Vaccine-Preventable DiseasesPhase 3NCT06088745
A Phase Ⅲ Clinical Study to Evaluate Protective Efficacy and Safety of a Recombinant Herpes Zoster Vaccine
A Phase 3 study testing Recombinant Herpes Zoster Vaccine in people with Vaccine-Preventable Diseases and Herpes Zoster, run by Beijing Luzhu Biotechnology Co., Ltd. at 1 site in China.
Trial summary
This clinical trial is to study protective efficacy and safety of a recombinant herpes zoster vaccine (LZ901) and sponsored by Beijing Luzhu Biotechnology Co., Ltd. It is a phase Ⅲ, randomized, double-blind, placebo-controlled in healthy people aged 40 years and older. Read more about this study
- Who is it for?
- Ages 40 years and olderHealthy volunteers can take part
- Conditions the study is for
- Vaccine-Preventable Diseases, Herpes Zoster
- What is being tested?
- Recombinant Herpes Zoster Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteChina
- Study dates
- 28 Sep 2023to 31 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and females able to provide legal identity certificate, aged ≥ 40 years inclusive at the time of signing the ICF;
- Able to understand the study procedures, voluntarily agree to participate in the study, and sign the ICF;
- Female subjects are not pregnant or lactating. Female subjects with childbearing potential should take reliable contraceptive measures, and have no pregnancy and fertility plan within 7 months;
- Axillary temperature ≤ 37.0℃ on the day of enrollment;
- Able to attend all scheduled follow-up visits and able to comply with protocol requirements;
Who cannot join
- Subjects who have had herpes zoster within the previous 5 years;
- Previous vaccination against varicella or shingles (including use of a registered product or participation in a clinical trial of varicella or shingles vaccine);
- Hypersensitivity to any of the components of the test vaccine: or prior hypersensitivity to any recombinant vaccine of CHO cell origin [e.g., recombinant hepatitis B vaccine (CHO cell)], polysorbate, etc.; or prior history of severe allergy* to any of the vaccinations;
- Severe allergies: anaphylaxis, anaphylactic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, localized anaphylactic necrotic reaction (Arthus reaction), severe urticaria.
- Developed immunodeficiency diseases (congenital or acquired immunodeficiency diseases, human immunodeficiency virus infection) or received immunosuppressive/cytotoxic treatments (cancer chemotherapy, organ transplantation, or treatment planned during a clinical trial in the 6 months prior to vaccination);
- Receiving immunosuppressive therapy (e.g., long-term systemic glucocorticoid application for ≥14 days at a dose of ≥2 mg/kg/day or ≥20 mg/day of prednisone or prednisone-equivalent dose) within 3 months prior to vaccination or within 1 month after the planned full course of immunization；
Show all 12Show fewer
- Received an inactivated or recombinant vaccine or mRNA vaccine within 14 days or any live attenuated vaccine within 28 days prior to vaccination;
- Subjects who are suffering from an acute illness or are in the acute exacerbation phase of a chronic disease within 3 days prior to vaccination;
- History of asplenia or functional asplenia, and asplenia or splenectomy due to any condition;
- Treatment with blood products or globulins within 3 months prior to enrollment, or planned use of such products within 2 months of vaccination;
- Participating in other clinical studies of investigational or un-registered products (drugs, vaccines or devices, etc.), or planning to participate in other clinical studies before the end of this clinical study;
- Significant underlying medical conditions that, in the opinion of the investigator, may prevent completion of the trial (e.g., life-threatening disease that may limit survival to less than 4 years) or any other condition
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Jiangsu Province Center for Disease Control and Prevention (China)
Zhenjiang, Jiangsu, 210009
Fengcai Zhu, MM, 13951994867, jscdczfc@126.com
Pengfei Jin, 18852048896, kingpfph@sina.com
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety, and Immunogenicity of Recombinant Herpes Zoster Vaccine (CHO Cells) in Subjects Aged 40 Years and Older
This clinical trial is to study protective efficacy and safety of a recombinant herpes zoster vaccine (LZ901) and sponsored by Beijing Luzhu Biotechnology Co., Ltd. It is a phase Ⅲ, randomized, double-blind, placebo-controlled in healthy people aged 40 years and older. The study is to protect adults against shingles (herpes zoster / varicella zoster virus(VZV)). There will be about 26000 participators who will receive two-dose injection at the upper arm.
LZ901 vaccine is made up of a tetramer of VZV glycoprotein E (VZV gE-Fc) and adsorbed with aluminum hydroxide adjuvant. This adjuvant can raise the immune response to a lot of antigens. It is the most widely used and safe adjuvant in various types of vaccines worldwide.
Read the detailed description
In this study:
- The participation is voluntary.
- Before the trial, participants will receive some tests for screening. If qualified, investigators will officially invite them to join this trial.
- The trial vaccine is LZ901 (100μg/0.5 mL). The placebo, which is aluminum hydroxide adjuvant, has no active drug. Participants will receive one of two as above mentioned.
- This trial included a protective efficacy test and a batch-to-batch consistency test (immunization subgroup). Approximately 26000 subjects aged 40 years and older will be enrolled. Subjects will be randomized to receive either LZ901 or placebo in which about 3000 subjects will be enrolled into immunization subgroup and randomly receive three different batches LZ901 and one batch placebo at a ratio of 1:1:1:3. The immunization subgroup was designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 12, 24, and 36 months after full immunization.
- All subjects will receive the LZ901 or Placebo on day 0 and day 29. Subject will have 16 visits, including 5 on-site visits and 11 in-person visits except for subjects in the immunization subgroup who have 24 visits, including 8 on-site visits and 16 in-line visits.
- The primary objective was to evaluate the Vaccine Efficacy (VE) of LZ901 against herpes zoster, as compared with placebo, after 30 days of full immunization in people 40 years of age and older.
- The secondary objective was to evaluate the protective efficacy of LZ901, as compared with placebo, against laboratory-confirmed cases of HZ after 30 days of full vaccination in people 40 years of age and older. To evaluate the safety of LZ901. The immunogenicity of LZ901was evaluated (immunization subgroup). To evaluate the batch-to-batch consistency of immunogenicity of three batches of LZ901 in subject aged ≥40 years (immunization subgroup).
- An exploratory objective was to evaluate the effect of LZ901 on reducing the severity of PHN in HZ subjects ≥40 years old." To evaluate the efficacy of LZ901 compared with placebo in preventing PHN in subjects ≥40 years old with HZ efficacy endpoint. The immunogenicity of LZ901 was evaluated at 12, 24 and 36 months after full immunization in subject ≥40 years old (immunization subgroup).
- Conditions
- Vaccine-Preventable Diseases, Herpes Zoster
- Being tested
- Recombinant Herpes Zoster Vaccine, Recombinant Herpes Zoster Vaccine Placebo
- Medical subject headings
- Vaccine-Preventable Diseases, Herpes Zoster
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Herpes Zoster VaccineBiological
Also called LZ901
The active ingredient of the recombinant herpes zoster vaccine is varicella-zoster virus glycoprotein E fusion protein expressed in CHO cells by gene recombination technology. The LZ901 cell line carrying this gene is cultured in chemically defined medium. The harvest cell culture is purified by multi-step liquid chromatography. After Low pH incubation and virus removal filter package Nanofiltration inactivation/virus removal process, the bulk containing high-purity recombinant herpes zoster virus glycoprotein E is obtained. Finally, an alumina adjuvant is added to the formulated final product.
Recombinant Herpes Zoster Vaccine PlaceboBiological
Alumina adjuvant
| Study group | Role | What they receive |
|---|---|---|
| Treatment main group | Experimental | 11500 subjects in treatment main group will receive 2 doses of LZ901 at D0 and D29. This group will be required to complete a 12 month safety follow-up after full immunization. Receives: Biological: Recombinant Herpes Zoster Vaccine |
| Placebo main group | Placebo comparator | 11500 subjects in placebo main group will receive 2 doses of placebo at D0 and D29. This group will be required to complete a 12 month safety follow-up after full immunization. Receives: Biological: Recombinant Herpes Zoster Vaccine Placebo |
| Treatment immunization group | Experimental | 1500 subjects in treatment immunization group will receive 2 doses of LZ901 at D0 and D29. This group is designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 36 months after full immunization. Receives: Biological: Recombinant Herpes Zoster Vaccine |
| Placebo immunization group | Placebo comparator | 1500 subjects in placebo immunization group will receive 2 doses of placebo at D0 and D29. This group is designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 36 months after full immunization. Receives: Biological: Recombinant Herpes Zoster Vaccine Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Vaccine Efficacy
To evaluate the Vaccine Efficacy in the prevention of HZ compared to placebo based on the number of confirmed cases of HZ
Measured: 30 days after full immunization
Secondary outcomes (8)
Solicited AE
Incidence of Solicited AE include site of vaccination (local) and non-site of vaccination (systemic)
Measured: from 0 to 7 days after each dose
Unsolicited AE
Incidence of unsolicited AEs, include all AEs, except solicited AEs reported Days 0~6 after the study intervention.
Measured: From 0 to 30 days after each dose
AE
Incidence of AE refers to any untoward medical occurrence in a subject administered the investigational vaccine.
Measured: Within 30 minutes after each dose
Adverse Events of Special Interest
Confirmed cases of HZ within 30 days after the first dose and full immunization
Measured: From initial dose to 30 days after full immunization
Serious Adverse Event
The incidence of all serious adverse events (SAEs)
Measured: From first dose to 12 months after full immunization
Anti-GE antibody
Seroconversion rate of anti-GE antibody in three different batches of immunization groups
Measured: 30 days after full immunization
Geometric Mean Fold Increase
Geometric Mean Fold Increase (GMFI) of anti-GE antibody in three different batches of immunization groups compared with pre-vaccination (day 0)
Measured: 30 days after full immunization
GMC ratios
GMC ratios of anti-GE antibodies in three different batches of immunization groups
Measured: 30 days after full immunization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2023
- Study start28 Sep 2023
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vaccine-Preventable DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Luzhu Biotechnology Co., Ltd.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fengcai Zhu, MM, Principal investigator, Jiangsu Province Center for Disease Control and Prevention (China)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06088745
- Sponsor's protocol ID
- LZ901-300
- Status last verified
- Oct 2023
- First submitted
- 26 Sep 2023
- Last updated
- 18 Oct 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety, and Immunogenicity of Recombinant Herpes Zoster Vaccine (CHO Cells) in Subjects Aged 40 Years and Older
- ClinicalTrials.gov ID
- NCT06088745
- Acronym / sponsor ID
- LZ901-300
- Conditions
- Vaccine-Preventable Diseases, Herpes Zoster
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 4 participants (estimated)
- Lead sponsor
- Beijing Luzhu Biotechnology Co., Ltd.University, hospital or other
- Study start
- 28 Sep 2023 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is to study protective efficacy and safety of a recombinant herpes zoster vaccine (LZ901) and sponsored by Beijing Luzhu Biotechnology Co., Ltd. It is a phase Ⅲ, randomized, double-blind, placebo-controlled in healthy people aged 40 years and older. The study is to protect adults against shingles (herpes zoster / varicella zoster virus(VZV)). There will be about 26000 participators who will receive two-dose injection at the upper arm.
LZ901 vaccine is made up of a tetramer of VZV glycoprotein E (VZV gE-Fc) and adsorbed with aluminum hydroxide adjuvant. This adjuvant can raise the immune response to a lot of antigens. It is the most widely used and safe adjuvant in various types of vaccines worldwide.
Detailed description
In this study:
- The participation is voluntary.
- Before the trial, participants will receive some tests for screening. If qualified, investigators will officially invite them to join this trial.
- The trial vaccine is LZ901 (100μg/0.5 mL). The placebo, which is aluminum hydroxide adjuvant, has no active drug. Participants will receive one of two as above mentioned.
- This trial included a protective efficacy test and a batch-to-batch consistency test (immunization subgroup). Approximately 26000 subjects aged 40 years and older will be enrolled. Subjects will be randomized to receive either LZ901 or placebo in which about 3000 subjects will be enrolled into immunization subgroup and randomly receive three different batches LZ901 and one batch placebo at a ratio of 1:1:1:3. The immunization subgroup was designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 12, 24, and 36 months after full immunization.
- All subjects will receive the LZ901 or Placebo on day 0 and day 29. Subject will have 16 visits, including 5 on-site visits and 11 in-person visits except for subjects in the immunization subgroup who have 24 visits, including 8 on-site visits and 16 in-line visits.
- The primary objective was to evaluate the Vaccine Efficacy (VE) of LZ901 against herpes zoster, as compared with placebo, after 30 days of full immunization in people 40 years of age and older.
- The secondary objective was to evaluate the protective efficacy of LZ901, as compared with placebo, against laboratory-confirmed cases of HZ after 30 days of full vaccination in people 40 years of age and older. To evaluate the safety of LZ901. The immunogenicity of LZ901was evaluated (immunization subgroup). To evaluate the batch-to-batch consistency of immunogenicity of three batches of LZ901 in subject aged ≥40 years (immunization subgroup).
- An exploratory objective was to evaluate the effect of LZ901 on reducing the severity of PHN in HZ subjects ≥40 years old." To evaluate the efficacy of LZ901 compared with placebo in preventing PHN in subjects ≥40 years old with HZ efficacy endpoint. The immunogenicity of LZ901 was evaluated at 12, 24 and 36 months after full immunization in subject ≥40 years old (immunization subgroup).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment main group | Experimental | Biological: Recombinant Herpes Zoster Vaccine11500 subjects in treatment main group will receive 2 doses of LZ901 at D0 and D29. This group will be required to complete a 12 month safety follow-up after full immunization. |
| Placebo main group | Placebo comparator | Biological: Recombinant Herpes Zoster Vaccine Placebo11500 subjects in placebo main group will receive 2 doses of placebo at D0 and D29. This group will be required to complete a 12 month safety follow-up after full immunization. |
| Treatment immunization group | Experimental | Biological: Recombinant Herpes Zoster Vaccine1500 subjects in treatment immunization group will receive 2 doses of LZ901 at D0 and D29. This group is designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 36 months after full immunization. |
| Placebo immunization group | Placebo comparator | Biological: Recombinant Herpes Zoster Vaccine Placebo1500 subjects in placebo immunization group will receive 2 doses of placebo at D0 and D29. This group is designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 36 months after full immunization. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males and females able to provide legal identity certificate, aged ≥ 40 years inclusive at the time of signing the ICF;
- Able to understand the study procedures, voluntarily agree to participate in the study, and sign the ICF;
- Female subjects are not pregnant or lactating. Female subjects with childbearing potential should take reliable contraceptive measures, and have no pregnancy and fertility plan within 7 months;
- Axillary temperature ≤ 37.0℃ on the day of enrollment;
- Able to attend all scheduled follow-up visits and able to comply with protocol requirements;
Key exclusion criteria (12 listed)
- Subjects who have had herpes zoster within the previous 5 years;
- Previous vaccination against varicella or shingles (including use of a registered product or participation in a clinical trial of varicella or shingles vaccine);
- Hypersensitivity to any of the components of the test vaccine: or prior hypersensitivity to any recombinant vaccine of CHO cell origin [e.g., recombinant hepatitis B vaccine (CHO cell)], polysorbate, etc.; or prior history of severe allergy* to any of the vaccinations;
- Severe allergies: anaphylaxis, anaphylactic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, localized anaphylactic necrotic reaction (Arthus reaction), severe urticaria.
- Developed immunodeficiency diseases (congenital or acquired immunodeficiency diseases, human immunodeficiency virus infection) or received immunosuppressive/cytotoxic treatments (cancer chemotherapy, organ transplantation, or treatment planned during a clinical trial in the 6 months prior to vaccination);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant Herpes Zoster VaccineAlso: LZ901The active ingredient of the recombinant herpes zoster vaccine is varicella-zoster virus glycoprotein E fusion protein expressed in CHO cells by gene recombination technology. The LZ901 cell line carrying this gene is cultured in chemically defined medium. The harvest cell culture is purified by multi-step liquid chromatography. After Low pH incubation and virus removal filter package Nanofiltration inactivation/virus removal process, the bulk containing high-purity recombinant herpes zoster virus glycoprotein E is obtained. Finally, an alumina adjuvant is added to the formulated final product. | Biological | Treatment immunization group, Treatment main group |
| Recombinant Herpes Zoster Vaccine PlaceboAlumina adjuvant | Biological | Placebo immunization group, Placebo main group |
Primary outcome
The Vaccine Efficacy
Time frame: 30 days after full immunization
To evaluate the Vaccine Efficacy in the prevention of HZ compared to placebo based on the number of confirmed cases of HZ
8 secondary outcomes
Solicited AE
Time frame: from 0 to 7 days after each dose
Unsolicited AE
Time frame: From 0 to 30 days after each dose
AE
Time frame: Within 30 minutes after each dose
Adverse Events of Special Interest
Time frame: From initial dose to 30 days after full immunization
Serious Adverse Event
Time frame: From first dose to 12 months after full immunization
Anti-GE antibody
Time frame: 30 days after full immunization
Geometric Mean Fold Increase
Time frame: 30 days after full immunization
GMC ratios
Time frame: 30 days after full immunization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2023.
- Individual participant dataSharing planned: No
Related trials for Vaccine-Preventable Diseases
Recruiting
The Immune Responses After Hepatitis B Revaccination Doses in a Young Cohort
Hepatitis B, Vaccination; Infection
Not yet recruitingPhase 4
Single-center, Open-label Study: Immunogenicity and Safety Observation After Vaccination With ACYW135 Meningococcal Polysaccharide Vaccine in Junior High School Students Aged 13-15 Years
Meningococcal Disease; Meningococcal Meningitis
Active, not recruitingPhase 1/2
Safety and Immunogenicity of an Investigational Herpes Zoster Vaccine (Z-1018) Compared to Shingrix® in Healthy Adults 50 Years of Age and Over
Shingles, Herpes Zoster
RecruitingPhase 4
Adding Male Single Dose HPV Vaccination to Female HPV Vaccination in Tanzania
HPV Infection, Vaccine Preventable Disease
Active, not recruitingObservational study
Herpes Virus Infections in Kidney Transplant Patients
Kidney Transplant; Complications, Varicella Zoster Virus Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fengcai Zhu, MM principal investigator
Jiangsu Province Center for Disease Control and Prevention (China)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Recombinant Herpes Zoster Vaccine in people with Vaccine-Preventable Diseases and Herpes Zoster, run by Beijing Luzhu Biotechnology Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fengcai Zhu, MM (13951994867, jscdczfc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Vaccine Efficacy (time frame: 30 days after full immunization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2023.