Clinical trial NCT02607930: Study to Evaluate the Safety and Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in Human Immunodeficiency Virus-1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults
Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9883/Emtricitabine/Tenofovir Alafenamide Versus Abacavir/Dolutegravir/Lamivudine in HIV-1 Infected, Antiretroviral Treatment-Naive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1 Infection
Keywords: HIV
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-18
Enrollment: 631
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of a fixed dose combination (FDC) containing bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus a FDC containing abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in HIV-1 infected, antiretroviral treatment naive-adults.


Eligibility criteria: Key Inclusion Criteria:

* Antiretroviral treatment naive (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) except the use for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), up to one month prior to screening
* Plasma HIV-1 ribonucleic acid (RNA) levels ≥ 500 copies per milliliter (mL) at screening
* Adequate renal function: Estimated glomerular filtration rate ≥ 50 milliliter per minute (mL/min) (≥ 0.83 milliliter per second \[mL/sec\]) according to the Cockcroft-Gault formula
* Negative screening test for human leukocyte antigen (HLA) -B x 5701 allele provided by Gilead Sciences

Key Exclusion Criteria:

* An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening (refer to study protocol)
* Decompensated cirrhosis (e.g, ascites, encephalopathy, or variceal bleeding)
* Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
* Females who are pregnant (as confirmed by positive serum pregnancy test)
* Females who are breastfeeding
* Chronic Hepatitis B Virus (HBV) infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 144
measure: Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 96 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants Who Achieved HIV-1 RNA < 20 Copies/mL at Week 144 as Defined by the US FDA-Defined Snapshot Algorithm
timeFrame: Week 144
measure: Change From Baseline in log10 HIV-1 RNA at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in log10 HIV-1 RNA at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in log10 HIV-1 RNA at Week 144
timeFrame: Baseline, Week 144
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 144
timeFrame: Baseline, Week 144
measure: Percentage Change From Baseline in Hip BMD at Week 48
timeFrame: Baseline, Week 48
measure: Percentage Change From Baseline in Hip BMD at Week 96
timeFrame: Baseline, Week 96
measure: Percentage Change From Baseline in Hip BMD at Week 144
timeFrame: Baseline, Week 144
measure: Percentage Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline, Week 48
measure: Percentage Change From Baseline in Spine BMD at Week 96
timeFrame: Baseline, Week 96
measure: Percentage Change From Baseline in Spine BMD at Week 144
timeFrame: Baseline, Week 144
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Excluded Algorithm
timeFrame: Baseline, open-label Week 48
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 48 Open-Label as Defined by Missing = Failure Algorithm
timeFrame: Baseline, open-label Week 48
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Excluded Algorithm
timeFrame: Baseline, open-label Week 96
measure: Percentage of Participants Who Achieved HIV-1 RNA < 50 Copies/mL at Week 96 Open-Label as Defined by Missing = Failure Algorithm
timeFrame: Baseline, open-label Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 48 Open-Label
timeFrame: Baseline, open-label Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96 Open-Label
timeFrame: Baseline, open-label Week 96
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Phoenix
country: United States
facility: Pueblo Family Physicians
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony Martin Mills MD A Medical Corporation, DBA Mills Clinical Research
state: California
city: Oakland
country: United States
facility: Alameda Health System- Highland Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: San Diego
country: United States
facility: La Playa Medical Group
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente
state: California
city: Torrance
country: United States
facility: The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Center
state: California
city: Denver
country: United States
facility: Apex Research
state: Colorado
city: Washington
country: United States
facility: Whitman-Walker Institute
state: District of Columbia
city: Washington
country: United States
facility: Providence Hospital - DC
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates
state: District of Columbia
city: Washington
country: United States
facility: Medical Faculty Associates
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Therafirst Medical Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, M.D., P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami
country: United States
facility: AHF Kinder Medical Group
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Pensacola
country: United States
facility: AIDS Healthcare Foundation-Miami Beach
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprehensive Research Institute
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research and Treatment Center of the Treasure Coast
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Infectious Disease Group PC
state: Georgia
city: Atlanta
country: United States
facility: Aids Research Consortium of Atlanta Inc
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department
state: Georgia
city: Indianapolis
country: United States
facility: Indiana CTSI Clinical Research Center
state: Indiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City CARE Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Clinical Research Group, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare Inc
state: Missouri
city: Newark
country: United States
facility: Prime healthcare services - St Michael's LLC d/b/a Saint Michael's medical center
state: New Jersey
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Santa Fe
country: United States
state: New Mexico
city: Albany
country: United States
facility: Upstate Infectious Disease Associates
state: New York
city: Bronx
country: United States
facility: Bronx Care
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: Evergreen Health
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital-(Manhasset)
state: New York
city: Chapel Hill
country: United States
facility: Aids Research Consortium of Atlanta Inc
state: North Carolina
city: Charlotte
country: United States
facility: ID Consultants PA
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center - PPDS
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Research Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Columbia
country: United States
facility: Medical University of South Carolina PPDS
state: South Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: Saint Hope Foundation Inc
state: Texas
city: Dallas
country: United States
facility: AIDS Arms Inc
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Clinical Trials Office
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants PA
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts
state: Texas
city: Houston
country: United States
facility: Gordon E Crofoot MD PA
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: Longview
country: United States
facility: Diagnostic Clinic of Longview Center For Clinical Research (DCOL)
state: Texas
city: Seattle
country: United States
facility: Peter Shalit MD
state: Washington
city: Spokane
country: United States
facility: Multicare Rockwood HIV Critical Care Clinic
state: Washington
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin, Inc.
state: Wisconsin
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ghent
country: Belgium
facility: UZ Gent
city: Montreal
country: Canada
facility: Clinique Medicale L'actuel
city: Montreal
country: Canada
facility: McGill University Health Center
city: Montreal
country: Canada
facility: Clinique OPUS Inc
city: Ottawa
country: Canada
facility: Ottawa Hospital
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Toronto
country: Canada
facility: Maple Leaf Research
city: Vancouver
country: Canada
facility: Spectrum Health Care
city: Winnipeg
country: Canada
facility: Winnipeg Regional Health Authority
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dominicano de Estudios Virologicos IDEV
city: Lyon cedex 04
country: France
facility: Hôpital de La Croix Rousse
city: Nice
country: France
facility: CHU de Nice Archet I
city: PARIS cedex 10
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Tourcoing
country: France
facility: Groupe Hospitalier Bichat Claude Bernard
city: Berlin
country: Germany
facility: zibp Zentrum für Infektiologie Berlin Prenzlauer Berg GmbH
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Hamburg
country: Germany
facility: ICH Study Center
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
city: Roma
country: Italy
facility: Istituto Nazionale Malattie Infettive Lazzaro Spallanzani IRCCS
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badalona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cordoba
country: Spain
facility: C.H. Regional Reina Sofia - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Vigo
country: Spain
facility: CHUVI - H.U. Alvaro Cunqueiro
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Brighton
country: United Kingdom
facility: Brighton and Sussex University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust, Royal London Hospital, Ambrose King Centre
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster NHS Trust
city: London
country: United Kingdom
facility: Mortimer Market Centre
city: Manchester
country: United Kingdom
facility: North Manchester General Hospital - PPDS
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Wohl D, Clarke A, Maggiolo F, Garner W, Laouri M, Martin H, Quirk E. Patient-Reported Symptoms Over 48 Weeks Among Participants in Randomized, Double-Blind, Phase III Non-inferiority Trials of Adults with HIV on Co-formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide versus Co-formulated Abacavir, Dolutegravir, and Lamivudine. Patient. 2018 Oct;11(5):561-573. doi: 10.1007/s40271-018-0322-8.
citation: Wohl DA, Yazdanpanah Y, Baumgarten A, Clarke A, Thompson MA, Brinson C, Hagins D, Ramgopal MN, Antinori A, Wei X, Acosta R, Collins SE, Brainard D, Martin H. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019 Jun;6(6):e355-e363. doi: 10.1016/S2352-3018(19)30077-3. Epub 2019 May 5.
citation: Acosta RK, Willkom M, Martin R, Chang S, Wei X, Garner W, Lutz J, Majeed S, SenGupta D, Martin H, Quirk E, White KL. Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02533-18. doi: 10.1128/AAC.02533-18. Print 2019 May.
citation: Acosta R, Willkom M, Martin R, Chang S, Liu X, Hedskog C, et al. Low-frequency resistance variants in art-naïve participants do not affect bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) triple therapy outcome. [Poster MOPEB242]. 10th IAS Conference on HIV Science (IAS 2019); 2019 July 21-24; Mexico City, Mexico.
citation: Acosta R, White K, Garner W, Wei X, Andreatta K, Willkom M, et al. HIV-1 subtype (B or non-B) had no impact on the efficacy of B/F/TAF or resistance development in five phase 3 treatment-naïve or switch studies. [Poster THPEB077]. 22nd International AIDS Conference; 2018 July 23-27; Amsterdam, Netherlands.
citation: White K, Kulkarni R, Willkom M, Martin R, Chang S, Wei X, et al. Pooled week 48 efficacy and baseline resistance: B/F/TAF in treatment-naive patients. [Poster 532]. Conference on Retroviruses and Opportunistic Infections; 2018 March 4-7; Boston, USA.
citation: Gallant J, Lazzarin A, Mills A, Orkin C, Podzamczer D, Tebas P, Girard PM, Brar I, Daar ES, Wohl D, Rockstroh J, Wei X, Custodio J, White K, Martin H, Cheng A, Quirk E. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2063-2072. doi: 10.1016/S0140-6736(17)32299-7. Epub 2017 Aug 31.
citation: Orkin C, DeJesus E, Sax PE, Arribas JR, Gupta SK, Martorell C, Stephens JL, Stellbrink HJ, Wohl D, Maggiolo F, Thompson MA, Podzamczer D, Hagins D, Flamm JA, Brinson C, Clarke A, Huang H, Acosta R, Brainard DM, Collins SE, Martin H; GS-US-380-1489; GS-US-380-1490 study investigators. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV. 2020 Jun;7(6):e389-e400. doi: 10.1016/S2352-3018(20)30099-0.
citation: Acosta R, Andreatta K, D'Antoni M, Collins S, Martin H, White K. HIV Viral Blips in Adults Treated with INSTI-Based Regimens Through 144 Weeks. [Poster 540]. Conference on Retroviruses and Opportunistic Infections 2020 (CROI 2020); 2020 March 8-11; Boston, Massachusetts.
citation: Mills A, Gupta SK, Brinson C, Workowski K, Clarke A, Antinori A, Stephens JL, et al. 144-Week Efficacy and Safety of B/F/TAF in Treatment-Naive Adults Age ≥50 Years. [Poster 477]. Conference on Retroviruses and Opportunistic Infections 2020 (CROI 2020); 2020 March 8-11; Boston, Massachusetts.
citation: Ramgopal M, Maggiolo F, Ward D, Leboucche B, Rizzardini G, Molina JM, et al. Pooled Analysis of 4 International Trials of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Adults Aged ≥ 65 Years Demonstrating Safety and Efficacy: Week 48 Results. [Oral OAB0403].AIDS 2020; 2020 July 6-10; Virtual.
citation: Acosta R, Andreatta K, D'Antoni M, Collins S, Martin H, White K. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) shows high efficacy in clinical study participants infected with HIV-1 subtype F. [Poster P124]. HIV Drug Therapy 2020 (HIV Glasgow 2020); 2020 October 5-8; Glasgow, United Kingdom.
citation: Workowski K, Orkin C, Sax P, Hagins D, Koenig E, Stephens JL, et al. Four-Year Outcomes of B/F/TAF in Treatment-Naïve Adults [Poster 415]. Conference on Retroviruses and Opportunistic Infections 2021 (CROI 2021); 2021 June 3-November 3; Virtual.
citation: Acosta RK, Chen GQ, Chang S, Martin R, Wang X, Huang H, Brainard D, Collins SE, Martin H, White KL. Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants. J Antimicrob Chemother. 2021 Jul 15;76(8):2153-2157. doi: 10.1093/jac/dkab115.
citation: Arribas J, Orkin C, Maggiolo F, Antinori A, Lazzarin A, Yasdanpanah, et al. Long-term Analysis of B/F/TAF in Treatment-Naïve Adults Living With HIV Through Four Years of Follow-up. [PEB151]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21; Virtual.
citation: Acosta R, Chen G, Qin L, Wang X, Huang H, Hindman J, et al. Achievement of Undetectable HIV-1 RNA in the B/F/TAF Treatment-Naïve Clinical Trials. [Poster PEB150]. 11th IAS Conference on HIV Science (IAS 2021); 2021 July 18-21; Virtual.
citation: Acosta R, Chen G, Chang S, Martin R, Wang X, Huang H, et al. HIV with Transmitted Drug Resistance Is Durably Suppressed by B/F/TAF at Week 144. [Poster 430]. Conference on Retroviruses and Opportunistic Infections 2021 (CROI 2021); 2021 June 3-November 3; Virtual.
citation: Acosta R, Chen G, Huang H, Liu H, White K. Unreturned Pill Bottles in the 1489 and 1490 Clinical Trials: An Important Measure of Poor Adherence That Is Often Ignored in Pill Count Calculations. [Poster 902]. IDWeek 2021; 2021 September 29-October 3; Virtual.
citation: Daar E, Orkin C, Sax P, Stephens J, Koenig E, Clarke A, et al. Incidence of Metabolic Complications Among Treatment-naïve Adults Living With HIV-1 Randomized to B/F/TAF, DTG/ABC/3TC or DTG + F/TAF After 3 Years. [Oral 69]. IDWeek 2021; 2021 September 29-October 3; Virtual.
citation: Pozniak A, et al. Outcomes 48 Weeks After Switching From DTG/ABC/3TC or DTG + F/TAF to B/F/TAF. [PE2/68]. 18th European AIDS Conference (EAC 2021), 2021 October 27-30; London, United Kingdom.