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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1183-5525 | Other Identifier | World Health Organization Universal Trial Number | |
| DFI15130 | Other Identifier | Sanofi K.K. |
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| Name | Class |
|---|---|
| Sanofi | INDUSTRY |
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This phase I/II, randomized, modified double-blind, multi-center study assessed the safety and immunogenicity of a high-dose Quadrivalent influenza vaccine (QIV-HD) in older adults (greater than or equal to [>=] 65 years).
This phase I/II, randomized, modified double-blind, multi-center study was conducted in 175 healthy Japanese adults aged 65 years and older to describe the safety profile and immune responses (geometric mean titers and seroconversion for the 4 common strains at 28 days post-vaccination) of the QIV-HD administered by intramuscular (IM) and subcutaneous (SC) methods. A local standard-dose Quadrivalent Influenza Vaccine (QIV-SD) administered by SC method served as a control arm.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: QIV-HD by IM | Experimental | Participants were randomized to receive a single 0.7-milliliter (mL) injection of QIV-HD by IM route on Day 0. |
|
| Cohort 1: QIV-HD by SC | Experimental | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
|
| Cohort 2: QIV-HD by IM | Experimental | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. |
|
| Cohort 2: QIV-HD by SC | Experimental | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
|
| Cohort 2: QIV-SD by SC | Active Comparator | Participants were randomized to receive a single 0.5 mL injection of QIV-SD by SC route on Day 0. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QIV-HD by IM | Biological | IM, injected into the upper arm (deltoid area) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Immediate Unsolicited Adverse Events (AE) After Vaccination | An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of symptom and/or onset post-vaccination. Unsolicited AEs includes both serious and non-serious unsolicited AEs. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. | Within 30 minutes after vaccination |
| Number of Participants With Solicited Injection Site and Systemic Reactions | A solicited reaction was an adverse reaction observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions: pain, erythema, swelling, induration, and bruising. Solicited systemic reactions: fever, headache, malaise, myalgia, and shivering. | Within 7 days after vaccination |
| Number of Participants With Unsolicited Adverse Events After Vaccination | An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | Within 28 days after vaccination |
| Number of Participant With Serious Adverse Events (SAEs) After Vaccination |
| Measure | Description | Time Frame |
|---|---|---|
| Cohort 2: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD | GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using a hemagglutination inhibition (HAI) assay. | Day 0 (pre-vaccination) and Day 28 (post-vaccination) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Sanofi Pasteur, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanofi Pasteur Investigational Site | ÅŒsaka | Japan | ||||
| Sanofi Pasteur Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31634025 | Background | Sanchez L, Matsuoka O, Inoue S, Inoue T, Meng Y, Nakama T, Kato K, Pandey A, Chang LJ. Immunogenicity and safety of high-dose quadrivalent influenza vaccine in Japanese adults >/=65 years of age: a randomized controlled clinical trial. Hum Vaccin Immunother. 2020 Apr 2;16(4):858-866. doi: 10.1080/21645515.2019.1677437. Epub 2019 Nov 19. |
| Label | URL |
|---|---|
| Related info | View source |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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10 participants were randomized 1:1 to receive either QIV-HD by intramuscular (IM) route or QIV-HD by subcutaneous (SC) route (Cohort 1). After review of local and systemic AEs for 7 days post-vaccination in Cohort 1, remaining 165 participants were randomized 1:1:1 to receive QIV-HD by IM route, QIV-HD by SC route, or QIV-SD by SC route (Cohort 2)
Study participants were enrolled from 15 September 2017 to 26 October 2017 at 2 centers in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: QIV-HD by IM | Participants were randomized to receive a single 0.7-milliliter (mL) injection of high-dose Quadrivalent influenza vaccine (QIV-HD) by IM route on Day 0. |
| FG001 | Cohort 1: QIV-HD by SC | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
| FG002 | Cohort 2: QIV-HD by IM | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. |
| FG003 | Cohort 2: QIV-HD by SC | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
| FG004 | Cohort 2: QIV-SD by SC | Participants were randomized to receive a single 0.5 mL injection of standard-dose Quadrivalent influenza vaccine (QIV-SD) by SC route on Day 0. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The baseline characteristics was analyzed on SafAS which included participants who received study vaccine and analyzed according to the vaccine they actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: QIV-HD by IM | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. |
| BG001 | Cohort 1: QIV-HD by SC | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Immediate Unsolicited Adverse Events (AE) After Vaccination | An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of symptom and/or onset post-vaccination. Unsolicited AEs includes both serious and non-serious unsolicited AEs. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. | The safety analysis was performed on SafAS which included participants who received study vaccine and analyzed according to the vaccine they actually received. Data for this outcome measure was planned to be collected and analyzed for combined population of Cohort 1 and Cohort 2 participants who received QIV-HD (QIV-HD by IM and QIV-HD by SC). | Posted | Count of Participants | Participants | Within 30 minutes after vaccination |
Adverse event (AE) data was collected from Day 0 (post-vaccination) up to Day 28 after vaccination. Solicited Reaction (SR) data were collected up to Day 7 after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 28 days after vaccination).
Analyzed on SafAS. SR: an AE prelisted in CRB and considered related to vaccination. SR was therefore an adverse reaction observed and reported under conditions (symptom and onset) prelisted in CRB. An unsolicited AE: an observed AE that did not fulfill conditions prelisted in CRB in terms of symptom and/or onset post-vaccination. AE data were planned to be collected and analyzed for the combined population of Cohort 1 and Cohort 2 participants who received QIV-HD (QIV-HD by IM and QIV-HD by SC)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 and 2: QIV-HD by IM | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sudden hearing loss | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cystitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Sanofi Pasteur | 800-633-1610 | 1# | Contact-US@sanofi.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 12, 2017 | Nov 28, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 13, 2017 | Nov 28, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| D007252 | Influenza Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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Safety and tolerability was initially assessed in the first 10 participants in a smaller cohort (Cohort 1). Participants were randomized 1:1 into 2 groups in Cohort 1: QIV-HD by IM route (n=5) and QIV-HD by SC route (n=5).
After review of the local and systemic adverse events, the remaining 165 participants were enrolled (Cohort 2). Participants were randomized 1:1:1 into 3 groups in Cohort 2: QIV-HD by IM route (n=55), QIV-HD by SC route (n=55), and QIV-SD by SC route (n=55).
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QHD00008 was a modified double-blind study in which only the designated administrator at each study site knew which vaccine was administered to the participants. The participants and the Investigator/Sub-investigator in charge of the safety assessment were blinded in order to decrease the potential bias in safety assessment.
| QIV-SD by SC | Biological | SC, injected into the upper arm (posterior region) |
|
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| QIV-HD by SC | Biological | SC, injection into the upper arm (posterior region) |
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An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. |
| Up to 6 months after vaccination |
| Cohort 2: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD |
GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using an HAI assay. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination. |
| Day 0 (pre-vaccination) and Day 28 (post-vaccination) |
| Cohort 2: Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With QIV-HD or QIV-SD | Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroconversion was defined as either a HAI titer lesser than (<) 10 (1/dilution) at Day 0 and post-vaccination titer greater than or equal to (>=) 40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. | Day 28 (post-vaccination) |
| Cohort 2: Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With QIV-HD or QIV-SD | Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28. | Day 0 (pre-vaccination) and Day 28 (post-vaccination) |
| Tokyo |
| Japan |
| BG002 | Cohort 2: QIV-HD by IM | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. |
| BG003 | Cohort 2: QIV-HD by SC | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
| BG004 | Cohort 2: QIV-SD by SC | Participants were randomized to receive a single 0.5 mL injection of QIV-SD by SC route on Day 0. |
| BG005 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Cohort 1 and 2: QIV-HD by IM | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by IM route on Day 0. |
| OG001 | Cohort 1 and 2: QIV-HD by SC | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. |
| OG002 | Cohort 2: QIV-SD by SC | Participants were randomized to receive a single 0.5 mL injection of QIV-SD by SC route on Day 0. |
|
|
| Primary | Number of Participants With Solicited Injection Site and Systemic Reactions | A solicited reaction was an adverse reaction observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions: pain, erythema, swelling, induration, and bruising. Solicited systemic reactions: fever, headache, malaise, myalgia, and shivering. | The safety analysis was performed on SafAS which included participants who received study vaccine and analyzed according to the vaccine they actually received. Data for this outcome measure was planned to be collected and analyzed for combined population for Cohort 1 and Cohort 2 participants who received QIV-HD (QIV-HD by IM and QIV-HD by SC). | Posted | Count of Participants | Participants | No | Within 7 days after vaccination |
|
|
|
| Primary | Number of Participants With Unsolicited Adverse Events After Vaccination | An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | The safety analysis was performed on SafAS which included participants who received study vaccine and analyzed according to the vaccine they actually received. Data for this outcome measure was planned to be collected and analyzed for combined population of Cohort 1 and Cohort 2 participants who received QIV-HD (QIV-HD by IM and QIV-HD by SC). | Posted | Count of Participants | Participants | Within 28 days after vaccination |
|
|
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| Primary | Number of Participant With Serious Adverse Events (SAEs) After Vaccination | An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | The safety analysis was performed on SafAS which included participants who received study vaccine and analyzed according to the vaccine they actually received. Data for this outcome measure was planned to be collected and analyzed for combined population of Cohort 1 and Cohort 2 participants who received QIV-HD (QIV-HD by IM and QIV-HD by SC). | Posted | Count of Participants | Participants | Up to 6 months after vaccination |
|
|
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| Secondary | Cohort 2: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD | GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using a hemagglutination inhibition (HAI) assay. | Analyzed on PPAS which included all participants who received at least 1 dose of study vaccine, and had post-vaccination blood sample HAI result for at least 1 strain, with no protocol deviations. Here, 'number analyzed' = participants with available data for each category. Data for this outcome measure was not planned to be analyzed for Cohort 1. | Posted | Geometric Mean | 95% Confidence Interval | titers (1/dilution) | Day 0 (pre-vaccination) and Day 28 (post-vaccination) |
|
|
|
| Secondary | Cohort 2: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With QIV-HD or QIV-SD | GMT of anti-influenza antibodies strains (A1, A1-like, A2, A2-like, B1, B2, B2-like) were measured using an HAI assay. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination. | The analysis was performed on PPAS which included all participants who received at least 1 dose of study vaccine, and had post-vaccination blood sample HAI result for at least 1 strain, with no protocol deviations. Data for this outcome measure was not planned to be analyzed for Cohort 1. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Day 0 (pre-vaccination) and Day 28 (post-vaccination) |
|
|
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| Secondary | Cohort 2: Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With QIV-HD or QIV-SD | Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroconversion was defined as either a HAI titer lesser than (<) 10 (1/dilution) at Day 0 and post-vaccination titer greater than or equal to (>=) 40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. | Analyzed on PPAS which included all participants who received at least 1 dose of study vaccine, and had post-vaccination blood sample HAI result for at least 1 strain, with no protocol deviations. Here, 'number analyzed' = participants with available data for each category. Data for this outcome measure was not planned to be analyzed for Cohort 1. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 28 (post-vaccination) |
|
|
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| Secondary | Cohort 2: Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With QIV-HD or QIV-SD | Anti-influenza antibodies were measured by using the HAI assay for the strains A1, A1-like, A2, A2-like, B1, B2, and B2-like. Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28. | Analyzed on PPAS which included all participants who received at least 1 dose of study vaccine, and had post-vaccination blood sample HAI result for at least 1 strain, with no protocol deviations. Here, 'number analyzed' = participants with available data for each category. Data for this outcome measure was not planned to be analyzed for Cohort 1. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 0 (pre-vaccination) and Day 28 (post-vaccination) |
|
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|
| 0 |
| 60 |
| 0 |
| 60 |
| 4 |
| 60 |
| EG001 | Cohort 1 and 2: QIV-HD by SC | Participants were randomized to receive a single 0.7 mL injection of QIV-HD by SC route on Day 0. | 0 | 60 | 0 | 60 | 4 | 60 |
| EG002 | Cohort 2: QIV-SD by SC | Participants were randomized to receive a single 0.5 mL injection of QIV-SD by SC route on Day 0. | 0 | 55 | 1 | 55 | 7 | 55 |
| Laryngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Faeces soft | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Injection site pruritus | General disorders | MedDRA 20.1 | Systematic Assessment |
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The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
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| Injection site swelling |
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| Injection site induration |
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| Injection site bruising |
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| Fever |
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| Headache |
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| Malaise |
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| Myalgia |
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| Shivering |
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| A1-like: Day 0 |
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| A2: Day 0 |
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| A2-like: Day 0 |
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| B1: Day 0 |
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| B2: Day 0 |
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| B2-like: Day 0 |
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| A1: Day 28 |
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| A1-like: Day 28 |
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| A2: Day 28 |
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| A2-like: Day 28 |
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| B1: Day 28 |
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| B2: Day 28 |
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| B2-like: Day 28 |
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| A2: Day 28/Day 0 |
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| A2-like: Day 28/Day 0 |
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| B1: Day 28/Day 0 |
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| B2: Day 28/Day 0 |
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| B2-like: Day 28/Day 0 |
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| A2 |
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| B1 |
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| A1-like: Day 0 |
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| A2: Day 0 |
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| A2-like: Day 0 |
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| B1: Day 0 |
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| B2: Day 0 |
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| B2-like: Day 0 |
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| A1: Day 28 |
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| A1-like: Day 28 |
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| A2: Day 28 |
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| A2-like: day 28 |
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| B1: Day 28 |
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| B2: Day 28 |
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| B2-like: Day 28 |
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