Hepatitis B Virus (HBV) Viral Suppression by Entecavir in Adefovir Partial Responders

An observational study of Hepatitis B, run by Pacific Health Foundation at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 48 weeks of entecavir following partial response to adefovir. The aim of the study is to describe sequential virologic response to adefovir and entecavir. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hepatitis B
What is being tested?: Entecavir
How many people: 60 participants
Where: 6 sitesUnited States
Study dates: May 2008to Oct 2011
Phase: Observational
Are there results?: None posted in the registry

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: * Age 18 years or older * All genders and ethnicity * Positive HBsAg * HBeAg positive and negative * Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed) * Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician * Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

Who may be able to join

Age 18 years or older
All genders and ethnicity
Positive HBsAg
HBeAg positive and negative
Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed)
Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician.
Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

Who cannot join

Patients who refused to consent to the study
Patients younger than 18
Vulnerable subjects such as pregnant women, prisoners, employees, patients with significant cognitive deficits.
Patients with prior exposure to another nucleoside for more than 2 weeks. Those with prior exposure to lamivudine will be enrolled under conditions detailed above.
HIV co-infection
HCV co-infection

Show all 9Show fewer

HDV co-infection
Recipients of solid organ transplantation
Patients who receive high-dose steroid (60 mg/d or higher and for longer than 10 days)

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Asian Village Medical Clinic
Chicago, Illinois, 60640
Houston Gastroenterology Clinic
Houston, Texas, 77072
Stanford University Medical Center
Palo Alto, California, 94304
Digestive Health Associates of Texas
Plano, Texas, 75093
San Jose Gastroenterology
San Jose, California, 95116
San Jose Gastroenterology
San Jose, California, 95128

Other trials in United States

About this study

Official title: HBV Viral Suppression by Entecavir in Adefovir Partial Responders

Read the detailed description

Amendment was made, and approved by WIRB in January 2009, to this protocol: We propose a largely retrospective study with short-term prospective follow-up in a subgroup of patients who have not yet been treated with 96 weeks of entecavir following adefovir treatment. The aim of the study is to describe sequential virologic response to adefovir and entecavir.

Conditions: Hepatitis B
Being tested: Entecavir
Keywords: Hepatitis B, HBV, Treatment
Medical subject headings: Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EntecavirDrug
Also called Baraclude
0.5 or 1 mg dose qd

Study groups in NCT00704106
Study group	Role	What they receive
Group 1		Persistent viremia after 48 weeks or longer. Receives: Drug: Entecavir
Group 2		<2 log IU/mL drop from initial HBVDNA after 12 weeks of adefovir Receives: Drug: Entecavir
Group 3		Patients who responded to adefovir and were switched to entecavir. Receives: Drug: Entecavir
Group 4		Patients with 160 copies/mL (100 IU/mL) or higher at the time of medication switch. Receives: Drug: Entecavir

What is being measured

The primary outcome is the main question the study is designed to answer.

HBV DNA PCR after 12 weeks of entecavir from the time of medication switching: percent of patients with <2log drop in HBV DNA and percent of patients with complete viral suppression during adefovir versus during entecavir.
Measured: 48 weeks or after

Secondary outcomes (4)

HBV DNA PCR after 24 weeks of entecavir from the time of medication switching.
Measured: 48 weeks or after
HBV DNA PCR after 48 weeks of entecavir from the time of medication switching.
Measured: 48 weeks or after
BR and CR at 24 and 48 weeks of therapy with entecavir.
Measured: 48 weeks or after.
BR and CR for longer duration of therapy if available.
Measured: 48 weeks or after.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Oct 2011

First posted24 Jun 2008 (estimated)
Study startMay 2008
Primary completionOct 2011
Study completionOct 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (15)Papers the sponsor has linked to this study.
Other trials for Hepatitis BStudies 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: Observational
Observational model: Cohort
Time perspective: Other
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00704106
Sponsor's protocol ID: PHF008
Acronym: ADVPR
Status last verified: Nov 2022
First submitted: 20 Jun 2008
Last updated: 14 Nov 2022
Results posted: No
Data monitoring committee: No

Publications

McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25 Suppl 1:3-8. doi: 10.1055/s-2005-915644.
PubMed 16103976
Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
PubMed 16391218
Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.
PubMed 16530509
Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
PubMed 15470215
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available.
PubMed 17256718
Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. 2006 Aug;4(8):936-62. doi: 10.1016/j.cgh.2006.05.016. Epub 2006 Jul 14.
PubMed 16844425
Shaw T, Locarnini S. Entecavir for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004 Dec;2(6):853-71. doi: 10.1586/14789072.2.6.853.
PubMed 15566330
Chan HL, Heathcote EJ, Marcellin P, Lai CL, Cho M, Moon YM, Chao YC, Myers RP, Minuk GY, Jeffers L, Sievert W, Bzowej N, Harb G, Kaiser R, Qiao XJ, Brown NA; 018 Study Group. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Ann Intern Med. 2007 Dec 4;147(11):745-54. doi: 10.7326/0003-4819-147-11-200712040-00183. Epub 2007 Oct 1.
PubMed 17909201
Keeffe EB, Zeuzem S, Koff RS, Dieterich DT, Esteban-Mur R, Gane EJ, Jacobson IM, Lim SG, Naoumov N, Marcellin P, Piratvisuth T, Zoulim F. Report of an international workshop: Roadmap for management of patients receiving oral therapy for chronic hepatitis B. Clin Gastroenterol Hepatol. 2007 Aug;5(8):890-7. doi: 10.1016/j.cgh.2007.05.004. Epub 2007 Jul 13.
PubMed 17632041
Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology. 2006 Dec;44(6):1656-65. doi: 10.1002/hep.21422.
PubMed 17133475
Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, Wichroski MJ, Xu D, Yang J, Wilber RB, Colonno RJ. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009 May;49(5):1503-14. doi: 10.1002/hep.22841.
PubMed 19280622
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2673-81. doi: 10.1056/NEJMoa042957.
PubMed 15987916
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006 Dec;131(6):1743-51. doi: 10.1053/j.gastro.2006.09.020. Epub 2006 Sep 20.
PubMed 17087951
Ha NB, Ha NB, Garcia RT, Trinh HN, Vu AA, Nguyen HA, Nguyen KK, Levitt BS, Nguyen MH. Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil. Hepatology. 2009 Sep;50(3):727-34. doi: 10.1002/hep.23044.
PubMed 19517525
Nguyen NH, Trinh HN, Nguyen TT, Do ST, Tran P, Nguyen HA, Nguyen KK, Garcia RT, Lutchman GA, Nguyen MH. Safety and efficacy of entecavir in adefovir-experienced patients. J Gastroenterol Hepatol. 2015 Jan;30(1):43-50. doi: 10.1111/jgh.12728.
PubMed 25168842

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

All Hepatitis B trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: HBV Viral Suppression by Entecavir in Adefovir Partial Responders
ClinicalTrials.gov ID: NCT00704106
Acronym / sponsor ID: ADVPR / PHF008
Conditions: Hepatitis B
Keywords: Hepatitis B, HBV, Treatment
Study type: Observational
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: Pacific Health FoundationUniversity, hospital or other
Collaborators: Bristol-Myers Squibb
Study start: May 2008
Primary completion: Oct 2011 (actual)
Study completion: Oct 2011 (actual)
First posted: 24 Jun 2008 (estimated)
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.

Detailed description

Study design

Observational model: Cohort
Time perspective: Other
Number of arms: 4

Arm	Type	Receives
Group 1	–	Drug: EntecavirPersistent viremia after 48 weeks or longer.
Group 2	–	Drug: Entecavir<2 log IU/mL drop from initial HBVDNA after 12 weeks of adefovir
Group 3	–	Drug: EntecavirPatients who responded to adefovir and were switched to entecavir.
Group 4	–	Drug: EntecavirPatients with 160 copies/mL (100 IU/mL) or higher at the time of medication switch.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: * Age 18 years or older * All genders and ethnicity * Positive HBsAg * HBeAg positive and negative * Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed) * Patients who are switched to, or prescribed, entecavir after treatment with adefovir for at least 12 weeks by the providing physician * Patients with and without prior lamivudine exposure will be enrolled but enrollment of lamivudine experienced cases will be limited to no more than 30 patients total

Key inclusion criteria (7 listed)

Age 18 years or older
All genders and ethnicity
Positive HBsAg
HBeAg positive and negative
Pretreatment HBV DNA of 10,000 copies/mL or higher (for purposes of this study, both copies and equivalent IU measurements will be recorded and analyzed)

Key exclusion criteria (9 listed)

Patients who refused to consent to the study
Patients younger than 18
Vulnerable subjects such as pregnant women, prisoners, employees, patients with significant cognitive deficits.
Patients with prior exposure to another nucleoside for more than 2 weeks. Those with prior exposure to lamivudine will be enrolled under conditions detailed above.
HIV co-infection

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
EntecavirAlso: Baraclude0.5 or 1 mg dose qd	Drug	Group 1, Group 2, Group 3, Group 4

Primary outcome

HBV DNA PCR after 12 weeks of entecavir from the time of medication switching: percent of patients with <2log drop in HBV DNA and percent of patients with complete viral suppression during adefovir versus during entecavir.
Time frame: 48 weeks or after

4 secondary outcomes

HBV DNA PCR after 24 weeks of entecavir from the time of medication switching.
Time frame: 48 weeks or after
HBV DNA PCR after 48 weeks of entecavir from the time of medication switching.
Time frame: 48 weeks or after
BR and CR at 24 and 48 weeks of therapy with entecavir.
Time frame: 48 weeks or after.
BR and CR for longer duration of therapy if available.
Time frame: 48 weeks or after.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2022.
Background: PubMed 16103976McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25 Suppl 1:3-8. doi: 10.1055/s-2005-915644.
Background: PubMed 16391218Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
Background: PubMed 16530509Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.
Background: PubMed 15470215Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
Background: PubMed 17256718Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available.
Background: PubMed 16844425Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update. Clin Gastroenterol Hepatol. 2006 Aug;4(8):936-62. doi: 10.1016/j.cgh.2006.05.016. Epub 2006 Jul 14.
Background: PubMed 15566330Shaw T, Locarnini S. Entecavir for the treatment of chronic hepatitis B. Expert Rev Anti Infect Ther. 2004 Dec;2(6):853-71. doi: 10.1586/14789072.2.6.853.
Background: PubMed 17909201Chan HL, Heathcote EJ, Marcellin P, Lai CL, Cho M, Moon YM, Chao YC, Myers RP, Minuk GY, Jeffers L, Sievert W, Bzowej N, Harb G, Kaiser R, Qiao XJ, Brown NA; 018 Study Group. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Ann Intern Med. 2007 Dec 4;147(11):745-54. doi: 10.7326/0003-4819-147-11-200712040-00183. Epub 2007 Oct 1.
Background: PubMed 17632041Keeffe EB, Zeuzem S, Koff RS, Dieterich DT, Esteban-Mur R, Gane EJ, Jacobson IM, Lim SG, Naoumov N, Marcellin P, Piratvisuth T, Zoulim F. Report of an international workshop: Roadmap for management of patients receiving oral therapy for chronic hepatitis B. Clin Gastroenterol Hepatol. 2007 Aug;5(8):890-7. doi: 10.1016/j.cgh.2007.05.004. Epub 2007 Jul 13.
Background: PubMed 17133475Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ. Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology. 2006 Dec;44(6):1656-65. doi: 10.1002/hep.21422.
Background: PubMed 19280622Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, Fang J, Wichroski MJ, Xu D, Yang J, Wilber RB, Colonno RJ. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology. 2009 May;49(5):1503-14. doi: 10.1002/hep.22841.
Background: PubMed 15987916Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2673-81. doi: 10.1056/NEJMoa042957.

Related trials for Hepatitis B

Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B

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.

Huy N Trinh, M.D. principal investigator

Pacific Health Foundation

Mindie H Nguyen, M.D., M.A.S. principal investigator

Pacific Health Foundation

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Hepatitis B, run by Pacific Health Foundation at 6 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 7 inclusion and 9 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 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

HBV DNA PCR after 12 weeks of entecavir from the time of medication switching: percent of patients with <2log drop in HBV DNA and percent of patients with complete viral suppression during adefovir versus during entecavir. (time frame: 48 weeks or after). 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 NCT00704106, which also lists 15 linked publications.

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 14 Nov 2022.