Coronavirus Disease 2019Phase 2NCT04343651
Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate COVID-19
A Phase 2 study testing Leronlimab (700mg) in people with Coronavirus Disease 2019, run by CytoDyn, Inc. at 12 sites in United States.
Trial summary
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Coronavirus Disease 2019
- What is being tested?
- Leronlimab (700mg)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 12 sitesUnited States
- Study dates
- 1 Apr 2020to 20 Sep 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female adult ≥ 18 years of age at time of enrollment.
- Subjects with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection as defined below:
- Mild (uncomplicated) Illness:
- Diagnosed with COVID-19 by a standardized RT-PCR assay AND
- Mild symptoms, such as fever, rhinorrhea, mild cough, sore throat, malaise, headache, muscle pain, or malaise, but with no shortness of breath AND
- No signs of a more serious lower airway disease AND
Show all 16Show fewer
- RR<20, HR <90, oxygen saturation (pulse oximetry) > 93% on room air
- Moderate Illness:
- Diagnosed with COVID-19 by a standardized RT-PCR assay AND
- In addition to symptoms above, more significant lower respiratory symptoms, including shortness of breath (at rest or with exertion) OR
- Signs of moderate pneumonia, including RR ≥ 20 but <30, HR ≥ 90 but less than 125, oxygen saturation (pulse oximetry) > 93% on room air AND
- If available, lung infiltrates based on X-ray or CT scan < 50% present
- Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
- Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
- Understands and agrees to comply with planned study procedures.
- Women of childbearing potential must agree to use at least one medically accepted method of contraception (e.g., barrier contraceptives [condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or intrauterine devices) for the duration of the study.
Who cannot join
- Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening;
- History of severe chronic respiratory disease and requirement for long-term oxygen therapy;
- Subjects showing signs of clinical jaundice at the time of screening;
- History of moderate and severe liver disease (Child-Pugh score >12);
- Subjects requiring Renal Replacement Therapy (RRT) at the time of screening;
- History of severe chronic kidney disease or requiring dialysis;
Show all 13Show fewer
- Any uncontrolled active systemic infection requiring admission to an intensive care unit (ICU); Note: Subjects infected with chronic hepatitis B virus or hepatitis C virus will be eligible for the study if they have no signs of hepatic decompensation.
- Note: Subjects infected with HIV-1 will be eligible for the study with undetectable viral load and are on a stable ART regimen. Investigators are required to review the subjects' medical records to confirm HIV-1 RNA suppression within the previous 3 months.
- Note: Empirical antibiotic treatment for secondary bacterial infections is allowed during the course of study.
- Patients with malignant tumor, or other serious systemic diseases;
- Patients who are participating in other clinical trials;
- Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to leronlimab (PRO 140) are not eligible; and
- Inability to provide informed consent or to comply with test requirements
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Novant Health
Charlotte, North Carolina, 27103
Ohio Health
Columbus, Ohio, 43215
Center for Advanced Research & Education (CARE)
Gainesville, Georgia, 30501
University of California, Los Angeles
Los Angeles, California, 90095
Atlantic Health System Hospital
Morristown, New Jersey, 07962-1905
Yale
New Haven, Connecticut, 06510
Palmtree Clinical Research, Inc.
Palm Springs, California, 92262-4871
Oregon Health and Science University
Portland, Oregon, 97239
Eisenhower Health
Rancho Mirage, California, 92270
Montefiore Medical Center
The Bronx, New York, 10467
White Plains Hospital
White Plains, New York, 10601
About this study
Official title: A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.
Read the detailed description
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.
The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period.
A total of 75 subjects will be randomized 2:1 in this study.
- Conditions
- Coronavirus Disease 2019
- Being tested
- Placebo, Leronlimab (700mg)
- Keywords
- COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo
Leronlimab (700mg)Drug
Also called PRO 140
Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | The placebo comparator consists of the formulation buffer for leronlimab, i.e., the placebo is the same as the active arm without leronimab. The placebo is presented in the same container closure at the same fill volume as the active (nominal 1mL fill volume). The formulation buffer contains histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections. Receives: Drug: Placebo |
| 700mg Leronlimab | Experimental | Each vial of active contains 175mg of leronlimab at a concentration of 175mg/ml (nominal 1mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections. Receives: Drug: Leronlimab (700mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Total Symptom Score
Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) by count of patients showing improvement, no change or worsened.
Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. Higher scores mean a worse outcome. A negative change from baseline shows an improvement in symptom score.
Measured: Clinical Improvement will be assessed at baseline and at EOT (day 14).
Secondary outcomes (12)
Time to Clinical Resolution (TTCR)
Defined as the time from initiation of study treatment to the resolution of clinical symptoms (fever, myalgia, dyspnea, cough).
Data presented how the number of days at which a certain percentage of patients achieve resolution of symptoms, i.e., 50% of patients on placebo saw resolution of symptoms in 15 days, and 15 days for patients on leronlimab.
The hazard ratio was 0.781, 95% Confidence Interval 0.43, 1.41 and the p-value was 0.4138.
TTCR is defined as the duration from date of first exposure to treatment to the first occurrence of total symptom score equals 0.
Measured: Time (in days) from initiation of study treatment until resolution of clinical symptoms (fever, myalgia, dyspnea and cough).
Incidence of Hospitalization
Number of patients requiring hospitalization
Measured: From visit 2 (day 0) through day 14 (in days)
Duration (Days) of Hospitalization
Duration of hospitalization in days
Measured: Total duration of hospitalization between visit 2 (day 0) in days and end of treatment
Incidence of Mechanical Ventilation
Incidence of mechanical ventilation supply
Measured: Total duration of mechanical ventilation since visit 2 (day 0) (days)
Duration of Mechanical Ventilation Supply
Duration (days) of mechanical ventilation supply
Measured: Duration of mechanical ventilation since visit 2 (day 0) (days
Incidence of Oxygen Use
Incidence of oxygen use over course of treatment
Measured: Use of oxygen since visit 2 (day 0) to end of treatment
Duration of Oxygen Use
Duration of oxygen use in days
Measured: Total duration of oxygen use since visit 2 (day 0) to EOT (day 14) (days)
Mortality at Day 14
Incidence of mortality at day 14
Measured: Mortality at EOT (day 14)
Time to Return to Normal Activity
Time to return to normal activity from initiation of study treatment defined as duration from date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities"
Measured: Date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities"
Change From Baseline in National Early Warning Score 2 (NEWS2) to Day 3, 7 and 14
NEWS2 is an assessment based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness) developed by the Royal College of Physicians (https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2). Respiratory rate (bpm) scores 0-3; Sp02 (on room air or suppl) scores 0-3; SpO2 (hypercapnic resp failure) scores 0-3; room air or supplemental O2 scores 0 (room) or 2 (suppl); temperature - scores 0-3; systolic BP scores 0-3; pulse (bpm) scores 0-3; consciousness - alert (score 0) vs. new onset confusion (score 3). The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention and more intensive monitoring.
Change shown is positive or negative from baseline, with a negative number indicating improvement (i.e., a decrease in total score).
Measured: Baseline to Day 3, 7 and 14
Mean Change in Percent Oxygen Saturation From Baseline to Days 3, 7 and 14
Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14 for patients with paired values
Measured: Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14
Change From Baseline in the Patient's Health Status on a 7-category Ordinal Scale on Days 3, 7 and 14
A 7-category ordinal scale of patient health status ranges from: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Lower scores mean a worse outcome.
Measured: Assessments performed Day 0 (first treatment is Visit 2, day 0), Visit 3 (3+/- 1 day after first treatment) Visit 4 (second treatment, 7+/- 1 day from V2, day7) and end of treatment (7+/- 1 day from V4, day 14)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2020
- Study start1 Apr 2020
- Primary completion21 Jul 2020
- Study completion20 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronavirus Disease 2019Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- CytoDyn, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Angela Ritter, MD, Principal investigator, Center for Advanced Research and Education
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04343651
- Sponsor's protocol ID
- CD10_COVID-19
- Status last verified
- Dec 2022
- First submitted
- 31 Mar 2020
- Last updated
- 4 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Seethamraju H, Yang OO, Loftus R, Ogbuagu O, Sammartino D, Mansour A, Sacha JB, Ojha S, Hansen SG, Arman AC, Lalezari JP. A Randomized Placebo-Controlled Trial of Leronlimab in Mild-To-Moderate COVID-19. Clin Ther. 2024 Nov;46(11):891-899. doi: 10.1016/j.clinthera.2024.08.019. Epub 2024 Sep 30.
PubMed 39353749
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)
- ClinicalTrials.gov ID
- NCT04343651
- Acronym / sponsor ID
- CD10_COVID-19
- Conditions
- Coronavirus Disease 2019
- Keywords
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- CytoDyn, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 21 Jul 2020 (actual)
- Study completion
- 20 Sep 2021 (actual)
- First posted
- 13 Apr 2020 (actual)
- Results
- Posted 4 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.
Detailed description
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection. Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection.
The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period.
A total of 75 subjects will be randomized 2:1 in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboThe placebo comparator consists of the formulation buffer for leronlimab, i.e., the placebo is the same as the active arm without leronimab. The placebo is presented in the same container closure at the same fill volume as the active (nominal 1mL fill volume). The formulation buffer contains histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections. |
| 700mg Leronlimab | Experimental | Drug: Leronlimab (700mg)Each vial of active contains 175mg of leronlimab at a concentration of 175mg/ml (nominal 1mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male or female adult ≥ 18 years of age at time of enrollment.
- Subjects with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection as defined below:
- Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
- Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
- Understands and agrees to comply with planned study procedures.
Key exclusion criteria (13 listed)
- Subjects showing signs of acute respiratory distress syndrome (ARDS) or respiratory failure necessitating mechanical ventilation at the time of screening;
- History of severe chronic respiratory disease and requirement for long-term oxygen therapy;
- Subjects showing signs of clinical jaundice at the time of screening;
- History of moderate and severe liver disease (Child-Pugh score >12);
- Subjects requiring Renal Replacement Therapy (RRT) at the time of screening;
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 |
|---|---|---|
| PlaceboPlacebo | Drug | Placebo |
| Leronlimab (700mg)Also: PRO 140Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5) | Drug | 700mg Leronlimab |
Primary outcome
Mean Change From Baseline in Total Symptom Score
Time frame: Clinical Improvement will be assessed at baseline and at EOT (day 14).
Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) by count of patients showing improvement, no change or worsened. Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. Higher scores mean a worse outcome. A negative change from baseline shows an improvement in symptom score.
12 secondary outcomes
Time to Clinical Resolution (TTCR)
Time frame: Time (in days) from initiation of study treatment until resolution of clinical symptoms (fever, myalgia, dyspnea and cough).
Incidence of Hospitalization
Time frame: From visit 2 (day 0) through day 14 (in days)
Duration (Days) of Hospitalization
Time frame: Total duration of hospitalization between visit 2 (day 0) in days and end of treatment
Incidence of Mechanical Ventilation
Time frame: Total duration of mechanical ventilation since visit 2 (day 0) (days)
Duration of Mechanical Ventilation Supply
Time frame: Duration of mechanical ventilation since visit 2 (day 0) (days
Incidence of Oxygen Use
Time frame: Use of oxygen since visit 2 (day 0) to end of treatment
Duration of Oxygen Use
Time frame: Total duration of oxygen use since visit 2 (day 0) to EOT (day 14) (days)
Mortality at Day 14
Time frame: Mortality at EOT (day 14)
Time to Return to Normal Activity
Time frame: Date of first exposure to treatment to the first occurrence of ordinal scale equals "not hospitalized, no limitations of activities"
Change From Baseline in National Early Warning Score 2 (NEWS2) to Day 3, 7 and 14
Time frame: Baseline to Day 3, 7 and 14
Mean Change in Percent Oxygen Saturation From Baseline to Days 3, 7 and 14
Time frame: Mean change in percent oxygen saturation from baseline to Days 3, 7 and 14
Change From Baseline in the Patient's Health Status on a 7-category Ordinal Scale on Days 3, 7 and 14
Time frame: Assessments performed Day 0 (first treatment is Visit 2, day 0), Visit 3 (3+/- 1 day after first treatment) Visit 4 (second treatment, 7+/- 1 day from V2, day7) and end of treatment (7+/- 1 day from V4, day 14)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39353749Seethamraju H, Yang OO, Loftus R, Ogbuagu O, Sammartino D, Mansour A, Sacha JB, Ojha S, Hansen SG, Arman AC, Lalezari JP. A Randomized Placebo-Controlled Trial of Leronlimab in Mild-To-Moderate COVID-19. Clin Ther. 2024 Nov;46(11):891-899. doi: 10.1016/j.clinthera.2024.08.019. Epub 2024 Sep 30.
- Individual participant dataSharing planned: No
Related trials for Coronavirus Disease 2019
RecruitingObservational study
Physiological Finding in Management of COVID 19 Patients
COVID-19 (Coronavirus Disease 2019)
Active, not recruitingObservational study
A Study to Look at the Health Outcomes of Patients With COVID-19 and Influenza
COVID-19, Coronavirus Disease 2019
RecruitingObservational study
Cardiac Magnetic Resonance Tissue Characterization in COVID-19 Survivors
COVID-19 Pneumonia, COVID-19
Active, not recruitingObservational study
A Study to Learn About How Well Yearly Updates to the COVID-19 Vaccine Work to Protect People From COVID-19 and How Much Money People Spend on Healthcare for COVID-19
COVID-19 SARS-CoV-2 Infection, COVID-19
Active, not recruiting
Thrombohemorrhagic Complications of COVID-19
COVID-19 (Coronavirus Disease 2019)
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. This study is not recruiting at the moment.
Angela Ritter, MD principal investigator
Center for Advanced Research and Education
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leronlimab (700mg) in people with Coronavirus Disease 2019, run by CytoDyn, Inc. at 12 sites in United States.
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 16 inclusion and 13 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: finished, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change From Baseline in Total Symptom Score (time frame: Clinical Improvement will be assessed at baseline and at EOT (day 14).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04343651, which also lists 1 linked publication.
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 4 Jan 2023; AzTrials last refreshed its copy on 7 Nov 2026.