Study to Evaluate Imetelstat (GRN163L) in Subjects With International Prognostic Scoring System (IPSS) Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Geron Corporation (Industry)
Overall Status
Recruiting ID
Anticipated Duration (Months)
Patients Per Site
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of imetelstat in transfusion dependent participants with low or intermediate-1 risk myelodysplastic syndrome (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment in Part 1 of the study and to compare the efficacy, in terms of red blood cell (RBC) transfusion independence (TI), of imetelstat to placebo in transfusion dependent participants with low or intermediate-1 risk MDS that is relapsed/refractory to ESA treatment in Part 2 of the study.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2/Phase 3

Detailed Description

This is a Phase 2/3, multicenter study of imetelstat that consists of 2 parts and approximately 270 participants may be enrolled.

Part 1 is an open-label, single-arm design to assess the efficacy and safety of imetelstat. Approximately 55 participants were enrolled in Part 1, including the expansion cohort, and be followed-up for safety, hematologic improvement and reduction in transfusion requirement.

Part 2 is a double-blind, randomized design to compare the efficacy of imetelstat with placebo. In the main study in Part 2, 178 participants were enrolled and randomized in a 2:1 ratio to receive either imetelstat or placebo, respectively.

In a separate Ventricular Repolarization substudy of Part 2, approximately 45 participants will be enrolled and randomized 2:1 to receive either imetelstat or placebo. If after a minimum of 2 treatment cycles in the Ventricular Repolarization substudy, a participant has no significant change to pRBC transfusion burden or evidence of clinical benefit per Investigator, after discussion with the Sponsor the participant may be unblinded. If the participant was on placebo treatment, he/she may be permitted to start treatment with imetelstat.

Each part of the study will consist of 3 phases: a Screening phase (up to 28 days); a treatment phase; and a post-treatment follow-up phase which will continue until death, lost to follow-up, withdrawal of consent, or the End of the Study (whichever occurs first). The End of the Study is defined as 2 years after the study entry of the last participant in the main study of Part 2 or anytime the sponsor terminates the study, whichever comes first.

Study Design

Study Type:
Anticipated Enrollment :
278 participants
Intervention Model:
Parallel Assignment
Double (Participant, Investigator)
Primary Purpose:
Official Title:
A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects With IPSS Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS) That is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
Actual Study Start Date :
Nov 24, 2015
Anticipated Primary Completion Date :
Jan 15, 2023
Anticipated Study Completion Date :
Oct 13, 2023

Arms and Interventions

Experimental: Part 1: Imetelstat

Imetelstat will be administered at a starting dose of 7.5 milligram per kilogram (mg/kg) given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

Drug: Imetelstat
Intravenous injection.
Other Names:
  • GRN163L
  • Experimental: Part 2 (Main Study): Imetelstat

    Imetelstat will be administered at a starting dose of 7.5 mg/kg given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

    Drug: Imetelstat
    Intravenous injection.
    Other Names:
  • GRN163L
  • Placebo Comparator: Part 2 (Main Study): Placebo

    Matching Placebo to Imetelstat will be administered.

    Drug: Placebo
    Matching Placebo to Imetelstat will be administered.

    Experimental: Part 2 (Ventricular Repolarization Substudy): Imetelstat

    Imetelstat will be administered at a starting dose of 7.5 mg/kg given intravenously every 4 weeks, until disease progression, unacceptable toxicity, or withdrawal of consent, or lack of response.

    Drug: Imetelstat
    Intravenous injection.
    Other Names:
  • GRN163L
  • Placebo Comparator: Part 2 (Ventricular Repolarization Substudy): Placebo

    Matching Placebo to Imetelstat will be administered.

    Drug: Placebo
    Matching Placebo to Imetelstat will be administered.

    Outcome Measures

    Primary Outcome Measures

    1. Part 1 and Part 2 (Main Study): Percentage of Participants Without any Red Blood Cell (RBC) Transfusion During any Consecutive 8-Week Period [Approximately 12 months]

    Secondary Outcome Measures

    1. Number of Participants with Adverse Events (AEs) [During study (approximately 2 years)]

    2. Percentage of Participants Without any RBC Transfusion During any Consecutive 24-Week Period [During study (approximately 2 years)]

    3. Time to the 8-Week RBC Transfusion Independence (TI) [During study (approximately 2 years)]

    4. Duration of RBC TI [During study (approximately 2 years)]

    5. Percentage of Participants with Hematologic Improvement [During study (approximately 2 years)]

    6. Percentage of Participants with Complete Remission (CR) or Partial Remission (PR) as Per International Working Group (IWG) Response Criteria 2006 [During study (approximately 2 years)]

    7. Overall Survival [During study (approximately 2 years)]

    8. Progression Free Survival (PFS) [During study (approximately 2 years)]

      Progression free survival will be assessed as the time interval from study Day 1 to the first date of disease progression or death from any cause, whichever occurs first. As per IWG criteria disease progression is defined as: at least one of the following: at least 50 percent (%) decrement from maximum response levels in granulocytes or platelets; reduction in hemoglobin by greater than or equal to (>=) 1.5 gram per deciliter (g/dL); transfusion dependence.

    9. Time to Progression to Acute Myeloid Leukemia [During study (approximately 2 years)]

    10. Amount of RBC Transfusions [During study (approximately 2 years)]

    11. Relative Change in RBC Transfusions [During study (approximately 2 years)]

    12. Percentage of Participants Receiving any Myeloid Growth Factors [During study (approximately 2 years)]

    13. Maximum Observed Plasma Concentration (Cmax) [During study (approximately 2 years)]

    14. Area Under the Drug Concentration-Plasma Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) [During study (approximately 2 years)]

    15. Percentage of Participants with Antibodies to Imetelstat [During study (approximately 2 years)]

    16. Part 2 (Main Study): Medical Resource Utilization Data [During study (approximately 2 years)]

    17. Part 2 (Main Study): Assessment of Functional Assessment of Cancer Therapy-Anemia-Related Effects (FACT-An) [During study (approximately 2 years)]

      The Functional Assessment of Cancer Therapy Anemia (FACT-An), is included in order to provide an assessment of the subject's functional status, well-being, and symptoms over time.

    18. Part 2 (Main Study): Assessment of EuroQol 5 Dimension Questionnaire (EQ-5D-5L) [During study (approximately 2 years)]

      The EQ-5D-5L is a generic measure of health status. EQ-5D-5L is a 5 item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).

    19. Part 2 (Main Study): Assessment of Quality of Life in Myelodysplasia Scale (QUALMS) [During study (approximately 2 years)]

      The QUALMS is a 38-item measure that assesses health-related quality of life for patients with MDS. Thirty-three items are used to calculate the total score, as well as the 14 item physical burden (QUALMS-P), 3-item benefit-finding (QUALMS-BF), and 11-item emotional burden (QUALMS-E) subscales.

    20. Part 2 (Main Study): Assessment of Participant Global Impression of Change (PGIC) [During study (approximately 2 years)]

      The Participant Global Impression of Change (PGIC) is a single-item questionnaire designed to provide an overall assessment of treatment from the participant's perspective since the start of the study. It is measured on a 7-point scale, where 1=very much improved and 7=very much worse. A participant is considered a responder if they have a response of "very much improved" or "much improved".

    21. Part 2 (Ventricular Repolarization Substudy): Change in QT Interval by Fridericia's Correction Method [Baseline and Day 1]

      Change from baseline in QTc interval by Fridericia's correction method (ΔQTcF) will be assessed in participants in the Ventricular Repolarization substudy.

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Man or woman greater than or equal to (>=) 18 years of age

    • Diagnosis of myelodysplastic syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to Cycle 1 Day 1 (C1D1) (Part 1) or randomization [Part 2 (Main Study)]. In Part 2 (Ventricular Repolarization Substudy), diagnosis of MDS or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) according to WHO criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to C1D1

    • International Prognostic Scoring System (IPSS) low Risk or intermediate-1 risk MDS

    • Red blood cell (RBC) transfusion dependent, defined as requiring at least 4 RBC units transfused over an 8-week period during the 16 weeks prior to Study Entry; pre-transfusion hemoglobin (Hb) should be less than or equal to 9.0 gram per deciliter (g/dL) to count towards the 4 units total

    • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

    Exclusion Criteria:
    • Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients

    • Participant has received an investigational drug or used an invasive investigational medical device within 30 days prior to Study Entry or is currently enrolled in an investigational study

    • Prior treatment with imetelstat

    • Have received corticosteroids greater than (>) 30 milligram per day (mg/day) prednisone or equivalent, or growth factor treatment within 4 weeks prior to study entry

    • Has received an erythropoiesis-stimulating agent (ESA) or any chemotherapy, immunomodulatory, or immunosuppressive therapy within 4 weeks prior to study entry (8 weeks for long-acting ESAs)

    • Part 2 (Main Study): a) Prior treatment with a hypomethylating agent (example [eg], azacitidine, decitabine); b) Prior treatment with lenalidomide

    Additional Exclusion Criteria for Part 2 (Ventricular Repolarization Substudy)

    • Concurrent therapy with medications known to prolong the QT interval and have been associated with Torsade de pointes arrythmia (TdP)

    • Cardiac function abnormalities on screening ECG as follows:

    • Resting heart rate outside of 50 to 100 beats per minute

    • QTcF >470 millisecond (msec) determined by central assessment based on the average value of a triplicate set of ECGs

    • Diagnosed or suspected congenital long QT syndrome

    • Family history of sudden unexpected death from cardiac-related causes if indicative of a pathogenic mutation of cardiac ion channels

    • Family history of congenital long QT syndrome

    • History of Mobitz II second degree or third degree heart block

    • Implantable pacemaker or automatic implantable cardioverter defibrillator

    • Complete bundle branch block or ventricular conduction delay (QRS >119 msec)

    • Chronic or persistent atrial arrhythmia including atrial fibrillation and atrial flutter

    • History or presence of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia

    • Unusual T-wave morphology (i.e., bifid T-wave) likely to interfere with QT measurements

    • History or evidence for any of the following: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (example, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) within 12 months prior to Cycle 1 Day 1, New York Heart Association (NYHA) Class II to IV heart disease

    • Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥100 mmHg). Participants with a history of hypertension are permitted, provided that BP is controlled to within these limits by anti-hypertensive treatment

    • Any skin condition likely to interfere with electrocardiographic electrode placement or adhesion

    • History of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues

    Contacts and Locations


    SiteCityStateCountryPostal Code
    1UAB Comprehensive Cancer CenterBirminghamAlabamaUnited States35294
    2Acrc/Arizona Clinical Research, Inc.TucsonArizonaUnited States85715
    3CBCC Global Research, IncBakersfieldCaliforniaUnited States93309
    4UCLA Ronald Regan Medical CenterLos AngelesCaliforniaUnited States90095
    5Yale-New Haven Hospital (YNHH) - Smilow Cancer HospitalNew HavenConnecticutUnited States06510-3220
    6BRCR Medical CenterPlantationFloridaUnited States33326
    7University of South Florida (USF) - H. Lee Moffitt Cancer CenterTampaFloridaUnited States33612
    8University of ChicagoChicagoIllinoisUnited States60637-1426
    9Franciscan HealthIndianapolisIndianaUnited States46237-8601
    10St. Agnes Healthcare, IncBaltimoreMarylandUnited States21229-5201
    11Center for Cancer and Blood DisordersBethesdaMarylandUnited States20817
    12Mayo Clinic RochesterRochesterMinnesotaUnited States55902
    13Washington University School of MedicineSaint LouisMissouriUnited States63110
    14University of New Mexico Cancer CenterAlbuquerqueNew MexicoUnited States87131
    15Icahn School of Medicine at Mount Sinai Program for the Protection of Human SubjectsNew YorkNew YorkUnited States10029
    16Columbia PresbyterianNew YorkNew YorkUnited States10032
    17Columbia University Medical CenterNew YorkNew YorkUnited States10032
    18Weill Cornell Medical College-New York Presbyterian HospitalNew YorkNew YorkUnited States10065
    19Cleveland Clinic Taussig CancerClevelandOhioUnited States44195
    20The Ohio State Comprehensive Cancer CenterColumbusOhioUnited States43210
    21Prairie lakes Healthcare system, IncWatertownSouth DakotaUnited States57201
    22Tennessee Oncology at Centennial Medical CenterNashvilleTennesseeUnited States37203
    23Vanderbilt University Medical - Hematology-OncologyNashvilleTennesseeUnited States37232-6307
    24Texas Oncology/Methodist Charlton Cancer CenterDallasTexasUnited States75237
    25Simmons Comprehensive Cancer CenterDallasTexasUnited States75390
    26Fred Hutchinson Cancer Research Center (FHCRC)SeattleWashingtonUnited States98109-1024
    27UZ GentGhentOost-VlaanderenBelgium9000
    28AZ Sint-Jan Burgge-OostendeBruggeWest-VlaanderenBelgium8000
    29ZNA MiddelheimAntwerpenBelgium2020
    30ZNA Stuyvenberg AntwerpenAntwerpenBelgium2610
    31AZ KlinaBrasschaatBelgium2930
    32Algemeen Ziekenhuis Sint-JanBruggeBelgium8000
    33Universitair Ziekenhuis GentGentBelgium9000
    34Az GroeningeKortrijkBelgium8500
    35UZ Leuven - Campus GasthuisbergLeuvenBelgium3000
    36GZA Ziekenhuizen - Campus SintWilrijkBelgium
    37Tom Baker Cancer CentreCalgaryAlbertaCanadaT2N 4N2
    38University of Alberta Hospital - Hematology ResearchEdmontonAlbertaCanadaT6G 2R3
    39The Ottawa HospitalOttawaOntarioCanadaK1G 8L6
    40Princess Margaret HospitalTorontoOntarioCanadaM5G 2L7
    41Jewish General HospitalMontréalQuebecCanadaH3T 1E2
    42Sunnybrook Health Sciences CentreTorontoCanadaM4N 3M5
    43Fakultni nemocnice BrnoBrnoBrno-městoCzechia625 00
    44FN Hradec KraloveHradec KrálovéCzechia50005
    45FN Kralovske VinohradyPraha 10Czechia100 34
    46Vseobecna fakultni nemocnice v PrazePraha 2Czechia128 08
    47Hopital de l'ArchetNiceAlpes-MaritimesFrance6202
    48CHU ToursToursCentreFrance37044
    49CHU de Grenoble - Hôpital AlbeLa TroncheIsèreFrance38700
    50CHRU Nancy BraboisVandœuvre-lès-NancyMeurthe-et-MoselleFrance54511
    51CH Le Mans - HAEMATOLOGYLe MansSartheFrance72037
    52Hopital Paul Brousse - Aphp Hôpitaux Universitaires Paris SuVillejuifVal-de-MarneFrance94804
    53CHU de PoitiersPoitiersVienneFrance86021
    54Centre Hospitalier UniversitaiAngersFrance49100
    55CHRU de Lille - Hopital Claude Huriez - Maladies du SangLilleFrance59037
    56CHU - Hôpital Saint Louis - HParisÎle-de-FranceFrance75010
    57University Hospital FreiburgFreiburgBaden-WürttembergGermany79106
    58Fachärztliche Gemeinschaftspraxis mit SchwerpunktDresdenSachsenGermany1307
    59University Hospital LeipzigLeipzigSachsenGermany4107
    60Studienzentrum für Hämatologie, Onkologie,Diabetologie, Endoskopie und FußambulanzAschaffenburgGermany63739
    61University Hospital BonnBonnGermany53127
    62Universitatsklinikum Carl Gustav Carcus DresdenDresdenGermany01307
    63Universitätsklinikum DüsseldorfDuesseldorfGermany40225
    64Universitaetsklinikum KoelnKoelnGermany50937
    65Johannes Gutenberg UniversitätMainzGermany55131
    66Klinikum rechts der Isar an der Technischen Universität MünchenMünchenGermany81675
    67Universitaetsklinikum UlmUlmGermany89081
    68Kaplan Medical CenterReẖovotHagalil SaintIsrael7610001
    69The Edith Wolfson Medical CenterH̱olonHaMerkazIsrael58100
    70Meir Medical CenterKfar SabaHaMerkazIsrael44281
    71Ha'Emek Medical CenterAfulaHaZafonIsrael1834111
    72Tel Aviv Sourasky Medical CenterTel AvivTel-AvivIsrael49372
    73The Chaim Sheba Medical CenterTel HaShomerTel-AvivIsrael5265601
    74Carmel MCHaifaIsrael3436212
    75Hadassah Medical OrganizationJerusalemIsrael9112001
    76Rabin Medical Center, Beilinson HospitalPetah TikvaIsrael4941492
    77A.O. Ospedale Niguarda Ca' GrandaMilanoLombardiaItaly20162
    78Istituto Clinico Humanitas Rozzano, IRCCSRozzanoMilanoItaly20089
    79Irccs CrobRionero In VulturePotenzaItaly85028
    80AOU Ospedali Riuniti Umberto I G.M. Lancisi G. SalesiAnconaItaly60020
    81Policlinico Sant'Orsola MalpighiBolognaItaly40138
    82Azienda Ospedaliera Universitaria Careggi di FirenzeFirenzeItaly50134
    83IRCCS Policlinico San MatteoPaviaItaly27100
    84A.O. Ospedali Riuniti Marche Nord Presidio Ospedaliero S. Salvatore di Pesaro-Stabilim. di MuragliaPesaroItaly61122
    85Grande Ospedale Metropolitano 'Bianchi-Melacrino-Morelli' Reggio CalabriaReggio CalabriaItaly89124
    86A.O. Universitaria Policlinico Tor VergataRomaItaly00133
    87AO S. Andrea, Università degli Studi di Roma La SapienzaRomaItaly189
    88Ospedale di Circolo, PO VareseVareseItaly21100
    89Gachon University Gil Medical Center - oncologyIncheonIncheon Gwang'yeogsiKorea, Republic of21565
    90Pusan National University Hospital - Hematology and OncologySeoguIncheonKorea, Republic of42941
    91Chonnam National University Hwasun HospitalHwasunSouth JeollaKorea, Republic of58128
    92Seoul National University HospitalSeoulKorea, Republic of03080
    93Asan Medical CenterSeoulKorea, Republic of05505
    94Samsung Medical CenterSeoulKorea, Republic of06351
    95The Catholic University of Korea Seoul St. Mary's HospitalSeoulKorea, Republic of06591
    96Severance Hospital, Yonsei UniSeoulKorea, Republic of3722
    97Radboud UmcnNijmegenGelderlandNetherlands6525 GA
    98Meander Medisch CentrumAmersfoortNetherlands3813 TZ
    99VU Medisch CentrumAmsterdamNetherlands1081 HV
    100Universitair Medisch Centrum GroningenGroningenNetherlands9713 GZ
    101Uniwersytecki Szpital Kliniczny im. J. Mikulicza-RadeckiegoWrocławDolnoslaskiePoland50-367
    102Centrum Medyczne Pratia PoznanSkorzewoKościerzynaPoland60-185
    103Wojewódzki Szpital Specjalistyczny sp.z o.o.SłupskPomorskiePoland76-200
    104SPZOZ MSWiA z Warminsko - Mazurskim Centrum OnkologiiOlsztynWarminsko-mazurskiePoland10-228
    105Ars Medical sp. z o.o.PiłaWielkopolskie WojewództwoPoland64-920
    106Clinics of Samarskiy GMUSamaraVolgaRussian Federation443079
    107Emergency Hospital of DzerzhinskDzerzhinskRussian Federation606019
    108City Clinical HospitalMoscowRussian Federation129301
    109Nizhniy Novgorod Region Clinical HospitalNizhny NovgorodRussian Federation603126
    110Ryazan Regional Clinical HospitalRyazanRussian Federation390039
    111FGU-Russian Research InstitutSaint PetersburgRussian Federation191024
    112Oncologic Dispensary No.2SochiRussian Federation354057
    113H.U.Pta.del MarCadizCádizSpain11009
    114Hospital Universitario Puerta de Hierro MajadahondaMajadahondaMadridSpain28222
    115Hospital de CrucesBaracaldoVizcayaSpain48903
    116Hosp. Univ. Germans Trias I PujolBadalonaSpain08916
    117Hosp. Univ. Vall D HebronBarcelonaSpain08035
    118Hosp. Clinic I Provincial de BarcelonaBarcelonaSpain08036
    119Hosp. Gral. Univ. Gregorio MaranonMadridSpain28007
    120Hosp. Univ. La PazMadridSpain28046
    121Hosp. Clinico Univ. de SalamancaSalamancaSpain37007
    122Hospital Universitario Nuestra Señora de ValmeSevillaSpain41014
    123Hospital Universitario DoctorValenciaSpain46017
    124Hospital Universitari i Politecnic La FeValenciaSpain46026
    125University Hospital in BaselBaselBasel-Stadt (de)Switzerland4031
    126Kantonsspital St. Gallen - Onkologie/HämatologieSaint GallenSankt GallenSwitzerland9007
    127Inselspital - Universitätsspital BernBernSwitzerland3010
    128Universitaetsspital ZuerichZuerichSwitzerland8091
    129Ankara University Medical Faculty - HematologyAnkaraAnatoliaTurkey6590
    130Cukurova University Medical FacultyAdanaTurkey1330
    131Ege Universitesi Tip Fakultesi - HematologyİzmirTurkey35040
    132KZ "Miska bahatoprofilna klinichna likarnia No4", hematolohiDnipropetrovs'kDnipropetrovs'ka Oblast'Ukraine49102
    133Instytut patolohii krovi ta transfusiynoi medytsyny NAMN UkrLvivL'vivs'ka Oblast'Ukraine79044
    134KNP "Cherkaskyi oblasnyi onkolohichnyi dyspanser CherkaskoiCherkasyUkraine18009
    135Nottingham City Hospital - Clinical HaematologyNottinghamNottinghamshireUnited KingdomNG5 1PB
    136Aberdeen Royal InfirmaryAberdeenUnited KingdomAB252ZL
    137The Leeds Teaching Hospitals NHS TrustLeedsUnited KingdomLS9 7TF
    138Southampton University HospitalSouthamptonUnited KingdomSO16 6YD

    Sponsors and Collaborators

    • Geron Corporation


    • Study Director: Faye Feller, MD, Geron Corporation

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Geron Corporation Identifier:
    Other Study ID Numbers:
    • CR107947
    • 63935937MDS3001
    • 2015-002874-19
    First Posted:
    Nov 6, 2015
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by Geron Corporation
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 8, 2022