmo Kipchumba, MBChB</div>\n <div>\n Dr. Diana Odhiambo, MBChB, MBA, MPH</div>\n <div>\n Dr. Grace Lanoi, MBChB, MMED (Paeds)</div>\n 3. Pharmacist: Dr. Melanie Miruka, BPharmI Dr. Lucas Otieno Tina, MBChB MSc. DLSHTM</div>\n <div>\n 2. Sub-Investigators- Dr. Walter Otieno, MBChB, MMED (Paeds), PhD</div>\n <div>\n Dr. Antony Oindo, MBChB</div>\n <div>\n Dr. Kenson Nyolmo Kipchumba, MBChB</div>\n <div>\n Dr. Diana Odhiambo, MBChB, MBA, MPH</div>\n <div>\n Dr. Grace Lanoi, MBChB, MMED (Paeds)</div>\n <div>\n 3. Pharmacist: Dr. Melanie Miruka, BPharm</div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<div>\n The Study Primary Objective is to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EDE scanner in the detection of infectious Sensitivity, specificity (with 95% CI), PPV, and NPV of EDE scanner compared with reference standard diseases of interest (HIV, TB, malaria).</div>\n<div>\n The African continent bears the largest burden of infectious diseases worldwide. Of the estimated 10 million deaths globally per year caused by infectious diseases, the majority occur in Africa. Key contributors to this excessive burden include widespread HIV, malaria, and TB infections, which together account for nearly over 1.2 million deaths per year on the continent. Within the continent, HIV and malaria are highly prevalent across South Africa and Kenya, which are also among the 30 countries worldwide with high burden of TB and MDR-TB.</div>\n<div>\n There is no pool of patients in the host country UAE for HIV, Malaria and TB.</div>\n<div>\n A previous study on this device was done in UAE on COVID 19. Protocol Synopsis of this study (protocol EDECOVID02) is included in this application. The study was designed for 5-7 sites and 1500 participants from UAE.</div>\n<div>\n Sponsor also investigated the epidemiological status of tuberculosis (TB), hepatitis C(HCV), and human immunodeficiency virus (HIV), in different hospitals inUAE.</div>\n<div>\n The EDE machine was tested on:</div>\n<div>\n • 14 people who were quarantined in the hospitals and suspected of having HIV.</div>\n<div>\n • 51 cases of Hepatitis C</div>\n<div>\n • 9 cases of TB infection</div>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n South Africa Health Product Regulatory Authority, approval was granted on 12 Aug 2024 for 2 sites in South Africa</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration6-8 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites3
      • multi_country_listKenya and South Africa
      • data_monitoring_committeeNo
      • total_enrolment_per_siteA proximately 387 participants will be enrolled per site
      • total_participants_worldwide2320
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationYes
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMBChB MPH
      • investigator1_professional_addressP.O BOX 54-40100 KISUMU
      • investigator1_telephone0733812613
      • investigator1_emailOgutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants1160
      • notification
      • approval_date07-04-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-10-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted14-10-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-11-10 13:20:30
      • created2024-10-08 10:21:23
      • total_sites2
      • ecitizen_invoice322203
    • InvestigatorContact(array)
      • 0(array)
        • id1171
        • application_id1474
        • given_nameVIDELIS
        • middle_name
        • family_nameNduba
        • qualificationMBChB MPH PHD
        • professional_addressP.O BOX 254 NAIROBI
        • telephone0724522474
        • emailvnduba@kemri.go.ke
        • created2024-10-08 10:23:23
        • modified2024-11-14 15:54:49
      • 1(array)
        • id1172
        • application_id1474
        • given_nameBerngards
        • middle_name
        • family_nameOgutu
        • qualificationMBChB MPH
        • professional_addressP.O BOX 54-40100 KISUMU
        • telephone0733812613
        • emailOgutu6@gmail.com
        • created2024-10-08 11:11:02
        • modified2024-11-14 15:54:49
    • SiteDetail(array)
      • 0(array)
        • id1792
        • application_id1474
        • county_id42
        • site_nameAhero Clinical Trials Unit
        • physical_addressAhero clinical trial Unit insite ahero Sub-County Hospital along Kisumu Nairobi highway
        • contact_details0733812613
        • contact_personDr Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2024-10-08 10:23:23
        • modified2024-11-14 15:54:49
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1793
        • application_id1474
        • county_id41
        • site_nameKEMRI/CRDR Siaya Clinical trials Annex
        • physical_addressSiaya Clinical trials annex Insite Siaya Country referral Hospital
        • contact_details0724522474
        • contact_personProf Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2024-10-08 11:36:30
        • modified2024-11-14 15:54:49
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 2(array)
        • id1794
        • application_id1474
        • county_id42
        • site_nameVICTORIA BIOMEDICAL RESEARCH INSTITUTE
        • physical_addressKisumu County Referral Hospital
        • contact_detailsP.O Box 2109, Kisumu, Kenya, Postal Code 40100
        • contact_personLucas Tina
        • site_capacity(null)
        • misc(null)
        • created2024-10-08 11:36:30
        • modified2024-11-14 15:54:49
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id785
        • application_id1474
        • sponsorServizi EDE Research LLC,
        • sponsor_typeIndustry
        • contact_personSalvatore Spagna
        • addressSharjah Media City, Sharjah, United Arab Emirates
        • telephone_number+971562240274
        • fax_number
        • cell_number+971562240274
        • email_addresssalvo.spagna@ede.ae
        • created2024-10-08 10:23:23
        • modified2024-11-14 15:54:49
  • 2(array)
    • Application(array)
      • id431
      • user_id302
      • trial_status_id(null)
      • abstract_of_study<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 100%;\" width=\"100%\">\n <tbody>\n <tr>\n <td style=\"width: 23.8%;\">\n <p align=\"left\">\n <strong>Data analysis</strong></p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p align=\"center\">\n  </p>\n </td>\n <td style=\"width: 76.2%;\">\n <p>\n Data Analysis: PK parameters:</p>\n <p>\n The disposition of Captopril following oral administration will be characterized according to the following equation for a one compartment model with an absorption phase and an elimination phase: C_p = (F.D/V)[Ka/(Ka-K)[ {exp[-K(t-t_lag)], where F is the fraction of administered dose which is bioavailable, D is the administered dose, V is the apparent volume of distribution, and the other terms are as defined above . The PK data fitting program Phoenix WinNonlin (Version 6.2 or higher), or a suitable alternative, will be used to fit the data according to this equation.</p>\n <p>\n The following PK parameters will be calculated:</p>\n <ul>\n <li>\n AUC_last will be calculated using the linear  trapezoidal rule</li>\n <li>\n AUC_inf will be estimated as the sum of AUC_last and the terminal area determined from C_last/T_last.</li>\n <li>\n C_max, and T_max, will be observed maximum drug concentration and the corresponding times, respectively</li>\n <li>\n T1/2 will be estimated from the terminal elimination phase drug concentration-time date using standard PK procedures. Data will be summarized as mean [95% confidence interval) except for age, C_max and T_max, which will be expressed as median (range).</li>\n </ul>\n <p>\n Safety parameters:</p>\n <p>\n Descriptive statistics of subjects’ safety data will be carried out. The number and percentage of subjects with adverse events will be tabulated by system organ class and preferred term.</p>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • study_title<p>\n A non-randomized, open label, single dose, pharmacokinetics, safety and tolerability study of Captopril 50mgs in healthy Kenyan Adults.</p>\n
      • laymans_summary(null)
      • short_title(null)
      • protocol_noECCT/15/10/02
      • version_noV3
      • date_of_protocol17-08-2015
      • study_drugCaptopril
      • disease_conditionHypertension
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_namecaptopril
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressbernhards.ogutu@usamru-k.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr. Bernhards Ogutu
      • declaration_date114-10-2015
      • declaration_principal_investigatorDr. Bernahrds Ogutu
      • declaration_date214-10-2015
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<ul>\n <li>\n Obtained written informed consent.</li>\n <li>\n Adult male and female(non-child bearing potential) subjects 18 to 45 years of age old, weighing at least 50 kg ,  with  a body mass index (BMI) within the range of 18-30 kg/m² and in good health as determined by past medical history, physical examination, vital signs, and laboratory tests at screening, will be included.</li>\n</ul>\n<ul>\n <li>\n Able to communicate well with the investigator and to understand and comply with the requirements of the study.</li>\n <li>\n Minimum of Four education qualification</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Use of Captopril or any other ACE inhibitor at the time of enrollment, or within 5 half-lives of enrollment.</li>\n <li>\n Known history of hypersensitivity to Captopril or (ACE) inhibitors.</li>\n <li>\n Known medical history of hereditary/idiopathic angioneurotic edema.</li>\n <li>\n History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.</li>\n</ul>\n<ul>\n <li>\n Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation. Pregnancy is confirmed by a positive pregnancy test.</li>\n <li>\n Donation or loss of 450 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation.</li>\n <li>\n Significant illness which has not resolved within two (2) weeks prior to initial dosing.</li>\n <li>\n Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.</li>\n <li>\n History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and/or baseline.</li>\n <li>\n Refusal to give Informed Consent.</li>\n</ul>\n
      • primary_end_points<p>\n The following PK parameters will be calculated:</p>\n<ul>\n <li>\n AUC_last will be calculated using the linear  trapezoidal rule</li>\n <li>\n AUC_inf will be estimated as the sum of AUC_last and the terminal area determined from C_last/T_last.</li>\n <li>\n C_max, and T_max, will be observed maximum drug concentration and the corresponding times, respectively</li>\n <li>\n T1/2 will be estimated from the terminal elimination phase drug concentration-time date using standard PK procedures. Data will be summarized as mean [95% confidence interval) except for age, C_max and T_max, which will be expressed as median (range).</li>\n</ul>\n<p>\n Safety parameters:</p>\n<p>\n Descriptive statistics of subjects’ safety data will be carried out. The number and percentage of subjects with adverse events will be tabulated by system organ class and preferred term.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n  The centre has a 28 bed ward capacity with clinical laboratory for safety evelautaion, pharmacy for clinical trials, emergency room, patient examination rooms, radiology unit, archives, kitchen, laundry, data management room, offices.</p>\n<p>\n Key staff for the study</p>\n<p>\n 1. Dr. Bernhards Ogutu, MMed (paeds), PhD (clinical pharmacology)  - 20 years clinical trials experience</p>\n<p>\n 2. Dr. Elizabeth Juma, MMed (obs/gyn), MPH, 10 years clinical trials experience</p>\n<p>\n 4. Dr. Kevin Omondi , MBChB, - Years clinical trials Experience</p>\n<p>\n 5. Dr. Andrew Omandi Cole MBChB, - 3 years clinical trials experience</p>\n<p>\n 5. Ms. Charity Maingi, KRN, Msc, clinical research coordinator, 8 years clinical trials experience</p>\n<p>\n  </p>\n<p>\n 12 lab techs and 16 nurses who have GCP training. </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n Pharmacy and Poisons Board, Kenya</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration1 year
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI centre for clinical Research
      • single_site_physical_addressMbagathi way, P.O.Box 54840 -0200 Nairobi
      • single_site_contact_personBernhards Ogutu
      • single_site_telephone0733812613
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site20
      • total_participants_worldwide20
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_nameRagama
      • investigator1_family_nameOgutu
      • investigator1_qualificationMBChB, MMed, PhD
      • investigator1_professional_addressP.O.Box 2254 Nairobi
      • investigator1_telephone0733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_No
      • number_participants20
      • notification
      • approval_date02-12-2015
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted21-10-2015
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2015-12-02 12:36:31
      • created2015-10-14 16:21:15
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id289
        • application_id431
        • given_nameBernhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMBChB, MMed, Phd
        • professional_addressP.O.Box 2254 Nairobi
        • telephone0733812613
        • emailogutu@gmail.com
        • created2015-10-14 16:57:33
        • modified2015-10-21 11:46:35
    • SiteDetail(array)
      • 0(array)
        • id345
        • application_id431
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2015-10-14 16:57:33
        • modified2015-10-21 11:46:35
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id226
        • application_id431
        • sponsorPI
        • sponsor_type(null)
        • contact_person
        • addressP.O.Box 2254
        • telephone_number0733812613
        • fax_number
        • cell_number0733812613
        • email_addressogutu6@gmail.com
        • created2015-10-14 16:57:33
        • modified2015-10-21 11:46:35
  • 3(array)
    • Application(array)
      • id989
      • user_id667
      • trial_status_id8
      • abstract_of_study<p>\n Young women in sub-Saharan Africa are a vulnerable population in terms of HIV acquisition with ~7,000 new infections occurring per week. Oral daily pre-exposure prophylaxis (PrEP) is a highly effective means of HIV prevention when taken regularly. Early experience with the global rollout of PrEP in this population indicates enthusiasm for PrEP, but also barriers to adherence and program retention. PrEP My Way is a novel PrEP delivery system consisting of clinic-based PrEP initiation, followed by peer-delivered kits for HIV self-testing, PrEP refills, vaginal swabs for gonorrhea and chlamydia self-sampling, pregnancy tests, and contraception refills, if desired. Based on Social Cognitive Theory, our overall hypothesis is that PrEP My Way will overcome critical stigma and structural barriers that currently limit PrEP use and thus empower young women to promote their sexual health.</p>\n
      • study_title<p>\n A Novel PrEP Delivery System to Meet the Needs of Young African Women</p>\n
      • laymans_summary<p>\n Young women (defined here as 16-24 years old) in sub-Saharan Africa are a vulnerable population in terms of HIV acquisition with ~7,000 new infections occurring per week. Oral daily pre-exposure prophylaxis (PrEP) is a highly effective means of HIV prevention when taken regularly. Early experience with the global rollout of PrEP in this population indicates enthusiasm for PrEP, but also barriers to adherence and program retention. PrEP My Way is a novel PrEP delivery system consisting of clinic-based PrEP initiation, followed by peer-delivered kits for HIV self-testing, PrEP refills, vaginal swabs for gonorrhea and chlamydia self-sampling, pregnancy tests, and contraception refills, if desired. Based on Social Cognitive Theory, our overall hypothesis is that PrEP My Way will overcome critical stigma and structural barriers that currently limit PrEP use and thus empower young women to promote their sexual health. We will first develop, tailor, and refine PrEP My Way for use with young women in Kisumu, Kenya where we will use a client-centered, iterative approach, involving individual interviews and focus group discussions to optimally design the PrEP My Way kit and peer delivery system. We will then test the intervention for feasibility, acceptability, and preliminary impact on PrEP adherence and program retention. We will randomize 100 Kenyan women to PrEP My Way versus standard of care (i.e., clinic-based delivery of PrEP and sexual health services) and follow them for 6 months. Feasibility will be assessed by receipt of the kit at 1, 3, and 6 months and ability to use its components per protocol. Acceptability will be determined through a mixed-methods interview at 6 months. Preliminary impact will be evaluated by dried blood spot tenofovir levels (adherence) and kit use/clinic attendance at 6 months (retention) as primary outcomes. Mediators and moderators of PrEP use (e.g., empowerment and mental health) will be explored through questionnaires at baseline and 6 months.</p>\n
      • short_titlePrEP My Way
      • protocol_noECCT/21/03/03
      • version_noVersion 1.0
      • date_of_protocol29-10-2019
      • study_drugEmtricitabine/ Tenofovir Disoproxil Fumarate tablets
      • disease_conditionHIV
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameTruvada
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressebukusi@kemri.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantP.O Box 614, 40100
      • declaration_date117-03-2021
      • declaration_principal_investigatorNational Principal Investigator
      • declaration_date217-03-2021
      • placebo_presentNo
      • study_objectives<p>\n 1. Develop PrEP My Way. Using a client-centered approach, we will iteratively conduct individual interviews and focus group discussions with up to 25 Kenyan women (age 16-24) to optimally design PrEP My Way (the kit with instructional materials) and peer delivery system (including phone communication and kit delivery plans).</p>\n<p>\n 2. Assess PrEP My Way for feasibility, acceptability, and preliminary impact on PrEP adherence and program retention. We will randomize 100 Kenyan women (age 16-24) to PrEP My Way versus standard of care (i.e., clinic-based delivery of PrEP and sexual health services) and follow them for 6 months. Feasibility will be assessed by receipt of the kit at 1, 3, and 6 months and ability to use its components per protocol. Acceptability will be determined through a mixed-methods interview. Preliminary impact will be evaluated by dried blood spot tenofovir levels (adherence) and kit use/clinic attendance at 6 months (retention). Potential influencing and mediating socio-behavioral factors will be explored with questionnaires at 0 and 6 months.</p>\n
      • principal_inclusion_criteria<p>\n o Young woman (age 16-24 years); we will enroll emancipated minors (e.g., those who have not yet attained the age of legal competency as defined by state law, but who are entitled to treatment as if they had by virtue of assuming adult responsibilities, such as self-support, marriage, or procreation) per Kenyan national guidelines [39]) or 16-17 year-olds with parental consent</p>\n<p>\n o Reported sexual activity within the past 3 months</p>\n<p>\n o Interest in taking PrEP (actual PrEP uptake is not a requirement for Aim 1)</p>\n<p>\n o Residence in the Kisumu region</p>\n<p>\n o Phone ownership o Ability to understand KiSwahili, DhoLuo, and/or English</p>\n
      • principal_exclusion_criteria<p>\n • Exclusion criteria- inability to provide informed consent (e.g., intoxication, mental disability)</p>\n
      • primary_end_points<p>\n Primary outcomes- Preliminary impact on PrEP adherence and program retention at 6 months. PrEP adherence will be assessed primarily by DBS for tenofovir diphosphate (TFV-DP) concentration. The TFV-DP concentration will provide an estimate of doses taken over the prior 3 months (see Table 4; [11, 50]). Retention will be assessed by kit receipt in the intervention arm and clinic attendance per clinic records in the control arm at Month 6. Potential influencing and mediating socio-behavioral factors (Table 2) will be explored</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyImplementation Science
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n PI- 1</p>\n<p>\n Co-ordinator- 1</p>\n<p>\n Research Assistants- 2</p>\n<p>\n Laboratory Technologist-1</p>\n<p>\n Pharmacist-1</p>\n<p>\n Pharmaceutical Technologist-1</p>\n<p>\n Data Lead-1</p>\n
      • other_details_explanation<p>\n The trial will be conducted in Kenya.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Mass General BrigHam IRB</p>\n<p>\n Approved on December 01 2020</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration6 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKisumu
      • single_site_physical_addressOndiek Street
      • single_site_contact_personKevin Oware
      • single_site_telephone254 723873505
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site100
      • total_participants_worldwide100
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameElizabet Ann
      • investigator1_middle_name
      • investigator1_family_nameBukusi
      • investigator1_qualificationMBChB, MMed, MPH, PhD
      • investigator1_professional_addressBox 19464, post code 00202, Nairobi
      • investigator1_telephone254 733617503
      • investigator1_emailebukusi@kemri.prg
      • organisations_transferred_No
      • number_participants100
      • notification<p>\n None</p>\n
      • approval_date06-07-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-05-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2024-07-10 10:19:36
      • created2021-03-17 14:40:13
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id632
        • application_id989
        • given_nameProf. Elizabet Ann
        • middle_name
        • family_nameBukusi
        • qualificationMBChB, MMed, MPH, PhD
        • professional_addressBox 19464, post code 00202, Nairobi
        • telephone254 733617503
        • emailebukusi@kemri.prg
        • created2021-03-17 14:55:49
        • modified2021-05-25 09:21:39
    • SiteDetail(array)
      • 0(array)
        • id874
        • application_id989
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2021-03-17 14:55:49
        • modified2021-05-25 09:21:39
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id487
        • application_id989
        • sponsorMassachusetts General Hospital
        • sponsor_typeResearch Institution
        • contact_personJessica Haberer
        • address55 Fruit St, Boston, MA 02114, United States
        • telephone_number617-726-2000
        • fax_number
        • cell_number617-726-2000
        • email_addressJHABERER@PARTNERS.ORG
        • created2021-03-17 14:55:49
        • modified2021-05-25 09:21:39
  • 4(array)
    • Application(array)
      • id1012
      • user_id60
      • trial_status_id5
      • abstract_of_study<div>\n Background</div>\n<div>\n  </div>\n<div>\n SARS-CoV-2 is a novel coronavirus that emerged in the human population and has led to a pandemic of acute respiratory disease named COVID-19. The burden of SARS-CoV-2 morbidity and mortality has been catastrophic with greater than 2.8 million deaths recorded since first emerging in December 2019 among over 131.9 million confirmed cases (as of 06 April 2021) (2). In many locations, the rapid emergence of COVID-19 has overwhelmed the capacity of health systems to provide care for COVID-19-affected patients, let alone unaffected patients. Interventions to reduce transmission through reduction of population contact (also called social distancing) has had profound economic consequences. Safe and effective vaccines with sufficient supply would be vital to address the significant medical and societal burden caused by the pandemic.</div>\n<div>\n  </div>\n<div>\n The CoV2 preS dTM-AS03 vaccines developed by Sanofi Pasteur utilize a recombinant protein approach in combination with an oil-in-water adjuvant, AS03 provided by GlaxoSmithKline (GSK). The CoV2 preS dTM-AS03 vaccines belong to the pharmacotherapeutic group of “covid19 vaccines”. The vaccines contain recombinant S protein, stabilized to maintain native prefusion trimer configuration as present on the viral envelope. The purpose of the study is to assess the efficacy, safety, and immunogenicity of two CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) in adults 18 years of age and older in a multi-stage approach.</div>\n<div>\n  </div>\n<div>\n Methods</div>\n<div>\n  </div>\n<div>\n This study is designed to maximize representation of the broader population by minimizing exclusionary eligibility criteria and allowing the participation of individuals with a broad range of medical conditions, including controlled HIV infection, Hepatitis B and Hepatitis C, and conditions associated with an increased risk of severe COVID-19. It is also designed to be inclusive of other subpopulations affected by COVID-19, including older adults as well as ethnic and racial minorities.</div>\n<div>\n Participants will be screened for eligibility criteria at the time of inclusion and then randomized to either the investigational vaccine or placebo in a 1:1 ratio in each stage. • Stage 1: eligible participants will be randomized to receive either 2 injections of CoV2 preS dTM-AS03 (D614) vaccine or Placebo 1 (participants who receive the placebo as part of Stage 1) administered 21 days apart • Stage 2: eligible participants will be randomized to receive 2 injections of either CoV2 preS dTM-AS03 (D614 + B.1.351) vaccine or Placebo 2 (participants who receive placebo as part of Stage 2) administered 21 days apart. Randomization will be stratified by age groups (18-59 years of age and 60 years of age and older), baseline SARS-CoV-2 rapid serodiagnostic test positivity, and site. In the event that the enrollment in Stage 1 overlaps with enrollment of Stage 2, participants will continue to be randomly allocated to one of the investigational vaccine groups and their matched placebo group in a 1:1 ratio.</div>\n<div>\n  </div>\n<div>\n Approximately 37 430 participants are planned to be enrolled (8000 per study intervention group in Stage 1 and 10 715 per study intervention group in Stage 2)The duration of the study for each participant will be 365 days post-last injection (ie, approximately 386 days total). The study includes 8 visits at D01, D22, D43, D78, D134, D202, D292, and D387. Participants will be contacted once a week over the entire duration of the study to inquire about the development of symptoms of COVID-19-like-illness and to remind participants to contact study staff if they experience symptoms of COVID-19-like illness. Additional visits and procedures are included for participants with verified COVID-19-like illness.</div>\n<div>\n  </div>\n
      • study_title<p>\n A parallel-group, Phase III, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years of age and older.</p>\n
      • laymans_summary<p>\n This is a Phase 3 study (efficacy study) of two experimental vaccines against SARS-CoV-2. The full names are:</p>\n<p>\n 1. Monovalent: SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614 (CoV2 preS dTMAS03 [D614])</p>\n<p>\n 2. Bivalent: SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351 (CoV2 preS dTM-AS03 [D614 + B.1.351])</p>\n<ul>\n <li>\n This study is also known as “VAT00008” or “CoVPN 3005.”</li>\n <li>\n The study vaccine is developed by Sanofi Pasteur, a company that produces vaccines against other diseases such as diphtheria, tetanus, pertussis, meningitis and influenza.</li>\n <li>\n The vaccine will be manufactured using the same technology as is used to make an influenza vaccine that is licensed in the US for the prevention of influenza in adults, marketed as Flublok®.</li>\n <li>\n The study will enroll about 37,500 participants globally.</li>\n</ul>\n<ul>\n <li>\n The purpose of the study is to learn if:\n <ul>\n <li>\n The study vaccines can prevent symptomatic COVID-19 illness</li>\n <li>\n The vaccines are safe</li>\n <li>\n The vaccines make people too uncomfortable</li>\n <li>\n The study vaccines can prevent infection with SARS-CoV-2</li>\n <li>\n The study vaccines can prevent severe COVID-19 illness and hospitalization.</li>\n </ul>\n </li>\n</ul>\n
      • short_titleVAT00008
      • protocol_noECCT/21/06/02
      • version_no3.0
      • date_of_protocol18-05-2021
      • study_drugSARS-CoV2 prefusion Spike delta TM (CoV2 preS dTM): antigen formulation at 5 µg or15 µg AS03: CoV2 preS dTM-AS03, Squalene-based adjuvant 2.1%
      • disease_conditionCOVID-19
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_name0.9% Normal saline
      • comparator_registeredyes
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressvnduba@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Videlis Nduba
      • declaration_date110-06-2021
      • declaration_principal_investigatorNational Co-ordinating Investigator
      • declaration_date210-06-2021
      • placebo_presentYes
      • study_objectives<div>\n Key Primary objectives</div>\n<div>\n  </div>\n<ul>\n <li>\n Primary Efficacy: To assess, in participants who are SARS-CoV-2 naïve, the clinical efficacy of the CoV2 preS dTMAS03 vaccines for the prevention of symptomatic COVID-19 occurring ≥ 14 days after the second injection.</li>\n</ul>\n<div>\n  </div>\n<ul>\n <li>\n Primary Safety: To assess the safety of the CoV2 preS dTM-AS03 vaccines compared to placebo throughout the study</li>\n</ul>\n<div>\n  </div>\n
      • principal_inclusion_criteria<div>\n Age</div>\n<div>\n I01: Aged 18 years or older on the day of inclusion</div>\n<div>\n Type of participant and disease characteristics</div>\n<div>\n I02: For persons living with HIV, stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3</div>\n<div>\n I03: SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies</div>\n<div>\n I04: Does not intend to receive an authorized/approved COVID-19 vaccine despite encouragement by the Investigator to receive the authorized vaccine available to them at the time of enrollment</div>\n<div>\n Sex, contraceptive/barrier method and pregnancy testing requirements</div>\n<div>\n I05: A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:</div>\n<div>\n • Is of non-childbearing potential. To be considered of non-childbearing potential, a female must be post-menopausal for at</div>\n<div>\n least 1 year or surgically sterile</div>\n<div>\n  </div>\n<div>\n OR</div>\n<div>\n  </div>\n<div>\n Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first study intervention administration until at least 12 weeks after the second study intervention administration.</div>\n<div>\n A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 25 hours before any dose of study intervention.</div>\n<div>\n Informed Consent</div>\n<div>\n I06: Informed consent form has been signed and dated</div>\n<div>\n Other Inclusions</div>\n<div>\n I07: Able to attend all visits and to comply with all study procedures</div>\n<div>\n I08: Covered by health insurance, only if required by local, regional or national regulations</div>\n
      • principal_exclusion_criteria<div>\n Participants are not eligible for the study if any of the following criteria are met:</div>\n<div>\n Medical conditions</div>\n<div>\n E01: Known systemic hypersensitivity to any of the vaccine components, or history of a lifethreatening reaction to a vaccine containing any of the same substances</div>\n<div>\n E02: Dementia or any other cognitive condition at a stage that could interfere with following the study procedures based on Investigator’s judgment</div>\n<div>\n E03: Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator’s judgment</div>\n<div>\n E04: Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator’s judgment</div>\n<div>\n E05: Unstable acute or chronic illness that in the opinion of the Investigator or designee poses additional risk as a result of participation or that could interfere with the study procedures</div>\n<div>\n E06: Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided</div>\n<div>\n Prior/concomitant therapy</div>\n<div>\n E07: Receipt of any vaccine in the 30 days preceding or on the day of the first study vaccination or planned receipt of any vaccine between the first study vaccination and in the 30 days following the second study vaccination except for influenza vaccination, which may be received at any time in relation to study intervention.</div>\n<div>\n E08: Prior administration of a coronavirus vaccine (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], SARS-CoV, Middle East Respiratory Syndrome [MERSCoV])</div>\n<div>\n E09: Receipt of solid-organ or bone marrow transplants in the past 180 days</div>\n<div>\n E10: Receipt of anti-cancer chemotherapy in the last 90 days</div>\n<div>\n Prior/concurrent clinical study experience</div>\n<div>\n E11: Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure</div>\n<div>\n  </div>\n<div>\n <div>\n Other exclusions</div>\n <div>\n E12: Deprived of freedom by an administrative or court order, or in an emergency setting, or</div>\n <div>\n hospitalized involuntarily</div>\n <div>\n E13: Identified as an Investigator or employee of the Investigator or study center with direct</div>\n <div>\n involvement in the proposed study, or identified as an immediate family member (ie,</div>\n <div>\n parent, spouse, natural or adopted child) of the Investigator or employee with direct</div>\n <div>\n involvement in the proposed study</div>\n <div>\n Depending on country regulations and feasibility, if the participant has a primary physician who is not the Investigator, the</div>\n <div>\n site may contact this physician with the participant’s consent to inform him / her of the participant’s participation in the</div>\n <div>\n study. In addition, the site may ask this primary physician to verify exclusion criteria including but not limited to previous</div>\n <div>\n therapies, such as previous vaccines.</div>\n</div>\n<div>\n  </div>\n
      • primary_end_points<div>\n Primary Efficacy Endpoints</div>\n<div>\n  </div>\n<div>\n Occurrences of symptomatic COVID-19</div>\n<div>\n  </div>\n<div>\n Primary Safety Endpoints</div>\n<div>\n  </div>\n<div>\n For participants in the Reactogenicity Subset:</div>\n<div>\n  </div>\n<div>\n • Presence of solicited (pre-listed in the participant’s diary card / electronic diary card [DC/eDC] and [electronic] Case Report Form [CRF]) injection site reactions and systemic reactions occurring up to 7 days after each vaccination</div>\n<div>\n  </div>\n<div>\n • Presence of non-serious unsolicited adverse events (AEs) reported up to 21 days after the last vaccination</div>\n<div>\n  </div>\n<div>\n For all participants in the study:</div>\n<div>\n  </div>\n<div>\n • Presence of unsolicited injection site and systemic AEs reported in the 30 minutes after each vaccination.</div>\n<div>\n  </div>\n<div>\n • Presence of medically-attended adverse events (MAAEs) throughout the study.</div>\n<div>\n  </div>\n<div>\n • Presence of serious adverse events (SAEs) throughout the study</div>\n<div>\n  </div>\n<div>\n • Presence of adverse events of special interest (AESIs) throughout the study</div>\n<div>\n  </div>\n<div>\n • Presence of virologically-confirmed SARS-CoV-2 infections and/or symptomatic COVID-19</div>\n<div>\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunogenicity
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyPhase III Vaccine Study
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n Medical Officers: 4</div>\n<div>\n  </div>\n<div>\n Laboratory Staff: 6</div>\n<div>\n  </div>\n<div>\n Clinical Officers: 5</div>\n<div>\n  </div>\n<div>\n Data Officers: 4</div>\n<div>\n  </div>\n<div>\n Nurses: 6</div>\n<div>\n  </div>\n<div>\n Pharmacists: 3 </div>\n<div>\n  </div>\n<div>\n Pharmaceutical Technologist: 1</div>\n<div>\n  </div>\n<div>\n Study Coordinators: 1 </div>\n<div>\n  </div>\n<div>\n QA staff: 6</div>\n<div>\n  </div>\n<div>\n Community Engagement: 8</div>\n
      • other_details_explanation<p>\n N/A - trial is being conducted in the host country</p>\n
      • other_details_regulatory_notapproved<div>\n Application to the CBER (USA) on 18 May 2021</div>\n<div>\n  </div>\n<div>\n India: HA submission (Central Drugs Standard Control Organization (CDSCO)) = 13-May-21</div>\n<div>\n  </div>\n<div>\n Mexico: HA submission (Comisión Federal para la Protección Contra Riesgos Sanitarios) = 24-May-21</div>\n
      • other_details_regulatory_approved<p>\n N/A - no approvals have been given yet</p>\n
      • other_details_regulatory_rejected<p>\n N/A - no rejections</p>\n
      • other_details_regulatory_halted<p>\n N/A - study has not been halted</p>\n
      • estimated_duration386 days
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparator0.9% Sodium Chloride
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states14
      • number_of_sites10
      • multi_country_listUSA, Honduras, Dominican Rep, Mexico, Colombia, Japan, India, Pakistan, Sri Lanka, Egypt , Uganda, Kenya, Ghana, Nigeria
      • data_monitoring_committeeYes
      • total_enrolment_per_site250
      • total_participants_worldwide37430
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameVidelis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMBChB,MPH,PhD
      • investigator1_professional_addressCentre for Respiratory Diseases Research, Kenya Medical Research Institute, P.O.Box 47855-00100G.P.O., Nairobi.
      • investigator1_telephone+254724522474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants2000\n
      • notification
      • approval_date02-08-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted08-09-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved
      • final_report<div>\n Study title: A parallel-group, Phase 3, multi-stage, modified double-blind, multi-armed study to assess the efficacy, safety, and immunogenicity of two SARS-CoV-2 Adjuvanted Recombinant</div>\n<div>\n <p>\n Protein Vaccines (monovalent and bivalent) for prevention against COVID-19 in adults 18 years</p>\n <p>\n of age and older as a primary series and open-label extension to assess immunogenicity, safety,</p>\n <p>\n efficacy of a monovalent booster dose of SARS-CoV2 Adjuvanted Recombinant Protein Vaccine</p>\n <p>\n Study number: VAT00008</p>\n <p>\n Regulatory agency identifier number(s):</p>\n <p>\n BB-IND: 23143</p>\n <p>\n WHO: U1111-1264-3238</p>\n <p>\n Clinicaltrials.gov: NCT04904549</p>\n <p>\n Study phase: 3</p>\n <p>\n Compounds:</p>\n <p>\n SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent D614</p>\n <p>\n (CoV2 preS dTM-AS03 [D614]): monovalent vaccine with the Spike (S) protein sequence from</p>\n <p>\n the D614 variant</p>\n <p>\n SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, bivalent D614/B.1.351</p>\n <p>\n (CoV2 preS dTM-AS03 [D614 + B.1.351]): bivalent vaccine with the S protein sequence from the</p>\n <p>\n D614 variant and the B.1.351 variant</p>\n <p>\n SARS-CoV2 prefusion Spike delta TM with AS03 adjuvant, monovalent B.1.351</p>\n <p>\n (CoV2 preS dTM-AS03 [B.1.351]): monovalent vaccine with the S protein sequence from the</p>\n <p>\n B.1.351 variant</p>\n <p>\n Name of Sponsor: Sanofi, Inc.</p>\n <p>\n Number of Study Centers and Countries:</p>\n <p>\n This study was conducted at 87 centers that enrolled participants in the following countries:</p>\n <p>\n Blinded Primary Series:</p>\n <p>\n • Stage 1: United States, Honduras, Japan, Colombia, Kenya, India, Ghana, and Nepal</p>\n <p>\n • Stage 2: Colombia, Kenya, Uganda, India, Ghana, Nepal, Ukraine, and Mexico</p>\n <p>\n • Unblinded Crossover / Booster stage: all countries listed in Stage 1 and Stage 2</p>\n <p>\n Publications (if any):</p>\n <p>\n Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 Protein Vaccine (1).</p>\n <p>\n Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03</p>\n <p>\n adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial</p>\n <p>\n (2).</p>\n <p>\n Efficacy of a monovalent (D614) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant</p>\n <p>\n in adults: a phase 3, multi-country study (3).</p>\n <p>\n Study period:</p>\n <p>\n 26 May 2021 (FPFV) to 31 August 2024 (LPLC)</p>\n <p>\n Rationale:</p>\n <p>\n VAT00008 was a Phase 3, randomized, modified double-blind, placebo-controlled, multi-stage,</p>\n <p>\n multi-center, multi-country study to assess the efficacy, safety, and immunogenicity of 2</p>\n <p>\n CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) in adults 18 years of age and older</p>\n <p>\n with 2 stages. In Stage 1, the monovalent vaccine with the prefusion S protein from the prototype</p>\n <p>\n (D614) variant was evaluated against a placebo control. In Stage 2, the bivalent vaccine with the</p>\n <p>\n prefusion S protein from the prototype and South African Beta variants (D614 + B.1.351) was</p>\n <p>\n assessed against a placebo control. Both stages were considered independent to enable generation</p>\n <p>\n of data to support licensure of each candidate vaccine (ie, the monovalent and bivalent vaccine).</p>\n <p>\n The study was designed to demonstrate clinical efficacy of each vaccine (monovalent and</p>\n <p>\n bivalent) in preventing the occurrence of symptomatic COVID-19 with onset at least 14 days after</p>\n <p>\n the 2nd injection in SARS-CoV-2 naïve individuals for Stage 1 and in all individuals regardless of</p>\n <p>\n their prior SARS-CoV-2 infection status for Stage 2. Symptomatic COVID-19 was defined as</p>\n <p>\n having virologically-confirmed SARS-CoV-2 infection with symptoms of a protocol-defined</p>\n <p>\n COVID-19-like illness.</p>\n <p>\n An unblinded crossover / booster phase followed Stage 1 and Stage 2. In the crossover part,</p>\n <p>\n participants in the placebo groups were offered primary vaccination with the monovalent (D614)</p>\n <p>\n vaccine if they did not receive an authorized/approved vaccine series. In the booster part, all</p>\n <p>\n participants received the monovalent (B.1.351) booster vaccine ≥ 4 months post-last dose of the</p>\n <p>\n primary vaccination.</p>\n <p>\n Objectives and endpoints:</p>\n <p>\n The study objectives and the corresponding endpoints for the initial double-blind primary series</p>\n <p>\n and crossover / booster phase are described in the clinical study protocol and presented below</p>\n <p>\n with summary results in “Summary of results and conclusions”.</p>\n <p>\n Methodology:</p>\n <p>\n VAT00008 was a parallel-group, Phase 3, multi-stage, modified double-blind, multi-armed study</p>\n <p>\n to assess the efficacy, safety, and immunogenicity of 2 CoV2 preS dTM-AS03 vaccines</p>\n <p>\n (monovalent and bivalent) as part of primary series vaccinations, as well as a booster injection of</p>\n <p>\n a monovalent CoV2 preS dTM-AS03 vaccine, in adults 18 years of age and older from 16</p>\n <p>\n countries.</p>\n <p>\n At the time of inclusion, participants were screened for SARS-CoV-2 seropositivity status and</p>\n <p>\n stratified according to age.</p>\n <p>\n Blinded primary series: 2 injections of either monovalent (D614) vaccine (Stage 1), bivalent</p>\n <p>\n (D614 + B.1.351) vaccine (Stage 2), or placebo were administered 21 days apart.</p>\n <p>\n Table S1 - Planned sample size and approximate size of subsets in Stage 1</p>\n <p>\n Study Intervention Groups (Stage 1)</p>\n <p>\n Monovalent</p>\n <p>\n (D614)</p>\n <p>\n Placebo</p>\n <p>\n Total Overall 5080 5080</p>\n <p>\n Prior exposure to</p>\n <p>\n SARS-CoV-2</p>\n <p>\n SARS-CoV-2 naïves 3556 3556</p>\n <p>\n SARS-CoV-2 non-naïves Up to 1524 Up to 1524</p>\n <p>\n Reactogenicity Subset ‡ 2000 2000</p>\n <p>\n Random Immunogenicity Subset (RIS)* 1415 559</p>\n <p>\n Non-naive: Capped at approximately 30% of study population in this stage in this stage based on a positive rapid</p>\n <p>\n serodiagnostic test at time of enrolment.</p>\n <p>\n ‡ A subset of participants for which solicited AEs for 7 days after each vaccination and non-serious unsolicited</p>\n <p>\n AEs up to 21 days after the last vaccination were collected.</p>\n <p>\n * RIS is described in detail in Appendix 10.6 of the protocol.</p>\n <p>\n Table S2 - Planned sample size and approximate size of subsets in Stage 2</p>\n <p>\n Study Intervention Groups (Stage 2)</p>\n <p>\n Bivalent</p>\n <p>\n (D614 + B.1.351)</p>\n <p>\n Placebo</p>\n <p>\n Total Overall 5443 5443</p>\n <p>\n Prior exposure to</p>\n <p>\n SARS-CoV-2</p>\n <p>\n SARS-CoV-2 naïves 3810 3810</p>\n <p>\n SARS-CoV-2 non-naïves 1633 1633</p>\n <p>\n Reactogenicity Subset ‡ 2000 2000</p>\n <p>\n Random Immunogenicity Subset (RIS)* 1415 559</p>\n <p>\n ‡ A subset of participants for which solicited AEs for 7 days after each vaccination and non-serious unsolicited</p>\n <p>\n AEs up to 21 days after the last vaccination were collected.</p>\n <p>\n * RIS is described in detail in Appendix 10.6 of the protocol.</p>\n <p>\n Unblinded crossover (placebo recipients in Stage 1 and Stage 2): primary injection(s) of an</p>\n <p>\n authorized/approved vaccine outside of the study (interval of doses dependent on available</p>\n <p>\n vaccine and following local standard of care) or 2 primary series injections administered 21 days</p>\n <p>\n apart of Sanofi’s monovalent (D614) vaccine.</p>\n <p>\n Unblinded booster (placebo and vaccine recipients in Stage 1 and Stage 2): a single injection of</p>\n <p>\n Sanofi’s investigational monovalent (B.1.351) booster vaccine ≥ 4 months post-last dose of the</p>\n <p>\n primary series.</p>\n <p>\n For efficacy, COVID-19-like illness was monitored through active and passive surveillance for</p>\n <p>\n the blinded and unblinded phases.</p>\n <p>\n Number of participants (planned and analyzed):</p>\n <p>\n Blinded primary series: Approximately 21 046 participants were planned to be enrolled (5080 per</p>\n <p>\n study intervention group in Stage 1 and 5443 per study intervention group in Stage 2). Of the</p>\n <p>\n 10 160 planned, 10 139 participants were enrolled and randomized in Stage 1 of the study with</p>\n <p>\n age stratification of 18 to 59 years (9304 participants) and 60 years and older (835 participants).</p>\n <p>\n Of the 10 886 planned, 13 002 participants were enrolled and randomized in Stage 2 of the study,</p>\n <p>\n with age stratification of 18 to 59 years (12 221 participants) and 60 years and older</p>\n <p>\n (781 participants).</p>\n <p>\n Unblinded crossover: A total of 6801 participants were unblinded and enrolled with age</p>\n <p>\n stratification of 18 to 59 years (6594 participants) and 60 years and older (207 participants). Of</p>\n <p>\n these, 6526 (96.0%) received the 1st injection and 6442 (94.7%) received the 2nd vaccination.</p>\n <p>\n Unblinded booster: A total of 14237 participants were unblinded, enrolled, and received the</p>\n <p>\n booster vaccine (13556 aged 18 to 59 years and 681 aged 60 years and older).</p>\n <p>\n Diagnosis and main criteria for inclusion and exclusion:</p>\n <p>\n The study was conducted to demonstrate clinical efficacy of each the monovalent and bivalent</p>\n <p>\n vaccines in SARS-CoV-2 naïve (not previously infected) individuals for Stage 1 and in all (naïve</p>\n <p>\n and non-naïve, ie, previously infected) individuals for Stage 2; therefore, to determine their</p>\n <p>\n serostatus participants were tested by a rapid SARS-CoV-2 serodiagnostic test at the baseline</p>\n <p>\n visit. The study was conducted in adults (males and females) 18 years of age and older. Given the</p>\n <p>\n clinical and epidemiological data from the COVID-19 pandemic that have consistently indicated a</p>\n <p>\n higher risk of severe complications and death in older adults, the study targeted enrollment of</p>\n <p>\n adults aged 60 years of age and older (40% of the study population in each stage). Individuals</p>\n <p>\n with chronic medical conditions were excluded to mitigate the potential (theoretical) risk of</p>\n <p>\n exacerbating the occurrence of critical or fatal outcomes because of study participation. However,</p>\n <p>\n within the age group of 18-59 years, the study targeted inclusion of approximately 35% of</p>\n <p>\n participants with high-risk medical conditions for COVID-19.</p>\n <p>\n The study targeted recruitment of racial and ethnic diversity representative of the countries in</p>\n <p>\n which the study was conducted.</p>\n <p>\n Study interventions, dose, mode of administration, and batch numbers:</p>\n <p>\n A total of 4 different study interventions were administered by intramuscular (IM) route:</p>\n <p>\n 3 CoV2 preS dTM vaccine formulations and a placebo.</p>\n <p>\n Table S3 - Identity of study interventions</p>\n <p>\n Monovalent Vaccine for Primary Series</p>\n <p>\n Intervention Names COVID-19 vaccine (recombinant, adjuvanted) or CoV2 preS</p>\n <p>\n dTM-AS03 (D614)</p>\n <p>\n Use / IMP / Type Experimental / IMP / Vaccine</p>\n <p>\n Dose Form Solution (antigen) and emulsion (AS03 adjuvant) for injection that</p>\n <p>\n once mixed, form a multi-dose vaccine in a vial.</p>\n <p>\n After mixing, the vaccine is a whitish to yellowish homogeneous</p>\n <p>\n milky liquid emulsion.</p>\n <p>\n Dosage Level / Route 0.5 mL per dose / IM injection</p>\n <p>\n Batch Numbers IP0011305, VA024790, VA026441, VA029253, VA032192,</p>\n <p>\n VA033869</p>\n <p>\n Bivalent Vaccine for Primary Series</p>\n <p>\n Intervention Names COVID-19 vaccine (recombinant, adjuvanted) or CoV2 preS</p>\n <p>\n dTM-AS03 (D614 + B.1.351)</p>\n <p>\n Use / IMP / Type Experimental / IMP / Vaccine</p>\n <p>\n Dose Form Solution (antigen) and emulsion (AS03 adjuvant) for injection that</p>\n <p>\n once mixed, form a multi-dose vaccine in a vial.</p>\n <p>\n After mixing, the vaccine is a whitish to yellowish homogeneous</p>\n <p>\n milky liquid emulsion.</p>\n <p>\n Dosage Level / Route 0.5 mL per dose / IM injection</p>\n <p>\n Batch Number VA024901</p>\n <p>\n Placebo</p>\n <p>\n Intervention Names Placebo</p>\n <p>\n Use / IMP / Type Placebo – comparator / IMP / Vaccine</p>\n <p>\n Dose Form Liquid, in a single-vial presentation</p>\n <p>\n Dosage Level / Route 0.5 mL per dose / IM injection</p>\n <p>\n Batch Numbers IP0011304, VA024746, VA025707, VA024894, VA026436</p>\n <p>\n Monovalent Booster Vaccine</p>\n <p>\n Intervention Names Monovalent (B.1.351) CoV2 preS dTM (5 μg antigen) + AS03</p>\n <p>\n (full-dose adjuvant)</p>\n <p>\n Use / IMP / Type Experimental / IMP / Vaccine</p>\n <p>\n Dose Form Solution (antigen) and emulsion (AS03 adjuvant) for injection that</p>\n <p>\n once mixed, form a multi-dose vaccine in a vial.</p>\n <p>\n After mixing, the vaccine is a whitish to yellowish homogeneous</p>\n <p>\n milky liquid emulsion.</p>\n <p>\n Dosage Level / Route 0.5 mL per dose / IM injection</p>\n <p>\n Batch Numbers VA029061, VA031698, VA033206, VA034427</p>\n <p>\n IM: intramuscular; IMP: Investigational Medicinal Product</p>\n <p>\n Duration of study intervention:</p>\n <p>\n The double-blind primary series was planned for 365 days post-second injection (ie,</p>\n <p>\n approximately 386 days total) for each participant.</p>\n <p>\n The unblinded crossover / booster duration was planned as follows:</p>\n <p>\n • For participants who initially received vaccine: 12 months post-booster (ie, approximately</p>\n <p>\n 18 to 24 months)</p>\n <p>\n • For participants who initially received placebo: ≥ 4 months post-last dose of the primary</p>\n <p>\n series + 12 months post-booster (ie, approximately 28 to 34 months)</p>\n <p>\n • For participants who did not consent to continue in the unblinded crossover / booster part</p>\n <p>\n of the study, all study procedures were stopped and participants were discontinued from</p>\n <p>\n the study.</p>\n <p>\n In January 2024, the Sponsor made the decision that for all ongoing COVID-like illness (CLI)</p>\n <p>\n cases, all activities (including phone calls and swabs) were continued per protocol, however, no</p>\n <p>\n new CLIs were collected (or reported as adverse events [AEs]). Therefore, collection of efficacy</p>\n <p>\n and some AE data did not continue through the end of the crossover / booster part as originally</p>\n <p>\n planned. In August 2024, the Sponsor terminated the study early.</p>\n <p>\n Statistical methods:</p>\n <p>\n Stage 1 and Stage 2 participants were to be enrolled and randomized with allocation ratio (1:1)</p>\n <p>\n into vaccine and placebo groups. The power of primary efficacy analysis was driven by the total</p>\n <p>\n number of symptomatic COVID-19 events. The study planned to have 5080 participants in the</p>\n <p>\n vaccine group in Stage 1 to provide at least 92.1% probability to detect an event with 0.05% rate.</p>\n <p>\n In Stage 2, 5443 participants in vaccine group were to provide at least 93.4% probability to detect</p>\n <p>\n an event with 0.05% rate.</p>\n <p>\n Hypothesis testing was only conducted for the primary efficacy objectives. Demonstration of</p>\n <p>\n efficacy included: 1) the LB of CI is > 30%, and 2) the point estimate of VE is > 50%.</p>\n <p>\n Hypothesis testing for key secondary objectives were to be conducted when both of the following</p>\n <p>\n conditions were met:</p>\n <p>\n • The primary objective was demonstrated</p>\n <p>\n • 22 severe COVID-19 cases and 162 infections were collected</p>\n <p>\n The efficacy was considered as demonstrated if the LB of 95% CI (exact method) was greater</p>\n <p>\n than 0%.</p>\n <p>\n Analyses for the other efficacy objectives are descriptive. Analyses of the primary safety</p>\n <p>\n objectives, other secondary objectives, and exploratory objectives are descriptive.</p>\n <p>\n For the primary series, 2 interim analyses were conducted during the trial, one for each study</p>\n <p>\n Stage. For these interim analyses, the study blind was broken at the group level to the Sponsor.</p>\n <p>\n For all details see the Statistical Analysis Plan (SAP).</p>\n <p>\n The analysis presented in this Final CSR was planned to be performed on efficacy,</p>\n <p>\n immunogenicity, and safety data collected up to the end of the unblinded crossover / booster part</p>\n <p>\n of the study. In January 2024, the Sponsor made the decision that for all ongoing COVID-like</p>\n <p>\n illness (CLI) cases, all activities (including phone calls and swabs) were continued per protocol,</p>\n <p>\n however, no new CLIs were collected (or reported as AEs). Therefore, collection of efficacy and</p>\n <p>\n some AE data did not continue through the end of the crossover / booster part as originally</p>\n <p>\n planned.</p>\n <p>\n The focus on this Final CSR is data from the crossover / booster phase of the study while briefly</p>\n <p>\n summarizing the already-reported, blinded primary series data (Stage 1 and Stage 2).</p>\n <p>\n Summary of results and conclusions:</p>\n <p>\n • The results of this study supported a positive benefit/risk of the primary vaccination with</p>\n <p>\n Sanofi’s monovalent and bivalent COVID-19 vaccines in individuals aged 18 to 59 years.</p>\n <p>\n While the safety profile in older adults is favorable, the limited number of cases and sample</p>\n <p>\n size did not allow demonstration of efficacy to support a positive benefit/risk in the older adult</p>\n <p>\n population.</p>\n <p>\n • This study provided evidence of cross-reactive protection against the virus variants not</p>\n <p>\n included in the vaccine.</p>\n <p>\n • No key risks (safety concerns) were identified in the adult or in the older adult population.</p>\n <p>\n • This study provided further evidence of the increased immune response and relative efficacy</p>\n <p>\n following Sanofi’s booster vaccination regardless of priming vaccine.</p>\n <p>\n Demographic and other baseline characteristics:</p>\n <p>\n Overall, the proportion of male participants was higher than the proportion of female participants</p>\n <p>\n (male to female ratio of ranged from 1.31 to 1.47). The mean age ranged from approximately 36</p>\n <p>\n to 38 years, similar across all study phases. Most participants were aged between 18 to 59 years.</p>\n <p>\n As in the primary series, most participants in the crossover and booster phases originated from</p>\n <p>\n India, Kenya, and Ghana (> 10% of participants). Participants’ race was predominantly Asian</p>\n <p>\n (Asian Indian) and Black or African American and mostly of Not Hispanic or Latino ethnicity.</p>\n <p>\n Table S4 - Demographics of the safety populations - All study phases</p>\n <p>\n Characteristics Stage 1</p>\n <p>\n N=10114</p>\n <p>\n n (%)</p>\n <p>\n Stage 2</p>\n <p>\n N=12924*</p>\n <p>\n n (%)</p>\n <p>\n All Crossover</p>\n <p>\n N=6529</p>\n <p>\n n (%)</p>\n <p>\n All Booster</p>\n <p>\n N=14237</p>\n <p>\n n (%)</p>\n <p>\n Sex: male 5727 (56.6) 7542* (58.4) 3882 (59.5) 8419 (59.1)</p>\n <p>\n Sex: female 4387 (43.4) 5382 (41.6) 2647 (40.5) 5818 (40.9)</p>\n <p>\n Age (years) mean (SD) 37.9 (13.9) 36.1 (12.9) 35.8 (11.0) 37.1 (12.3)</p>\n <p>\n Age (years) median 36.0 34.0 35.0 36.0</p>\n <p>\n Age (years) min, max 18.0; 95.0 18.0; 93.0 18.0; 84.0 18.0; 93.0</p>\n <p>\n Age 18 through 59 years 9280 (91.8) 12147* (94.0) 6428 13556</p>\n <p>\n Age ≥ 60 years 834 (8.2) 777 (6.0) 101 681</p>\n <p>\n Race: American Indian or Alaska Native 3286 (32.5) 811† (6.3) 595 (9.1) 1353 (9.5)</p>\n <p>\n Race: Asian 4445 (43.9) 5129 (39.7) 3329 (51.0) 6779 (47.6)</p>\n <p>\n Characteristics Stage 1</p>\n <p>\n N=10114</p>\n <p>\n n (%)</p>\n <p>\n Stage 2</p>\n <p>\n N=12924*</p>\n <p>\n n (%)</p>\n <p>\n All Crossover</p>\n <p>\n N=6529</p>\n <p>\n n (%)</p>\n <p>\n All Booster</p>\n <p>\n N=14237</p>\n <p>\n n (%)</p>\n <p>\n Race: Black or African American 2109 (20.9) 5727 (44.3) 2076 (31.8) 4914 (34.5)</p>\n <p>\n Race: Native Hawaiian or Other Pacific</p>\n <p>\n Islander</p>\n <p>\n 4 (<0.1) 3 (<0.1) 3 (<0.1) 6 (<0.1)</p>\n <p>\n Race: White 230 (2.3) 74 (0.6) 79 (1.2) 367 (2.6)</p>\n <p>\n Race: Multiracial 14 (0.1) 11 (<0.1) 7 (0.1) 13 (<0.1)</p>\n <p>\n Race: Not reported 4 (<0.1) 177 (1.4) 54 (0.8) 113 (0.8)</p>\n <p>\n Race: Unknown 22 (0.2) 992 (7.7) 386 (5.9) 692 (4.9)</p>\n <p>\n Ethnicity: Hispanic or Latino 3350 (33.1) 2109† (16.3) 1096 (16.8) 2285 (16.0)</p>\n <p>\n Ethnicity: Not Hispanic or Latino 6726 (66.5) 10753 (83.2) 5413 (82.9) 11898 (83.6)</p>\n <p>\n Ethnicity: Not reported 7 (<0.1) 28 (0.2) 9 (0.1) 23 (0.2)</p>\n <p>\n Ethnicity: Unknown 31 (0.3) 34 (0.3) 11 (0.2) 31 (0.2)</p>\n <p>\n Abbreviations: SD, standard deviation</p>\n <p>\n N=number of participants in the specified group. This value is used as the denominator for percentage calculations.</p>\n <p>\n n=number of participants with the specified characteristic.</p>\n <p>\n *Two participants received a vaccine at Visit 1 but whether they received the vaccine, or the placebo is unknown.</p>\n <p>\n Therefore, there is a difference of 2 participants in the total number of participants of the SafAS.</p>\n <p>\n †One of the 2 participants who had a missing information about the vaccine/placebo actually received was</p>\n <p>\n American Indian or Alaska Native. For the other participant, the race was unknown although the ethnicity was</p>\n <p>\n Hispanic or Latino.</p>\n <p>\n Source: modified from Stage 1 Brief Interim CSR Addendum, Tables 4.6 and 8.11A; Stage 2 Brief Interim CSR,</p>\n <p>\n Tables 4.11 and 8.11B; and Section 8, Table 8.14C.</p>\n <p>\n Table S5 - Baseline characteristics of safety populations – Stage 1 and Stage 2</p>\n <p>\n Characteristics Stage 1 Total</p>\n <p>\n N=10114</p>\n <p>\n n (%)</p>\n <p>\n Stage 2 Total</p>\n <p>\n N=12924</p>\n <p>\n n (%)</p>\n <p>\n All</p>\n <p>\n Crossover</p>\n <p>\n N=6529</p>\n <p>\n n (%)</p>\n <p>\n All Booster</p>\n <p>\n N=14237</p>\n <p>\n n (%)</p>\n <p>\n Increased risk for severe COVID-19:</p>\n <p>\n Yes* 3549 (35.1) 4165 (32.2) 1651 (25.3) 3987 (28.0)</p>\n <p>\n Increased risk for severe COVID-19: No* 6565 (64.9) 8759† (67.8) 4878 (74.7) 10250 (72.0)</p>\n <p>\n Age 18-59 years and at increased risk for</p>\n <p>\n severe COVID-19 2715 (26.8) 3747 (29.0) 1591 (24.8) 3593 (26.5)</p>\n <p>\n Age 18-59 years and not at increased risk</p>\n <p>\n for severe COVID-19 6565 (64.9) 8400† (65.0) 4837 (75.2) 9963 (73.5)</p>\n <p>\n Age ≥60 years and at increased risk for</p>\n <p>\n severe COVID-19 484 (4.8) 418 (3.2) 60 (59.4) 394 (57.9)</p>\n <p>\n Age ≥60 years and not at increased risk</p>\n <p>\n for severe COVID-19 350 (3.5) 359 (2.8) 41 (40.6) 287 (42.1)</p>\n <p>\n SARS-CoV-2 naïve at Day 01 2554 (25.3) 1176 (9.1) ND ND</p>\n <p>\n SARS-CoV-2 non-naïve at Day 01 7461 (73.8) 9693 (75.0) ND ND</p>\n <p>\n SARS-CoV-2 serostatus undetermined at</p>\n <p>\n Day 01 99 (1.0) 2055 (15.9)</p>\n <p>\n ND ND</p>\n <p>\n Primary Series type:</p>\n <p>\n Stage 1 NA NA 2455 (37.6) 5524 (38.8)</p>\n <p>\n Stage 2 NA NA 4074 (62.4) 8713 (61.2)</p>\n <p>\n NA: not applicable; ND: not determined</p>\n <p>\n N=number of participants in the specified group. This value is used as the denominator for percentage calculations.</p>\n <p>\n n=number of participants with the specified characteristic.</p>\n <p>\n *High-risk conditions are conditions considered to be associated with an increased risk of severe COVID-19; for</p>\n <p>\n its definitions see the clinical study protocol (Appendix 1).</p>\n <p>\n †Two participants received a vaccine at Visit 1 but whether they received the vaccine, or the placebo is unknown.</p>\n <p>\n Therefore, there is a difference of 2 participants in the total number of participants of the SafAS.</p>\n <p>\n Source: modified from Stage 1 Brief Interim CSR Addendum Table 4.9; Stage 2 Brief Interim CSR Table 4.11;</p>\n <p>\n and Section 8, Table 8.14C.</p>\n <p>\n Exposure:</p>\n <p>\n Table S6 - Exposure by analysis sets, treatment, and selected baseline characteristics</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n (N=10 114)</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 +</p>\n <p>\n B.1.351) vaccine</p>\n <p>\n (N=13 002) All Crossover</p>\n <p>\n (N=6801)</p>\n <p>\n n/M (%)</p>\n <p>\n All Booster</p>\n <p>\n (N=14237)</p>\n <p>\n n/M (%)</p>\n <p>\n Characteristic Analysis</p>\n <p>\n Set</p>\n <p>\n Vaccine</p>\n <p>\n Group</p>\n <p>\n N=5050</p>\n <p>\n n(%)</p>\n <p>\n Placebo</p>\n <p>\n Group</p>\n <p>\n N=5064</p>\n <p>\n n(%)</p>\n <p>\n Vaccine</p>\n <p>\n Group</p>\n <p>\n N=6512</p>\n <p>\n n(%)</p>\n <p>\n Placebo</p>\n <p>\n Group</p>\n <p>\n N=6490</p>\n <p>\n n(%)</p>\n <p>\n All participants SafAS 5050 5064 6472 6450 6529/6801</p>\n <p>\n (96.0)</p>\n <p>\n 14237/14237</p>\n <p>\n (100)</p>\n <p>\n All participants SafASPD1</p>\n <p>\n 5050 5064 6472 6450 6526/6529</p>\n <p>\n (>99.9)</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n (N=10 114)</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 +</p>\n <p>\n B.1.351) vaccine</p>\n <p>\n (N=13 002) All Crossover</p>\n <p>\n (N=6801)</p>\n <p>\n n/M (%)</p>\n <p>\n All Booster</p>\n <p>\n (N=14237)</p>\n <p>\n n/M (%)</p>\n <p>\n Characteristic Analysis</p>\n <p>\n Set</p>\n <p>\n Vaccine</p>\n <p>\n Group</p>\n <p>\n N=5050</p>\n <p>\n n(%)</p>\n <p>\n Placebo</p>\n <p>\n Group</p>\n <p>\n N=5064</p>\n <p>\n n(%)</p>\n <p>\n Vaccine</p>\n <p>\n Group</p>\n <p>\n N=6512</p>\n <p>\n n(%)</p>\n <p>\n Placebo</p>\n <p>\n Group</p>\n <p>\n N=6490</p>\n <p>\n n(%)</p>\n <p>\n All participants SafASPD2</p>\n <p>\n 4720 4722 5788 5755 6442/6529</p>\n <p>\n (98.7)</p>\n <p>\n All participants RSafAS 2296 2293 2433 2418</p>\n <p>\n All participants RSafASPD1</p>\n <p>\n 2296 2293 2433 2418</p>\n <p>\n All participants RSafASPD2</p>\n <p>\n 2153 2156 2276 2271</p>\n <p>\n Age: 18-59 years SafAS 4636</p>\n <p>\n (91.8)</p>\n <p>\n 4644</p>\n <p>\n (91.7)</p>\n <p>\n 6078</p>\n <p>\n (100) 6067 (100) 6428/6594</p>\n <p>\n (97.5)</p>\n <p>\n 13556/13556</p>\n <p>\n (100)</p>\n <p>\n Age: 18-59 years SafASPD1</p>\n <p>\n 4634 4644 6078 6067 6425/6428</p>\n <p>\n (>99.9)</p>\n <p>\n Age: 18-59 years SafASPD2</p>\n <p>\n 4326 4322 5441 5414 6341/6428</p>\n <p>\n (98.6)</p>\n <p>\n Age: 18-59 years RSafAS 2036</p>\n <p>\n (88.7)</p>\n <p>\n 2030</p>\n <p>\n (88.5)</p>\n <p>\n 2040</p>\n <p>\n (100) 2037 (100)</p>\n <p>\n Age: 18-59 years RSafASPD1</p>\n <p>\n 2036 2030 2040 2037</p>\n <p>\n Age: 18-59 years RSafASPD2</p>\n <p>\n 1905 1905 1930 1931</p>\n <p>\n Age: ≥ 60 years SafAS 414 (8.2) 420 (8.3) 394 (100) 383 (100) 101/207 (48.8) 681/681 (100)</p>\n <p>\n Age: ≥ 60 years SafASPD1</p>\n <p>\n 414 420 394 383 101/101 (100)</p>\n <p>\n Age: ≥ 60 years SafASPD2</p>\n <p>\n 394 400 347 341 101/101 (100)</p>\n <p>\n Age: ≥ 60 years RSafAS 260 (11.3) 263 (11.5) 393 (100) 381 (100)</p>\n <p>\n Age: ≥ 60 years RSafASPD1</p>\n <p>\n 260 263 393 381</p>\n <p>\n Age: ≥ 60 years RSafASPD2</p>\n <p>\n 248 251 346 340</p>\n <p>\n High risk</p>\n <p>\n condition: yes</p>\n <p>\n SafAS 1577</p>\n <p>\n (31.2)</p>\n <p>\n 1623</p>\n <p>\n (32.0)</p>\n <p>\n 2095</p>\n <p>\n (100) 2070 (100) 1651/6529</p>\n <p>\n (25.3)</p>\n <p>\n 3987/14237</p>\n <p>\n (28.0)</p>\n <p>\n High risk</p>\n <p>\n condition: yes</p>\n <p>\n RSafAS 741 (32.3) 771 (33.6) 869 (100) 862 (100)</p>\n <p>\n High risk</p>\n <p>\n condition: no</p>\n <p>\n SafAS 3473</p>\n <p>\n (68.8)</p>\n <p>\n 3441</p>\n <p>\n (68.0)</p>\n <p>\n 4377</p>\n <p>\n (100) 4380 (100) 4878/6529</p>\n <p>\n (74.7)</p>\n <p>\n 10250/14237</p>\n <p>\n (72.0)</p>\n <p>\n High risk</p>\n <p>\n condition: no</p>\n <p>\n RSafAS 1555</p>\n <p>\n (67.7)</p>\n <p>\n 1522</p>\n <p>\n (66.4)</p>\n <p>\n 1564</p>\n <p>\n (100) 1556 (100)</p>\n <p>\n Abbreviations: SafAS, Safety Analysis Set; RSafAS, Reactogenicity safety analysis subset.</p>\n <p>\n n: number of participants fulfilling the item listed; M: number of participants with available data for the relevant</p>\n <p>\n endpoint.</p>\n <p>\n Source: modified from Stage 1 Brief Interim CSR Table 5.15, Stage 2 Brief Interim CSR Table 5.16, Table 8.9D,</p>\n <p>\n Table 8.11C, and Table 8.14C.</p>\n <p>\n Safety results:</p>\n <p>\n Table S7 - Safety Summary – All Phases</p>\n <p>\n Blinded Primary Series</p>\n <p>\n (Primary and Secondary safety)</p>\n <p>\n Unblinded Crossover and Booster</p>\n <p>\n (Secondary safety)</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614) vaccine</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 + B.1.351) vaccine</p>\n <p>\n Crossover</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n Booster</p>\n <p>\n Monovalent (B.1.351)</p>\n <p>\n vaccine</p>\n <p>\n Immediate</p>\n <p>\n unsolicited AEs (ie,</p>\n <p>\n 30 minutes after</p>\n <p>\n vaccination)</p>\n <p>\n (number and % of</p>\n <p>\n participants in each</p>\n <p>\n group)</p>\n <p>\n AEs: 7 Vaccine; 6 Placebo</p>\n <p>\n ARs: 7 Vaccine; 2 Placebo</p>\n <p>\n (≤0.1% of participants in each group)</p>\n <p>\n 1 Grade 3 AR</p>\n <p>\n AEs: 4 Vaccine; 7 Placebo</p>\n <p>\n ARs: 4 Vaccine; 6 Placebo</p>\n <p>\n (≤0.1% of participants in each group)</p>\n <p>\n No Grade 3 events</p>\n <p>\n AEs: 3</p>\n <p>\n ARs: 3</p>\n <p>\n (<0.1% of participants)</p>\n <p>\n No Grade 3 events</p>\n <p>\n AEs: 5</p>\n <p>\n ARs: 5</p>\n <p>\n (<0.1% of participants)</p>\n <p>\n No Grade 3 events</p>\n <p>\n Solicited reactions</p>\n <p>\n within 7 days after</p>\n <p>\n any and each</p>\n <p>\n vaccination</p>\n <p>\n (% of participants in</p>\n <p>\n each group)</p>\n <p>\n 56.8% Vaccine; 35.7% Placebo</p>\n <p>\n Vaccine: 68.2% naïve; 52.2% non-naïve</p>\n <p>\n Placebo: 40.3% naïve; 33.6% non-naïve</p>\n <p>\n Most frequently reported reactions among</p>\n <p>\n Vaccine recipients:</p>\n <p>\n •Injection site pain: 44.4% (1.7% Grade 3)</p>\n <p>\n •Headache: 29.8% (2.2% Grade 3)</p>\n <p>\n •Myalgia: 28.2%</p>\n <p>\n •Malaise: 27.2%</p>\n <p>\n Lower frequencies after the 2nd vaccination.</p>\n <p>\n Intensities were similar after both vaccinations.</p>\n <p>\n Similar frequencies of overall and Grade 3</p>\n <p>\n 57.8% Vaccine; 40.9% Placebo</p>\n <p>\n Vaccine: 64.0% naïve; 55.3% non-naïve</p>\n <p>\n Placebo: 43.8% naïve; 37.6% non-naïve</p>\n <p>\n Most frequently reported reactions among</p>\n <p>\n Vaccine recipients:</p>\n <p>\n •Injection site pain: 46.2%</p>\n <p>\n (4.0% Grade 3)</p>\n <p>\n •Headache: 32.9% (4.1% Grade 3)</p>\n <p>\n •Malaise: 27.5%</p>\n <p>\n •Myalgia: 25.0%</p>\n <p>\n Slightly lower frequencies after the 2nd</p>\n <p>\n vaccination. Intensities were similar after</p>\n <p>\n Not applicable Not applicable</p>\n <p>\n Blinded Primary Series</p>\n <p>\n (Primary and Secondary safety)</p>\n <p>\n Unblinded Crossover and Booster</p>\n <p>\n (Secondary safety)</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614) vaccine</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 + B.1.351) vaccine</p>\n <p>\n Crossover</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n Booster</p>\n <p>\n Monovalent (B.1.351)</p>\n <p>\n vaccine</p>\n <p>\n reactions for all age groups (18-59, ≥ 60 and</p>\n <p>\n ≥ 65 years).</p>\n <p>\n both vaccinations.</p>\n <p>\n Similar frequencies of overall and Grade 3</p>\n <p>\n reactions for all age groups (18-59,</p>\n <p>\n ≥ 60 and ≥ 65 years).</p>\n <p>\n Unsolicited AEs</p>\n <p>\n within 21 days</p>\n <p>\n following (each)</p>\n <p>\n administration</p>\n <p>\n (% of participants in</p>\n <p>\n each group)</p>\n <p>\n AEs: 6.8% Vaccine; 6.9% Placebo</p>\n <p>\n ARs: 1.2% Vaccine; 0.6% Placebo</p>\n <p>\n Comparable frequency between the 1st and 2nd</p>\n <p>\n injection</p>\n <p>\n Comparable frequency between age groups with a</p>\n <p>\n slightly higher frequency of AEs observed in the</p>\n <p>\n ≥ 60 and ≥ 65 years age groups</p>\n <p>\n Higher frequency of AEs in naïves at baseline,</p>\n <p>\n both in Vaccine and Placebo</p>\n <p>\n Higher frequency of AEs in high-risk medical</p>\n <p>\n condition (HRMC) participants:</p>\n <p>\n •Vaccine: 9.7% with HRMC; 5.1% without</p>\n <p>\n HRMC</p>\n <p>\n •Placebo: same pattern</p>\n <p>\n Reactogenicity-like events (ie, fatigue, nausea,</p>\n <p>\n diarrhea, and injection site pruritus) were mostly</p>\n <p>\n reported</p>\n <p>\n AE leading to study discontinuation: 1 in the</p>\n <p>\n Vaccine group and 9 in the Placebo</p>\n <p>\n AEs: 6.3% Vaccine; 8.1% Placebo</p>\n <p>\n ARs: 0.8% Vaccine; 0.7% Placebo</p>\n <p>\n Comparable frequency between the 1st</p>\n <p>\n and 2nd injection</p>\n <p>\n Comparable frequency between age</p>\n <p>\n groups with a slightly higher frequency of</p>\n <p>\n AEs observed in the ≥ 60 and ≥ 65 years</p>\n <p>\n age groups</p>\n <p>\n Higher frequency of AEs in naïves at</p>\n <p>\n baseline, both in Vaccine and Placebo</p>\n <p>\n Higher frequency of AEs in HRMC</p>\n <p>\n participants:</p>\n <p>\n •Vaccine: 7.7% with HRMC; 5.6%</p>\n <p>\n without HRMC</p>\n <p>\n •Placebo: 10.4% with HRMC; 6.7%</p>\n <p>\n without HRMC</p>\n <p>\n Reactogenicity-like events (ie, cough,</p>\n <p>\n headache, nausea, and diarrhea) were</p>\n <p>\n mostly reported</p>\n <p>\n Not applicable</p>\n <p>\n For the Crossover /</p>\n <p>\n Booster, Unsolicited AEs</p>\n <p>\n were collected up to 21</p>\n <p>\n days after the booster</p>\n <p>\n vaccination.</p>\n <p>\n AEs: 3.3%</p>\n <p>\n ARs: 0.6%</p>\n <p>\n Higher frequency of AEs</p>\n <p>\n observed in the ≥ 60 years</p>\n <p>\n age group</p>\n <p>\n Higher frequency of AEs</p>\n <p>\n in HRMC participants</p>\n <p>\n Reactogenicity-like</p>\n <p>\n events (ie, injection site</p>\n <p>\n pain, injection site</p>\n <p>\n swelling, and headache)</p>\n <p>\n were most reported</p>\n <p>\n 1 participant had an AE</p>\n <p>\n leading to study</p>\n <p>\n discontinuation</p>\n <p>\n Blinded Primary Series</p>\n <p>\n (Primary and Secondary safety)</p>\n <p>\n Unblinded Crossover and Booster</p>\n <p>\n (Secondary safety)</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614) vaccine</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 + B.1.351) vaccine</p>\n <p>\n Crossover</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n Booster</p>\n <p>\n Monovalent (B.1.351)</p>\n <p>\n vaccine</p>\n <p>\n AEs leading to study discontinuation:</p>\n <p>\n 5 participants in each treatment group</p>\n <p>\n The below events are summarized up to the analysis cut-off date for the primary series and during the study for crossover and booster</p>\n <p>\n Discontinuation due</p>\n <p>\n to AEs</p>\n <p>\n 1 (<0.1%) participant in the Vaccine group and 9</p>\n <p>\n (<0.1%) in the Placebo group.</p>\n <p>\n No related AEs.</p>\n <p>\n 5 (<0.1%) participants in each treatment</p>\n <p>\n group.</p>\n <p>\n No related AEs.</p>\n <p>\n 8 (0.1%) participants</p>\n <p>\n No related AEs.</p>\n <p>\n 16 (0.1%) participants</p>\n <p>\n No related AEs.</p>\n <p>\n SAEs Comparable frequency between Vaccine and</p>\n <p>\n Placebo</p>\n <p>\n 3 participants had 4 related SAEs in the Vaccine</p>\n <p>\n Group; none in the Placebo.</p>\n <p>\n Comparable frequency between Vaccine</p>\n <p>\n and Placebo</p>\n <p>\n No related SAEs.</p>\n <p>\n 53 (0.8%) participants</p>\n <p>\n during the crossover phase</p>\n <p>\n 1 participant experienced a</p>\n <p>\n related SAE.</p>\n <p>\n 125 (0.9%) participants</p>\n <p>\n during the booster phase</p>\n <p>\n 1 participant experienced</p>\n <p>\n a related SAE.</p>\n <p>\n Deaths 9 in the Placebo group.</p>\n <p>\n No related deaths.</p>\n <p>\n 10 deaths, 4 in the Vaccine Group and 6 in</p>\n <p>\n the Placebo Group.</p>\n <p>\n No related deaths.</p>\n <p>\n 6 (<0.1%) participants</p>\n <p>\n during the crossover phase</p>\n <p>\n No related deaths.</p>\n <p>\n 21 (0.1%) participants</p>\n <p>\n during the booster phase</p>\n <p>\n No related deaths.</p>\n <p>\n AESIs Comparable frequency between Vaccine and</p>\n <p>\n Placebo</p>\n <p>\n 2 related adverse events of special interest</p>\n <p>\n (AESIs) (1 in each group)</p>\n <p>\n Low frequency of pIMDs, similar between the</p>\n <p>\n Vaccine and the Placebo Groups.</p>\n <p>\n No imbalance of thromboembolic events between</p>\n <p>\n Only 3 non-related AESIs reported by 2</p>\n <p>\n participants (1 in each group)</p>\n <p>\n No pIMDs reported.</p>\n <p>\n No imbalance of thromboembolic events</p>\n <p>\n between the Vaccine and the Placebo</p>\n <p>\n Groups.</p>\n <p>\n No myocarditis or pericarditis reported.</p>\n <p>\n 3 (<0.1%) participants</p>\n <p>\n during the crossover phase</p>\n <p>\n 1 related pIMD (myelitis</p>\n <p>\n transverse), which was also</p>\n <p>\n an SAE</p>\n <p>\n 6 (<0.1%) participants</p>\n <p>\n during the booster phase</p>\n <p>\n No related AESIs</p>\n <p>\n Blinded Primary Series</p>\n <p>\n (Primary and Secondary safety)</p>\n <p>\n Unblinded Crossover and Booster</p>\n <p>\n (Secondary safety)</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614) vaccine</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 + B.1.351) vaccine</p>\n <p>\n Crossover</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n Booster</p>\n <p>\n Monovalent (B.1.351)</p>\n <p>\n vaccine</p>\n <p>\n the Vaccine and the Placebo Groups.</p>\n <p>\n No myocarditis or pericarditis reported.</p>\n <p>\n No anaphylactic reaction/anaphylactic shock</p>\n <p>\n reported.</p>\n <p>\n No anaphylactic reaction/anaphylactic</p>\n <p>\n shock reported in the vaccine group.</p>\n <p>\n MAAES</p>\n <p>\n (% of participants in</p>\n <p>\n each group)</p>\n <p>\n Total: 7.8% Vaccine; 8.4% Placebo</p>\n <p>\n Related: 0.2% Vaccine; <0.1% Placebo</p>\n <p>\n Comparable frequency between the 1st and 2nd</p>\n <p>\n injection</p>\n <p>\n Slightly higher frequency in the ≥ 60 years</p>\n <p>\n compared to the 18-59 years age.</p>\n <p>\n Higher frequency in naïve participants and in</p>\n <p>\n participants with a HRMC.</p>\n <p>\n Total: 5.7% Vaccine; 6.0% Placebo</p>\n <p>\n Related: 0.2% Vaccine; 0.1% Placebo</p>\n <p>\n Comparable frequency between the 1st</p>\n <p>\n and 2nd injection</p>\n <p>\n Lower frequency in the 18-59 years of age</p>\n <p>\n compared to the ≥ 60 years of age.</p>\n <p>\n Higher frequency in naïve participants and</p>\n <p>\n in participants with a HRMC.</p>\n <p>\n 9.3% of participants during</p>\n <p>\n the crossover phase</p>\n <p>\n 20 events experienced by</p>\n <p>\n 16 (0.2%) participants</p>\n <p>\n assessed as related</p>\n <p>\n Comparable frequency of</p>\n <p>\n events in both age groups</p>\n <p>\n 9.0% of participants</p>\n <p>\n during the booster phase</p>\n <p>\n 20 events experienced by</p>\n <p>\n 17 (0.1%) participants</p>\n <p>\n assessed as related</p>\n <p>\n Slightly higher frequency</p>\n <p>\n in the ≥ 60 years</p>\n <p>\n compared to the 18-59</p>\n <p>\n years age.</p>\n <p>\n Virologicallyconfirmed</p>\n <p>\n SARS-CoV-2</p>\n <p>\n infections and/or</p>\n <p>\n symptomatic</p>\n <p>\n COVID-19</p>\n <p>\n No increased risk of severity of COVID-19 in the Vaccine Group. 1 (<0.1%) subject</p>\n <p>\n (confirmed infection)</p>\n <p>\n No COVID-19 cases</p>\n <p>\n (confirmed infection)</p>\n <p>\n No increased risk of severity of COVID-19</p>\n <p>\n Safety in</p>\n <p>\n participants of 18-25</p>\n <p>\n years of age</p>\n <p>\n Similar reactogenicity (solicited reactions and</p>\n <p>\n unsolicited AEs) to that of the older age groups</p>\n <p>\n (18-59 years and ≥ 60 years).</p>\n <p>\n Comparable frequency of serious adverse events</p>\n <p>\n Similar reactogenicity (solicited reactions</p>\n <p>\n and unsolicited AEs) to that of the older</p>\n <p>\n age groups (18-59 years and ≥ 60 years).</p>\n <p>\n Comparable frequency of SAEs, lower</p>\n <p>\n Not applicable</p>\n <p>\n Blinded Primary Series</p>\n <p>\n (Primary and Secondary safety)</p>\n <p>\n Unblinded Crossover and Booster</p>\n <p>\n (Secondary safety)</p>\n <p>\n Stage 1</p>\n <p>\n Monovalent (D614) vaccine</p>\n <p>\n Stage 2</p>\n <p>\n Bivalent (D614 + B.1.351) vaccine</p>\n <p>\n Crossover</p>\n <p>\n Monovalent (D614)</p>\n <p>\n vaccine</p>\n <p>\n Booster</p>\n <p>\n Monovalent (B.1.351)</p>\n <p>\n vaccine</p>\n <p>\n (SAEs) and AESIs, lower frequency of medically</p>\n <p>\n attended adverse events (MAAEs) than the older</p>\n <p>\n age groups.</p>\n <p>\n frequency of MAAEs than the older age</p>\n <p>\n groups. No AESIs.</p>\n <p>\n Frequency and</p>\n <p>\n spectrum of disease</p>\n <p>\n in episodes of</p>\n <p>\n symptomatic</p>\n <p>\n COVID-19 in</p>\n <p>\n SARS-CoV-2</p>\n <p>\n non-naïve adults</p>\n <p>\n Regardless of age group there was no evidence for higher incidence rate of hospitalized</p>\n <p>\n COVID-19, severe COVID-19, death associated with COVID-19, and occurrences of COVID-</p>\n <p>\n 19 in each severity rating on the 7-point ordinal scale in the Vaccine Group compared to the</p>\n <p>\n Placebo Group.</p>\n <p>\n Regardless of age group there was no evidence for</p>\n <p>\n higher incidence rate of hospitalized COVID-19, severe</p>\n <p>\n COVID-19, death associated with COVID-19, and</p>\n <p>\n occurrences of COVID-19 in each severity rating on the</p>\n <p>\n 7-point ordinal scale in crossover and booster</p>\n <p>\n participants. Findings were comparable to the primary</p>\n <p>\n series.</p>\n <p>\n PIMMCs are potentially immune-mediated medical conditions, also referred to as potential immune-mediated diseases (pIMDs), which are a subset of AESIs that include</p>\n <p>\n autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have an autoimmune etiology.</p>\n <p>\n Efficacy and immunogenicity results:</p>\n <p>\n Table S8 - Blinded Primary Series - Primary and Secondary Efficacy and Immunogenicity Results Summary</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n Primary Efficacy (Stage 1 only)</p>\n <p>\n To assess, in participants who were SARS-CoV-2 naïve, the</p>\n <p>\n clinical efficacy of the CoV2 preS dTM-AS03 vaccines for the</p>\n <p>\n prevention of symptomatic COVID-19 occurring ≥ 14 days</p>\n <p>\n after the second injection.</p>\n <p>\n • Occurrences of symptomatic COVID-19 • The VE was 15.3% (95% CI: -15.8; 38.2) not</p>\n <p>\n meeting the primary efficacy objective</p>\n <p>\n (ie, VE > 50% + LB of the 95.86% CI > 30%).</p>\n <p>\n o 18-59 years of age: VE was 17.9%</p>\n <p>\n (95% CI: -14.0; 40.9)</p>\n <p>\n o ≥ 60 years of age: VE was -5.0%</p>\n <p>\n (95% CI: - 251.0; 68.6)</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n Primary Efficacy (Stage 2 only)</p>\n <p>\n To assess, in all participants regardless of prior SARS-CoV-2</p>\n <p>\n infection, the clinical efficacy of the CoV2 preS dTM-AS03</p>\n <p>\n vaccines for prevention of symptomatic COVID-19 ≥ 14 days</p>\n <p>\n after the second injection.</p>\n <p>\n • Occurrences of symptomatic COVID-19 • The VE was 64.7% (95% CI: 46.6; 77.2) meeting</p>\n <p>\n the primary efficacy objective</p>\n <p>\n (ie, VE > 50% + LB of the 95% CI > 30%).</p>\n <p>\n Key Secondary Efficacy Objective (Stage 1)</p>\n <p>\n 1) To assess, in participants who were SARS CoV-2 naïve,</p>\n <p>\n the clinical efficacy of the CoV2 preS dTM-AS03 vaccines</p>\n <p>\n for prevention of the following occurring ≥ 14 days after</p>\n <p>\n the second injection:</p>\n <p>\n • Prevention of SARS-CoV-2 infection</p>\n <p>\n • Prevention of severe COVID-19</p>\n <p>\n Endpoints for secondary efficacy objective #1:</p>\n <p>\n • Occurrences of SARS-CoV-2 infection</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n Hypothesis testing for key secondary objectives, which</p>\n <p>\n was conditional to the success of the primary objective,</p>\n <p>\n was not performed.</p>\n <p>\n • VE against SARS-CoV-2 infection was 0.9% (95%</p>\n <p>\n CI: -22.2; 19.6).</p>\n <p>\n • 44.8% VE against severe COVID-19 (3 cases in the</p>\n <p>\n Vaccine Group and 5 cases in the Placebo Group).</p>\n <p>\n Key Secondary Efficacy Objective (Stage 2)</p>\n <p>\n 2) To assess:</p>\n <p>\n • Prevention of SARS-CoV-2 infection in participants</p>\n <p>\n who were SARS-CoV-2 naïve, occurring ≥ 14 days</p>\n <p>\n after the second injection</p>\n <p>\n • Prevention of severe COVID-19 in participants</p>\n <p>\n regardless of prior SARS-CoV-2 infection occurring</p>\n <p>\n ≥ 14 days after the second injection</p>\n <p>\n Endpoints for secondary efficacy objective #2:</p>\n <p>\n • Occurrences of SARS-CoV-2 infection</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n • VE against SARS-CoV-2 infection was 9.6% (95%</p>\n <p>\n CI: -16.4; 29.9) not meeting the key secondary</p>\n <p>\n efficacy objective (ie, LB of 95% CI was < 0%).</p>\n <p>\n • Hypothesis testing for this key secondary objective</p>\n <p>\n was conditional to the success of the primary</p>\n <p>\n objective and the collection of 22 severe cases. Yet,</p>\n <p>\n fewer than 22 severe COVID-19 cases were</p>\n <p>\n collected, and hypothesis testing was not performed.</p>\n <p>\n The very limited cases count (3 cases in the Vaccine</p>\n <p>\n Group and 2 cases in the Placebo Group) precluded</p>\n <p>\n any definite conclusion about efficacy against</p>\n <p>\n severe COVID-19.</p>\n <p>\n Other Secondary Efficacy Objectives</p>\n <p>\n 3) To assess, in participants who were SARS-CoV-2 naïve,</p>\n <p>\n the clinical efficacy of the CoV2 preS dTM-AS03 vaccines</p>\n <p>\n for the prevention of symptomatic COVID-19 occurring</p>\n <p>\n ≥ 14 days after the first injection.</p>\n <p>\n Endpoint for secondary efficacy objective #3:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n Stage 1:</p>\n <p>\n • VE (PD1) against symptomatic COVID-19 was</p>\n <p>\n 34.1% with 88 cases in the Vaccine Group and 124</p>\n <p>\n in the Placebo Group</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n Stage 2:</p>\n <p>\n • VE (PD1) against symptomatic COVID-19 was</p>\n <p>\n 38.2% with 30 cases in the Vaccine Group and 48 in</p>\n <p>\n the Placebo Group</p>\n <p>\n 4) Stage 1 only: To assess, in all participants regardless of</p>\n <p>\n prior SARS-CoV-2 infection, the clinical efficacy of the</p>\n <p>\n CoV2 preS dTM-AS03 vaccines for:</p>\n <p>\n • Prevention of symptomatic COVID-19</p>\n <p>\n • Prevention of severe COVID-19</p>\n <p>\n Stage 1 only: Endpoints for secondary efficacy objective</p>\n <p>\n #4:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n • VE against symptomatic COVID-19 ranged</p>\n <p>\n between 32.9% PD2 (126 cases in the Vaccine</p>\n <p>\n Group and 182 in the Placebo Group) and 40.7%</p>\n <p>\n PD1 (137 cases in the Vaccine Group and 225 in the</p>\n <p>\n Placebo Group)</p>\n <p>\n • VE against severe COVID-19 ranged between</p>\n <p>\n 39.4% PD2 (5 cases in the Vaccine Group and 8 in</p>\n <p>\n the Placebo Group) and 61.0% PD1 (6 cases in the</p>\n <p>\n Vaccine Group and 15 in the Placebo Group)</p>\n <p>\n 5) To assess, in participants who are SARS-CoV-2 non-naïve,</p>\n <p>\n the clinical efficacy of the CoV2 preS dTM-AS03 vaccines</p>\n <p>\n for:</p>\n <p>\n • Prevention of symptomatic COVID-19</p>\n <p>\n • Prevention of severe COVID-19</p>\n <p>\n Endpoints for secondary efficacy objective #5:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n Stage 1:</p>\n <p>\n • VE against symptomatic COVID-19 ranged</p>\n <p>\n between 52.7% PD2 (43 cases in the Vaccine Group</p>\n <p>\n and 90 in the Placebo Group) and 52.2% PD1 (48</p>\n <p>\n cases in the Vaccine Group and 100 in the Placebo</p>\n <p>\n Group).</p>\n <p>\n • VE against severe COVID-19 was not meaningful</p>\n <p>\n as there were few cases both PD1 (3 cases in the</p>\n <p>\n Vaccine Group and 2 in the Placebo Group) and</p>\n <p>\n PD2 (2 cases in each treatment group).</p>\n <p>\n Stage 2:</p>\n <p>\n • VE against symptomatic COVID-19 ranged</p>\n <p>\n between 75.1% PD2 (16 cases in the Vaccine Group</p>\n <p>\n and 63 in the Placebo Group and 75.9% PD1 (26</p>\n <p>\n cases in the Vaccine Group and 106 in the Placebo</p>\n <p>\n Group).</p>\n <p>\n • There were only 2 cases of severe COVID-19 at</p>\n <p>\n PD1 and 1 case at PD2 in the Placebo Group.</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n 6) To assess, in participants who were SARS-CoV-2 naïve,</p>\n <p>\n the clinical efficacy of the CoV2 preS dTM-AS03 vaccines</p>\n <p>\n for the prevention of asymptomatic SARS-CoV-2</p>\n <p>\n infection.</p>\n <p>\n Endpoint for secondary efficacy objective #6:</p>\n <p>\n • Occurrences of asymptomatic SARS-CoV-2 infection</p>\n <p>\n Stage 1:</p>\n <p>\n • VE against asymptomatic SARS-CoV-2 infection</p>\n <p>\n was ≤ 4.5%</p>\n <p>\n Stage 2:</p>\n <p>\n • VE against asymptomatic SARS-CoV-2 infection</p>\n <p>\n was ≤ 1.2% (PD1 and PD2) with 275 cases in the</p>\n <p>\n Vaccine Group and 266 in the Placebo Group at</p>\n <p>\n PD1; and with 100 cases in the Vaccine Group and</p>\n <p>\n 107 cases in the Placebo Group at PD2</p>\n <p>\n 7) To assess the impact of the CoV2 preS dTM-AS03</p>\n <p>\n vaccines in the reduction of viral burden and shedding</p>\n <p>\n among participants with symptomatic COVID-19.</p>\n <p>\n Endpoints for secondary efficacy objective #7:</p>\n <p>\n • Viral copies/mL in respiratory samples collected at</p>\n <p>\n each follow-up timepoint</p>\n <p>\n • Number of days with positive NAAT</p>\n <p>\n • Occurrences of positive NAAT in respiratory samples</p>\n <p>\n at each follow-up timepoint during symptomatic</p>\n <p>\n COVID-19</p>\n <p>\n • Not applicable as not analyzed</p>\n <p>\n 8) To assess, in all participants regardless of prior SARSCoV-</p>\n <p>\n 2 infection and in participants who are SARS-CoV-2</p>\n <p>\n non-naïve and naïve, clinical efficacy of the CoV2 preS</p>\n <p>\n dTM-AS03 vaccines for:</p>\n <p>\n • Prevention of CDC-defined COVID-19</p>\n <p>\n • Prevention of hospitalized COVID-19</p>\n <p>\n • Prevention of symptomatic COVID-19 with severity</p>\n <p>\n of moderate COVID-19 or worse (composite endpoint</p>\n <p>\n of moderate or severe COVID-19)</p>\n <p>\n Endpoints for secondary efficacy objective #8:</p>\n <p>\n • Occurrences of CDC-defined COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Occurrences of symptomatic COVID-19 with severity</p>\n <p>\n of moderate COVID-19 or worse (composite endpoint</p>\n <p>\n of at least one of moderate or severe COVID-19)</p>\n <p>\n Stage 1:</p>\n <p>\n • VE (PD2) against CDC-defined COVID-19 was</p>\n <p>\n 30.2% with 131 cases in the Vaccine Group and 182</p>\n <p>\n in the Placebo Group.</p>\n <p>\n • VE (PD2) against hospitalized symptomatic</p>\n <p>\n COVID-19 was 100%, with a limited case count (ie,</p>\n <p>\n 0 in the Vaccine Group; 5 in the Placebo Group)</p>\n <p>\n • VE (PD2) against symptomatic COVID-19 with</p>\n <p>\n severity of moderate or worse was 55.6% with 11</p>\n <p>\n cases in the Vaccine Group and 24 in the Placebo</p>\n <p>\n Group.</p>\n <p>\n Stage 2:</p>\n <p>\n • VE (PD2) against CDC-defined COVID-19 was</p>\n <p>\n 65.4% with 31 cases in the Vaccine Group and 88 in</p>\n <p>\n the Placebo Group</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n • VE (PD2) against hospitalized symptomatic</p>\n <p>\n COVID-19 was 100%, with a limited case count (ie,</p>\n <p>\n 0 in the Vaccine Group; 2 in the Placebo Group)</p>\n <p>\n • VE (PD2) against symptomatic COVID-19 with</p>\n <p>\n severity of moderate or worse was 29.9%, with a</p>\n <p>\n limited case count (ie, 5 in the Vaccine Group; 7 in</p>\n <p>\n the Placebo Group)</p>\n <p>\n 9) To assess the durability of clinical efficacy of the CoV2</p>\n <p>\n preS dTM-AS03 vaccines over time in SARS-CoV-2 naïve</p>\n <p>\n participants against:</p>\n <p>\n • SARS-CoV-2 infection</p>\n <p>\n • Asymptomatic SARS-CoV-2 infection</p>\n <p>\n Endpoints for secondary efficacy objective #9:</p>\n <p>\n • Occurrences of SARS-CoV-2 infection</p>\n <p>\n • Occurrences of asymptomatic SARS-CoV-2 infection</p>\n <p>\n • Not applicable as not analyzed</p>\n <p>\n 10) To assess the durability of clinical efficacy of the CoV2</p>\n <p>\n preS dTM-AS03 vaccines over time in all participants and</p>\n <p>\n by prior SARS-CoV-2 infection (naïve and non-naïve) for:</p>\n <p>\n • Prevention of symptomatic COVID-19</p>\n <p>\n • Prevention of severe COVID-19</p>\n <p>\n • Prevention of CDC-defined COVID-19</p>\n <p>\n • Prevention of hospitalized COVID-19</p>\n <p>\n Endpoints for secondary efficacy objective #10:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrences of severe COVID-19</p>\n <p>\n • Occurrences of CDC-defined COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Not applicable as not analyzed</p>\n <p>\n 11) To assess, in participants who are SARS-CoV-2 naïve, the</p>\n <p>\n clinical efficacy of the CoV2 preS dTM-AS03 vaccines for</p>\n <p>\n the prevention of symptomatic COVID-19 occurring ≥ 7</p>\n <p>\n days after the second injection.</p>\n <p>\n Endpoint for secondary efficacy objective #11:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Not applicable as not analyzed</p>\n <p>\n 12) Stage 2 only: To assess, in participants who are SARSCoV-</p>\n <p>\n 2 naïve, the clinical efficacy of the CoV2 preS dTMAS03</p>\n <p>\n vaccines for:</p>\n <p>\n • Prevention of symptomatic COVID-19</p>\n <p>\n • Prevention of severe COVID-19</p>\n <p>\n Stage 2 only: Endpoint for secondary efficacy objective</p>\n <p>\n #12:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n • VE against symptomatic COVID-19 was 30.9%</p>\n <p>\n with 15 cases in the Vaccine Group and 22 in the</p>\n <p>\n Placebo Group.</p>\n <p>\n • the limited case count for severe COVID-19, ie, 3</p>\n <p>\n cases in the Vaccine Group and 1 in the Placebo</p>\n <p>\n Group, precludes any definite conclusion</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n Secondary Immunogenicity</p>\n <p>\n 1) To compare the neutralizing antibody response 21 days</p>\n <p>\n after last vaccination (D43) to the D614G variant between</p>\n <p>\n the monovalent and bivalent vaccines in SARS-CoV-2</p>\n <p>\n naïve and non-naïve participants in the Random</p>\n <p>\n Immunogenicity Subcohort.</p>\n <p>\n 2) To compare the neutralizing antibody response 21 days</p>\n <p>\n after last vaccination (D43) to the Beta (B.1.351) variant</p>\n <p>\n between the monovalent and bivalent vaccines in SARSCoV-</p>\n <p>\n 2 naïve and non-naïve participants in the Random</p>\n <p>\n Immunogenicity Subcohort.</p>\n <p>\n 3) To compare the neutralizing antibody response 21 days</p>\n <p>\n after last vaccination (D43) to the Beta (B.1.351) variant in</p>\n <p>\n the bivalent vaccine group and the neutralizing antibody</p>\n <p>\n response to the D614G variant in the monovalent vaccine</p>\n <p>\n group in SARS-CoV-2 naïve and non-naïve participants in</p>\n <p>\n the Random Immunogenicity Subcohort.</p>\n <p>\n Endpoints for secondary immunogenicity objectives #1</p>\n <p>\n - 3:</p>\n <p>\n • Individual serum neutralizing titer at D01 and D43</p>\n <p>\n • Responders, defined as participants who had</p>\n <p>\n baseline values below lower limit of quantification</p>\n <p>\n (LLOQ) with quantifiable neutralization titer above</p>\n <p>\n assay LLOQ at each pre-defined post-vaccination</p>\n <p>\n time point and participants with baseline values</p>\n <p>\n above LLOQ with a 4-fold increase in neutralizing</p>\n <p>\n antibody titers at each pre-defined post-vaccination</p>\n <p>\n time point</p>\n <p>\n • Seroresponse, defined as a 4-fold or greater rise in</p>\n <p>\n serum neutralization titer [pre/post] at D43 relative</p>\n <p>\n to D01</p>\n <p>\n • Not applicable as not analyzed</p>\n <p>\n The following objectives were assessed in participants</p>\n <p>\n regardless of prior SARS-CoV-2 infection and in SARS-CoV-2</p>\n <p>\n non-naïve and naïve participants.</p>\n <p>\n 4) To describe the neutralizing antibody profile at D01, D22,</p>\n <p>\n D43, D78, D134, D202, D292, and D387 in each study</p>\n <p>\n group for participants in the Random Immunogenicity</p>\n <p>\n Subcohort.</p>\n <p>\n 5) To describe the neutralizing antibody profile at D01, D22,</p>\n <p>\n D43, D78, D134, D202, D292, and D387 in each study</p>\n <p>\n group for participants aged 18-25 years in the Random</p>\n <p>\n Immunogenicity Subcohort.</p>\n <p>\n 6) To describe the association of neutralizing antibody</p>\n <p>\n responses and the risk of symptomatic COVID-19.</p>\n <p>\n 7) To describe the association of neutralizing antibody</p>\n <p>\n responses and the risk of SARS-CoV-2 infection.</p>\n <p>\n Endpoints for secondary immunogenicity objectives #4</p>\n <p>\n - 9:</p>\n <p>\n Neutralizing antibody titers were measured in</p>\n <p>\n participants for each study group against the D614G and</p>\n <p>\n B.1.351 variants.</p>\n <p>\n • Individual serum neutralizing titer at each predefined</p>\n <p>\n time point</p>\n <p>\n • Individual serum neutralization titer fold-rise postvaccination</p>\n <p>\n relative to D01 at each pre-defined time</p>\n <p>\n point</p>\n <p>\n • 2-fold rise and 4-fold-rise in serum neutralization</p>\n <p>\n titer [post/pre] (fold rise ≥ 2 and ≥ 4) at each predefined</p>\n <p>\n post-vaccination timepoint</p>\n <p>\n • Responders, defined as participants who had</p>\n <p>\n baseline values below LLOQ with quantifiable</p>\n <p>\n Immunogenicity objectives #6 to #9 were not assessed.</p>\n <p>\n Stage 1:</p>\n <p>\n The immunogenicity objectives were evaluated in 1956</p>\n <p>\n participants. By the data cut-off date only neutralizing</p>\n <p>\n Ab data against the D614G variant</p>\n <p>\n were available.</p>\n <p>\n • At D43, the percentage of responders in terms of</p>\n <p>\n D614 neutralizing antibodies was 97.0% for naïve</p>\n <p>\n participants, 77.0% for non-naïve participants, and</p>\n <p>\n 87.9% for All participants.</p>\n <p>\n • At D43, neutralizing Ab GMTs against D614 in</p>\n <p>\n adults 18 years and older were higher in non-naïve</p>\n <p>\n participants (GMT: 9239) compared to naïve</p>\n <p>\n participants (GMT: 1461). This pattern was</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n 8) To describe the association of neutralizing antibody</p>\n <p>\n responses and the risk of other COVID-19 disease</p>\n <p>\n endpoints.</p>\n <p>\n 9) To evaluate the immunological correlates of risk and</p>\n <p>\n correlates of protection against symptomatic COVID-19,</p>\n <p>\n SARS-CoV-2 infection, and other COVID-19 disease</p>\n <p>\n endpoints.</p>\n <p>\n neutralization titer above assay LLOQ at each predefined</p>\n <p>\n post-vaccination time point and participants</p>\n <p>\n with baseline values above LLOQ with a 4-fold</p>\n <p>\n increase in neutralizing antibody titers at each predefined</p>\n <p>\n post-vaccination timepoint</p>\n <p>\n observed in the 18 to 59 years and the ≥ 60 years</p>\n <p>\n age groups.</p>\n <p>\n • Neutralizing Ab GMTs against D614 were generally</p>\n <p>\n higher in all participants (regardless of prior SARSCoV-</p>\n <p>\n 2 infection) aged 18 to 25 years (GMT: 5164)</p>\n <p>\n and 18 to 59 years (GMT: 4252) compared to</p>\n <p>\n individuals aged ≥ 60 years (GMT: 1281) and ≥ 65</p>\n <p>\n years (GMT: 815). Neutralizing Ab GMTs in nonnaive</p>\n <p>\n participants were comparable across agegroups.</p>\n <p>\n Stage 2:</p>\n <p>\n • Not applicable as not analyzed</p>\n <p>\n Abbreviations: CI, confidence interval; D, day; GMT, geometric mean titer; IRR, incidence rate ratio LB, lower bound; LLOQ, lower limit of quantification; PD1, post-dose 1;</p>\n <p>\n PD2, post-dose 2.</p>\n <p>\n Table S9 - Unblinded Crossover/Booster - Secondary Immunogenicity and Exploratory Efficacy Results Summary</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n Secondary Immunogenicity</p>\n <p>\n To describe the neutralizing antibody profile at D01 and</p>\n <p>\n at 21 days and 6 months after last crossover injection in</p>\n <p>\n the placebo group and booster injection in each study</p>\n <p>\n group for participants in the Random Immunogenicity</p>\n <p>\n Subcohort.</p>\n <p>\n Endpoints for secondary immunogenicity objective:</p>\n <p>\n Neutralizing antibody titers were measured in</p>\n <p>\n participants for each study group against the D614G and</p>\n <p>\n B.1.351 variants.</p>\n <p>\n • Individual serum neutralizing titer at each predefined</p>\n <p>\n time point</p>\n <p>\n • Individual serum neutralization titer fold-rise postvaccination</p>\n <p>\n relative to D01 at each pre-defined time</p>\n <p>\n point</p>\n <p>\n • 2-fold rise and 4-fold-rise in serum neutralization</p>\n <p>\n titer [post/pre] (fold rise ≥ 2 and ≥ 4) at each predefined</p>\n <p>\n post-vaccination timepoint</p>\n <p>\n • Responders, defined as participants who had</p>\n <p>\n baseline values below LLOQ with quantifiable</p>\n <p>\n neutralization titer above assay LLOQ at each</p>\n <p>\n pre-defined post-vaccination time point and</p>\n <p>\n participants with baseline values above LLOQ with</p>\n <p>\n a 4-fold increase in neutralizing antibody</p>\n <p>\n Crossover participants</p>\n <p>\n For both D614G and B.1.351 variants, Ab titers increased 21</p>\n <p>\n days post-dose 2 of primary vaccination (D43) and 21 days</p>\n <p>\n after booster vaccination (D163) while remaining sustained</p>\n <p>\n at 6 months after booster vaccination (D322).</p>\n <p>\n Across variants, over 55% of participants were responders at</p>\n <p>\n D43, whereas around 50% of the participants were</p>\n <p>\n responders at D163 and D322.</p>\n <p>\n Booster participants</p>\n <p>\n For both D614G and B.1.351 variants, Ab titers increased</p>\n <p>\n 21 days after booster vaccination (D22/D163) and remained</p>\n <p>\n over baseline levels 6 months after booster vaccination</p>\n <p>\n (D202/D322).</p>\n <p>\n Across variants, the percentage of responders was ≤35% at</p>\n <p>\n D22/D163 and ≤20% at D202/D322.</p>\n <p>\n Exploratory Efficacy</p>\n <p>\n 1) To describe the relative efficacy ≥ 6 months after a</p>\n <p>\n booster dose among participants initially in the</p>\n <p>\n Vaccine group (earlier booster) versus the efficacy</p>\n <p>\n ≥ 14 days after a booster dose in participants</p>\n <p>\n initially in the Placebo group (later booster).</p>\n <p>\n Endpoints for exploratory efficacy objective #1:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n Between the 2 groups, the relative efficacy (1-IRR) was</p>\n <p>\n 6.5% (95% CI: -60.1; 46.2) against symptomatic COVID-19</p>\n <p>\n and 32.7% (95% CI: -1193.2; 98.9) against severe COVID-</p>\n <p>\n 19. For hospitalized COVID-19, there were 2 cases in the</p>\n <p>\n earlier booster group and none in the later booster group.</p>\n <p>\n 2) To describe the relative efficacy ≥ 14 days after a</p>\n <p>\n booster dose among initial vaccine recipients versus</p>\n <p>\n ≥ 14 days after the primary series among initial</p>\n <p>\n placebo recipients.</p>\n <p>\n Endpoints for exploratory efficacy objective #2:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n Between the 2 groups, the relative efficacy (1-IRR) was</p>\n <p>\n 69.5% (95% CI: 50.5; 81.9) against symptomatic COVID-</p>\n <p>\n 19, 72.6% (95 CI: -177.0; 99.4) against severe COVID-19,</p>\n <p>\n and 100% (CI: -485.1; 100.0) against hospitalized COVID-</p>\n <p>\n 19.</p>\n <p>\n Objectives Endpoints Results Summary</p>\n <p>\n 3) To describe the relative efficacy ≥ 14 days after a</p>\n <p>\n booster dose among participants initially vaccinated</p>\n <p>\n with the monovalent CoV2 preS dTM-AS03</p>\n <p>\n (D614) vaccine (Vaccine group Stage 1) versus the</p>\n <p>\n efficacy ≥ 14 days after a booster dose in</p>\n <p>\n participants initially vaccinated with the bivalent</p>\n <p>\n CoV2 preS dTM-AS03 (D614+B.1351) vaccine</p>\n <p>\n (Vaccine group Stage 2).</p>\n <p>\n Endpoints for exploratory efficacy objective #3:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n Between the 2 groups, the relative efficacy (1-IRR) was -</p>\n <p>\n 131.1% (95 CI: -275.6; -44.1) against symptomatic COVID-</p>\n <p>\n 19 and -49.3% (95% CI: -1959; 89.2) against severe</p>\n <p>\n COVID-19. For hospitalized COVID-19, there was 1 case in</p>\n <p>\n the earlier booster group and 1 case in the later booster</p>\n <p>\n group.</p>\n <p>\n 4) To describe the relative efficacy≥ 14 days after a</p>\n <p>\n booster dose among participants who received the</p>\n <p>\n CoV2 preS dTM-AS03 primary vaccination series</p>\n <p>\n versus the efficacy ≥ 14 days after a booster dose in</p>\n <p>\n participants who received authorized/approved</p>\n <p>\n vaccines primary vaccination series in the initial</p>\n <p>\n Placebo Group.</p>\n <p>\n Endpoints for exploratory efficacy objective #4:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Occurrence of severe COVID-19</p>\n <p>\n Between the 2 groups, the relative efficacy (1-IRR) was</p>\n <p>\n 91.9% (95% CI: 83.6; 96.1) against symptomatic COVID-19</p>\n <p>\n and 89.9% (95% CI: -693.2; 99.9) against severe COVID-</p>\n <p>\n 19. There were no cases of hospitalized COVID-19 in either</p>\n <p>\n group.</p>\n <p>\n 5) To describe the relative efficacy ≥ 14 days after a</p>\n <p>\n booster dose among participants with longer</p>\n <p>\n interval between primary series and booster (initial</p>\n <p>\n Vaccine group) versus the efficacy ≥ 14 days after a</p>\n <p>\n booster dose in participants with a shorter interval</p>\n <p>\n between primary series and booster (initial Placebo</p>\n <p>\n group).</p>\n <p>\n Endpoints for exploratory efficacy objective #5:</p>\n <p>\n • Occurrences of symptomatic COVID-19</p>\n <p>\n • Occurrences of hospitalized COVID-19</p>\n <p>\n • Occurrence of severe COVID-9</p>\n <p>\n Between the 2 groups, the relative efficacy (1-IRR) was -</p>\n <p>\n 33.1% (95% CI: -103.3; 11.3) against symptomatic COVID-</p>\n <p>\n 19 and -21.3% (95% CI: -1240.9; 82.6) against severe</p>\n <p>\n COVID-19. For hospitalized COVID-19, there were 2 cases</p>\n <p>\n in the initial Vaccine group and none in the initial Placebo</p>\n <p>\n group.</p>\n <p>\n Exploratory Immunogenicity • Not applicable as not analyzed</p>\n <p>\n Abbreviations: CI, confidence interval; D, day; IRR, incidence rate ratio; LLOQ, lower limit of quantification</p>\n <p>\n Conclusions:</p>\n <p>\n • The results of this study supported a positive benefit/risk of the primary vaccination with</p>\n <p>\n Sanofi’s monovalent and bivalent COVID-19 vaccines in individuals aged 18 to 59 years.</p>\n <p>\n While the safety profile in older adults is favorable, the limited number of cases and sample</p>\n <p>\n size did not allow demonstration of efficacy to support a positive benefit/risk in the older adult</p>\n <p>\n population.</p>\n <p>\n • This study provided evidence of cross-reactive protection against the virus variants not</p>\n <p>\n included in the vaccine.</p>\n <p>\n • No safety concerns were identified in the adult or in the older adult population.</p>\n <p>\n • This study provided further evidence of the increased immune response and relative efficacy</p>\n <p>\n following Sanofi’s booster vaccination regardless of priming vaccine.</p>\n <p>\n Date and version of this report:</p>\n <p>\n Document version Date Description</p>\n <p>\n Final CSR v1.0 11-March-2025 Brief summary of Stage 1 and Stage 2 results and description of</p>\n <p>\n Crossover / Booster findings</p>\n <p>\n Brief Interim CSR Stage 2 21-July-2022 Summary of Stage 2 key results for efficacy from 14 days postinjection</p>\n <p>\n 1 and post-injection 2 up to the analysis cut-off date</p>\n <p>\n (15 March 2022), and safety up to the analysis cut-off date</p>\n <p>\n Brief Interim CSR Stage 1</p>\n <p>\n Addendum</p>\n <p>\n 11-July-2022 Summary of Stage 1 key results for efficacy from 14 days postinjection</p>\n <p>\n 1 and post-injection 2 up to the analysis cut-off date</p>\n <p>\n (28 January 2022), immunogenicity up to 21 days post-injection</p>\n <p>\n 2, and safety up to the analysis cut-off date</p>\n <p>\n Brief Interim CSR Stage 1 11-March-2022</p>\n <p>\n  </p>\n</div>\n<div>\n 36</div>\n
      • implication_results<ul>\n <li>\n The results of this study supported a positive benefit/risk of the primary vaccination with Sanofi’s monovalent and bivalent COVID-19 vaccines in individuals aged 18 to 59 years.</li>\n <li>\n While the safety profile in older adults is favorable, the limited number of cases and sample size did not allow demonstration of efficacy to support a positive benefit/risk in the older adult population.</li>\n <li>\n This study provided evidence of cross-reactive protection against the virus variants not included in the vaccine.</li>\n <li>\n No safety concerns were identified in the adult or in the older adult population.</li>\n <li>\n This study provided further evidence of the increased immune response and relative efficacy following Sanofi’s booster vaccination regardless of priming vaccine.</li>\n</ul>\n
      • quantity_imported1253
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      • final_date2025-09-03 10:05:39
      • modified2025-09-03 10:09:56
      • created2021-06-09 10:06:36
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        • id658
        • application_id1012
        • given_nameVidelis
        • middle_name
        • family_nameNduba
        • qualificationMBChB,MPH,PhD
        • professional_addressCentre for Respiratory Diseases Research, Kenya Medical Research Institute, P.O.Box 47855-00100G.P.O., Nairobi.
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2021-06-09 11:01:01
        • modified2021-09-08 10:32:07
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        • id907
        • application_id1012
        • county_id47
        • site_nameKenya Medical Research Institute
        • physical_addressKEMRI (CRDR) Clinical Research Annex, KNH Complex, Off Hospital Road, Behind Government Chemist
        • contact_detailsP. O. Box47855-00100, Nairobi, Kenya
        • contact_personDr. Videlis Nduba
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        • created2021-06-09 11:01:01
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          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
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        • application_id1012
        • county_id35
        • site_nameKEMRI/Walter Reed Project Research Center-Kericho
        • physical_addressKEMRI/WRP CRC, Hospital Road
        • contact_detailsPO Box 1357, Kericho, Rift Valley, 20200, Kenya
        • contact_personDr. Fredrick Sawe
        • site_capacity(null)
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        • created2021-06-22 16:37:24
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          • created2012-06-15 10:26:16
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        • county_id42
        • site_nameKEMRI-UAMRD-A/K, Kombewa Clinical Research Center-Kisumu
        • physical_addressOff Kisumu-Bondo Road, Opposite Kombewa County Hospita
        • contact_detailsP. O. Box 54-40100 Kisumu, Kenya
        • contact_personLucas Tina
        • site_capacity(null)
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        • created2021-06-22 16:37:24
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          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 3(array)
        • id954
        • application_id1012
        • county_id1
        • site_nameGanjoni Clinic – Mombasa
        • physical_addressUniversity of Washington/University of Nairobi, Mombasa
        • contact_detailsP. O. Box 91276-80103 Mombasa
        • contact_personDr. Kishorchandra Mandaliya
        • site_capacity(null)
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        • County(array)
          • id1
          • county_nameMombasa
          • created2012-05-31 16:15:11
          • modified2012-07-09 13:06:23
      • 4(array)
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        • application_id1012
        • county_id22
        • site_nameKEMRI/CCR Partners in Health R&D (PHRD)-Thika
        • physical_addressKEMRI-CCR-PHRD (Thika) Project OAU road, Section 9 Thika
        • contact_detailsP.O Box 19865 - 00202 Nairobi
        • contact_personDr. Nelly Mugo
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          • created2012-06-15 10:24:37
          • modified2012-06-15 10:24:37
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        • id956
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        • site_nameKenya Medical Research Institute
        • physical_addressKenya Medical Research institute, Kisumu Clinical research site, JOOTRH off Kakamega road
        • contact_detailsP. O. Box 1578 Kisumu
        • contact_personDr. Samuel Gurrion Ouma
        • site_capacity(null)
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          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 6(array)
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        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressMoi University Clinical Research Centre (MUCRC), Chandaria Cancer and Chronic Diseases Centre (CCCDC) at Moi Teaching and Referral Hospital (MTRH) Nandi Road
        • contact_detailsP.O. Box 4606 Eldoret, Rift Valley, 30100
        • contact_personAbraham Siika
        • site_capacity(null)
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        • created2021-06-22 16:37:24
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          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
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        • site_nameAga Khan University Hospital-Nairobi
        • physical_address3rd Parklands Avenue
        • contact_detailsP.O.Box 30270-00100 GPO, Nairobi, Kenya
        • contact_personDr. Saleh Mansoor
        • site_capacity(null)
        • misc(null)
        • created2021-06-22 16:37:24
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          • id47
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          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
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        • application_id1012
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        • site_nameKEMRI CCR-Butere County Hospital Site- Butere
        • physical_addressKEMRI CCR- Butere County Hospital
        • contact_detailsP.O. Box 40-50101 Butere, Kenya
        • contact_personDr. Janet Oyieko
        • site_capacity(null)
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        • created2021-06-22 16:37:24
        • modified2021-09-08 10:32:07
        • County(array)
          • id37
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          • created2012-06-15 10:26:29
          • modified2012-06-15 10:26:29
    • Sponsor(array)
      • 0(array)
        • id503
        • application_id1012
        • sponsorSanofi Pasteur
        • sponsor_typeOthers
        • contact_personJames Okwach
        • addressDiscovery Drive, Swiftwater, PA 18370-0187, USA
        • telephone_number+254717721518
        • fax_number
        • cell_number+254717721518
        • email_addressOkwachJames@praintl.com
        • created2021-06-09 11:01:01
        • modified2021-09-08 10:32:07
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PHP Environment

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      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php