HIV InfectionsPhase 3NCT02227238
Comparative Efficacy and Safety Study of Dolutegravir and Lopinavir/Ritonavir in Second-line Treatment
A Phase 3 study testing DTG, LPV/RTV and Two NRTIs in people with HIV Infections, run by ViiV Healthcare at 59 sites in 13 countries.
Trial summary
For treatment of human immunodeficiency virus type 1(HIV-1), publicly funded programmes tend to follow World Health Organization (WHO) guidelines to use a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) for first-line antiretroviral therapy… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- DTG, LPV/RTV and Two NRTIs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 627 participants
- Where
- 59 sitesin 13 countries
- Study dates
- 11 Dec 2014to 14 Feb 2022
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infected subjects >=18 years of age.
- A female subject may be eligible to enter and participate in the study if she:
- is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, is of child-bearing potential, with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the protocol-defined methods of contraception to avoid pregnancy throughout the study and for at least 2 weeks after discontinuation of all study medication.
- HIV-1 infection as documented by HIV-1 RNA >=400 c/mL at Screening.
- Subject has been on a first-line treatment regimen consisting of an NNRTI plus two NRTIs for at least 6 months and is currently experiencing virologic failure to this first-line regimen defined as two consecutive (>=7 days apart) HIV-1 RNA results of >=400 c/mL.
- Subjects must receive at least one fully active agent within the dual-NRTI background regimen for second line treatment. Fully active is defined by the Screening genotypic resistance report of the central laboratory (or a laboratory contracted by the central laboratory) showing no evidence of full or of partial resistance for a given NRTI which will be taken on study.
- Subject is PI-naïve and Integrase inhibitor (INI)-naïve, defined as no prior or current exposure to any PI or INI.
- Subject or the subject's legal representative is willing and able to understand and provide signed and dated written informed consent prior to screening.
Who cannot join
- Women who are breastfeeding.
- Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic or current CD4+ cell levels <200 cells per cubic millimeter
- Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Anticipated need for hepatitis C virus (HCV) therapy during the Randomized Phase of the study.
- History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.
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- Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject.
- Subjects who in the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk.
- Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
- Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, systemically administered immunomodulators.
- Treatment with any agent, other than licensed ART as allowed above with documented activity against HIV-1 in vitro/vivo within 28 days of first dose of IP. The exception is use of entecavir, in appropriate clinical situations, for treatment of hepatitis B [e.g. prior intolerance to Tenofovir (TDF), viral resistance to lamivudine (3TC) / Emtricitabine (FTC)] after discussion and agreement between the investigator and the medical monitor.
- Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP.
- Any evidence of primary viral resistance to PIs or INIs based on the presence of any major resistance-associated mutation.
- The subject's virus does not yield results using genotype at Screening (assay data is essential for eligibility determination).
- Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 triglycerides. A single repeat test is allowed during the Screening period to verify a result.
- Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound.
- Alanine aminotransferase (ALT) >=5 times the upper limit of normal (ULN) or ALT >=3xULN and bilirubin >=1.5xULN (with >35% direct bilirubin)
Trial locations and contacts
59 sites in 13 countries.
59 sites in 13 countries
Russia10 sites
GSK Investigational Site
Barnaul, 656010
GSK Investigational Site
Kazan', 420061
GSK Investigational Site
Kemerovo, 650056
GSK Investigational Site
Krasnodar, 350015
GSK Investigational Site
Moscow, 105275
GSK Investigational Site
Moscow, 129110
GSK Investigational Site
Saint Petersburg, 190103
GSK Investigational Site
Smolensk, 214006
GSK Investigational Site
Toliyatti, 445846
GSK Investigational Site
Yekaterinburg, 620149
Argentina7 sites
GSK Investigational Site
Buenos Aires, 1141
GSK Investigational Site
Buenos Aires, C1221ADC
GSK Investigational Site
Buenos Aires, C1426ABP
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Buenos Aires, C1405CKC
GSK Investigational Site
Ciudad de Buenos Aires, Buenos Aires, C1202ABB
GSK Investigational Site
Córdoba, 5000
GSK Investigational Site
Rosario, Santa Fe Province, 2000
Romania5 sites
GSK Investigational Site
Bucharest, 021105
GSK Investigational Site
Bucharest, 030303
GSK Investigational Site
Cluj-Napoca, 400348
GSK Investigational Site
Constanța, 900708
GSK Investigational Site
Târgu Mureş, 540394
South Africa5 sites
GSK Investigational Site
Bloemfontein, 9301
GSK Investigational Site
Durban, 4001
GSK Investigational Site
Observatory, Cape Town, 7925
GSK Investigational Site
Soweto, Gauteng, 2013
GSK Investigational Site
Westdene, 2092
Thailand5 sites
GSK Investigational Site
Bangkok, 10330
GSK Investigational Site
Chiang Mai, 50200
GSK Investigational Site
Khon Kaen, 40002
GSK Investigational Site
Nonthaburi, 11000
GSK Investigational Site
Ratchatewi, 10400
Brazil4 sites
GSK Investigational Site
Rio de Janeiro, 21045900
GSK Investigational Site
Salvador, Estado de Bahia, 40110-010
GSK Investigational Site
São Paulo, São Paulo, 01246-090
GSK Investigational Site
São Paulo, 04121-000
Chile4 sites
GSK Investigational Site
Puente Alto - Santiago, Región Metro de Santiago, 8207257
GSK Investigational Site
Santiago, Región Metro de Santiago, 8330074
GSK Investigational Site
Santiago, Región Metro de Santiago, 8900088
GSK Investigational Site
Santiago, 8360159
China4 sites
GSK Investigational Site
Beijing, 100015
GSK Investigational Site
Beijing, 100069
GSK Investigational Site
Guangzhou, Guangdong, 510060
GSK Investigational Site
Shanghai, 201508
Mexico4 sites
GSK Investigational Site
Distrito Federal, 06470
GSK Investigational Site
Guadalajara, Jalisco, 44280
GSK Investigational Site
México, 14000
GSK Investigational Site
Mexico City, 03720
Peru4 sites
GSK Investigational Site
Callao, Callao 02
GSK Investigational Site
Lima, 1
GSK Investigational Site
Lima, 32
GSK Investigational Site
Lima, Lima 31
Ukraine4 sites
GSK Investigational Site
Kyiv, 03115
GSK Investigational Site
Odesa, 65031
GSK Investigational Site
Vinnytsia, 21021
GSK Investigational Site
Zaporizhzhya, 69006
Colombia2 sites
GSK Investigational Site
Bogotá, 111311
GSK Investigational Site
Bogotá, 5600520
About this study
Official title: A Phase 3b, Randomized, Open-label Study of the Antiviral Activity and Safety of Dolutegravir Compared to Lopinavir/Ritonavir Both Administered With Dual Nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1 Infected Adult Subjects With Treatment Failure on First Line Therapy
For treatment of human immunodeficiency virus type 1(HIV-1), publicly funded programmes tend to follow World Health Organization (WHO) guidelines to use a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) for first-line antiretroviral therapy (ART); however, there is a need for further data on the best treatment options for people with HIV-1 who have virological failure with this first-line regimen. The number of patients failing on their first-line regimen is increasing thereby requiring a switch to second-line treatment to reduce accumulation of drug-resistance mutations, disease progression, HIV transmission, and death. WHO guidelines recommend second-line antiretroviral therapy for adults consisting of two NRTIs + a ritonavir-boosted protease inhibitor (PI); atazanavir (ATV) plus ritonavir (RTV) or lopinavir (LPV)/RTV are the preferred boosted PI options. This study is conducted to demonstrate non-inferior antiviral activity at 48 weeks of a dolutegravir (DTG) containing regimen compared to a WHO-recommended standard of care regimen for second line treatment, LPV/RTV + two NRTIs, in HIV-1 infected patients failing first line therapy. This study comprises of a Screening Phase (approximately 28 to 42 days), a Randomized Phase (Day 1 to Week 48 plus a 4-week treatment extension), and a Continuation Phase. Approximately 612 subjects will be randomized 1:1 to receive DTG 50 milligram (mg) once daily or LPV/RTV (800/200 mg once daily or 400/100 mg twice daily, in accordance with investigator decision and local label), each added to an investigator selected background regimen of two NRTIs at least one of which needs to be fully active based on viral resistance testing at Screening. Subjects randomized to the LPV/RTV arm will either (i) continue receiving LPV/RTV and complete the study after the 4-week treatment extension at Week 52, or (ii) switch to the DTG arm prior to study completion at Week 52 and continue to have access to DTG in the Continuation Phase. Subjects randomized to receive DTG who successfully complete 52 weeks of treatment and subjects originally randomized to receive LPV/RTV but switched to DTG prior to Week 52 will continue to have access to DTG until it is either locally approved and commercial supplies are available to patients or the patient no longer derives clinical benefit, or the patient meets a protocol-defined reason for discontinuation.
- Conditions
- HIV Infections
- Being tested
- DTG, LPV/RTV, Two NRTIs
- Keywords
- integrase inhibitor, non-inferiority, dolutegravir, lopinavir/ritonavir, second-line treatment, HIV-1, antiretroviral therapy-experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTGDrug
DTG is supplied as 50 mg tablets
LPV/RTVDrug
LPV/RTV is supplied as the LPV/RTV oral tablet, which contains 200 mg of LPV and 50 mg of RTV
Two NRTIsDrug
Investigators will choose a dual NRTI background regimen for each subject . In consultation with the medical monitor, 3TC may be added as a third NRTI to a dual-NRTI background regimen in subjects with chronic HBV infection and evidence of HIV resistance to 3TC
| Study group | Role | What they receive |
|---|---|---|
| DTG arm | Experimental | Subjects will receive one oral tablet of 50 mg DTG once daily plus two NRTIs selected by the investigator Receives: Drug: DTG; Drug: Two NRTIs |
| LPV/RTV arm | Active comparator | Subjects will receive four oral tablets of200/50 mg LPV/RTV once daily or two oral tablets of 200/50 mg LPV/RTV twice daily plus two NRTIs selected by the investigator Receives: Drug: LPV/RTV; Drug: Two NRTIs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <50 Copies Per Milliliter (c/mL) at Week 48
Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior activity of DTG plus 2 NRTI's compared to LPV/RTV plus 2 NRTI's. Analysis was performed on Intent-to-treat exposed (ITT-E) Population, which comprised of all randomized participants who received at least one dose of study medication. Percentage values are rounded off.
Measured: Week 48
Secondary outcomes (36)
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24
Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to demonstrate the non-inferior activity of DTG plus 2 NRTI's compared to LPV/RTV plus 2 NRTI's. Percentage values are rounded off.
Measured: Week 24
Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Weeks 24 and 48
Percentage of participants with plasma HIV 1 RNA <400 c/mL at Week 24 and 48 using the FDA snapshot algorithm were evaluated. Percentage values are rounded off.
Measured: Week 24 and Week 48
Percentage of Participants Without Virologic or Tolerability Failure at Week 24 and Week 48
Virologic or tolerability failure was defined as treatment-related discontinuation (meeting confirmed virologic withdrawal criteria, treatment-related adverse event, safety stopping criteria, and lack of efficacy). Percentage of participants without virologic failure by Week 24 and Week 48 have been presented. Participants who did not met the protocol defined confirmed virologic withdrawal criteria and are ongoing in the study, or who had discontinued for non-treatment related reasons were censored.
Measured: Week 24 and Week 48
Time to Viral Suppression at Week 48
Viral suppression was defined as HIV-1 RNA <50 c/mL. Time to viral suppression was analyzed and median and interquartile range has been presented.
Measured: Week 48
Change From Baseline in Helper-inducer T-lymphocyte Having Surface Antigen Cluster of Differentiation (CD4+) Cell Count at Weeks 24 and 48
Blood was collected and CD4+ cell count assessment was carried out at indicated time points to evaluate the immunological activity of DTG compared to LPV/RTV. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-dose visit value minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 24 and Week 48
Number of Participants With Disease Progression-Randomized + Continuation Phase
Disease progression included HIV-associated conditions, acquired immune deficiency syndrome (AIDS) and death. Number of participants with disease progression to Centers for Disease Control and Prevention (CDC) class C or death have been presented.
Measured: Up to Week 348
Number of Participants With Treatment-emergent Genotypic Resistance-Randomized Phase
Number of participants, who met confirmed virologic withdrawal (CVW) criteria with paired Baseline and time of CVW resistance data with treatment emergent genotypic resistance to Integrase strand transfer inhibitor (INSTI), NRTI, Protease inhibitor (PI) were summarized. Viral Genotypic Population comprised of all participants in the ITT-E population with available On-treatment genotypic resistance data at the time confirmed virologic withdrawal criterion was met during Randomized Phase.
Measured: Up to Week 52
Number of Participants With Treatment-emergent Genotypic Resistance-Continuation Phase
Number of participants, who met confirmed virologic withdrawal criteria with paired Baseline and time of CVW resistance data, with treatment emergent genotypic resistance to Integrase strand transfer inhibitor (INSTI), NRTI, Protease inhibitor (PI) were summarized. Analysis was performed on Viral Genotypic Continuation Population which comprised all participants in the ITT-E- Continuation Population with available on-treatment genotypic resistance data in the Continuation Phase.
Measured: Up to Week 295
Number of Participants With Fold Change in Treatment-emergent Phenotypic Resistance From Baseline-Randomized Phase
Number of participants with fold change in treatment-emergent phenotypic resistance from Baseline to DTG, LPV/RTV was counted to assess the development of viral resistance. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-dose visit value minus Baseline value. Change in grade 0 to >2 from Baseline is presented. Analysis was performed on viral phenotypic Population, which comprised of all participants in the ITT-E Population with available On-treatment phenotypic resistance data at the time confirmed virologic withdrawal criterion is met during Randomized Phase.
Measured: Baseline (Day 1, Pre-dose) and up to Week 52
Number of Participants With Fold Change in Treatment-emergent Phenotypic Resistance From Baseline-Continuation Phase
Number of participants with fold change in treatment-emergent phenotypic resistance from Baseline to DTG was counted to assess the development of viral resistance. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-dose visit value minus Baseline value. Change in grade 0 to >2 from Baseline is presented. Analysis was performed on Viral Phenotypic Continuation Population which comprises all participants in the ITT-E- Continuation Population with available on-treatment phenotypic resistance data in the Continuation Phase.
Measured: Baseline (Day 1, Pre-dose) and up to Week 295
Number of Participants With Non-serious Adverse Events (AEs) With >=2% Frequency Threshold and Serious Adverse Events (SAEs)-Randomized Phase
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, other situations as per medical or scientific judgment and is associated with liver injury or impaired liver function. Safety Population was used which comprised of all participants who received at least one dose of study treatment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Measured: Up to Week 52
Number of Participants With Non-serious AEs With >=2% Frequency Threshold and SAEs-Continuation Phase
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, other situations as per medical or scientific judgment and is associated with liver injury or impaired liver function. Adverse events which were not Serious were considered as non-serious AEs.
Measured: Up to Week 295
Number of Participants With Non-serious AEs With >=2% Frequency Threshold and SAEs-Randomized + Continuation Phase
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, other situations as per medical or scientific judgment and is associated with liver injury or impaired liver function. Adverse events which were not Serious were considered as non-serious AEs.
Measured: Up to Week 348
Change From Baseline in Glucose, Chloride, Carbon-di-oxide (CO2), Potassium, Phosphate, Sodium, Urea, Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol and Triglycerides
Blood samples were collected from participants to evaluate clinical chemistry parameters including glucose, chloride, carbon-di-oxide (CO2), potassium, phosphate, sodium, urea, cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides. Lipid parameters were evaluated in fasting condition. Change from Baseline in clinical chemistry parameters at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase Values
Blood samples were collected from participants to evaluate clinical chemistry parameters including ALP, ALT, AST and creatine kinase. Change from Baseline in clinical chemistry parameters at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Albumin Values
Blood samples were collected from participants to evaluate clinical chemistry parameter including albumin. Change from Baseline in clinical chemistry parameters at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Creatinine and Bilirubin Values
Blood samples were collected from participants to evaluate clinical chemistry parameters including creatinine and bilirubin. Change from Baseline in clinical chemistry parameters at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Lipase Values
Blood samples were collected from participants to evaluate clinical chemistry parameter including lipase. Change from Baseline in lipase at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Number of Participants With Clinical Chemistry Toxicities -Randomized Phase
Number of participants with clinical chemistry toxicities has been presented. Toxicities were based on the Division of AIDS (DAIDS) grading system. Grade 1=Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Potentially life-threatening. Higher the grade, more severe the symptoms. Lipids and glucose parameters were summarized on fasting data. Data has been reported for clinical chemistry parameters including serum glucose, ALT, Albumin, ALP, AST, Bilirubin, CO2, Creatine kinase, LDL cholesterol calculation, LDL cholesterol direct, Lipase, Phosphate, Potassium, Sodium, Cholesterol, Creatinine and Serum Triglycerides.
Measured: Up to Week 52
Number of Participants With Clinical Chemistry Toxicities-Continuation Phase
Number of participants with clinical chemistry toxicities has been presented. Toxicities were based on the Division of AIDS (DAIDS) grading system. Grade 1=Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Potentially life-threatening. Higher the grade, more severe the symptoms. Lipids and glucose parameters were summarized on fasting data. Data has been reported for clinical chemistry parameters including serum glucose, ALT, Albumin, ALP, AST, Bilirubin, CO2, Creatine kinase, LDL cholesterol calculation, LDL cholesterol direct, Lipase, Phosphate, Potassium, Sodium, Cholesterol, Creatinine and Serum Triglycerides.
Measured: Up to Week 295
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes
Blood samples were collected from participants to evaluate clinical hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes. Change from Baseline in clinical hematology parameters at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Hematocrit Values
Blood samples were collected from participants to evaluate clinical hematology parameter including hematocrit. Change from Baseline in hematocrit values at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and and Week 52
Change From Baseline in Hemoglobin Values
Blood samples were collected from participants to evaluate clinical hematology parameter including hemoglobin. Change from Baseline in hemoglobin values at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Mean Corpuscular Volume (MCV)
Blood samples were collected from participants to evaluate clinical hematology parameter including MCV. Change from Baseline in MCV values at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and and Week 52
Change From Baseline in Erythrocyte Values
Blood samples were collected from participants to evaluate clinical hematology parameter including erythrocyte. Change from Baseline in erythrocyte values at Weeks 4, 8, 16, 24, 36, 48, 52 are presented. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and up to Week 52
Number of Participants With Hematology Toxicities -Randomized Phase
Number of participants with hematology toxicities has been presented. Toxicities were based on the Division of AIDS (DAIDS) grading system. Grade 1=Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Potentially life-threatening. Higher the grade, more severe the symptoms. Data has been reported for hematology parameters including Hemoglobin, Leukocytes, Neutrophils and Platelets.
Measured: Up to Week 52
Number of Participants With Hematology Toxicities-Continuation Phase
Number of participants with hematology toxicities has been presented. Toxicities were based on the Division of AIDS (DAIDS) grading system. Grade 1=Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Potentially life-threatening. Higher the grade, more severe the symptoms. Data has been reported for hematology parameters including Hemoglobin, Leukocytes, Neutrophils and Platelets.
Measured: Up to Week 295
Number of Participants Who Discontinued Treatment Due to AEs-Randomized Phase
Number of participants who discontinued study treatment due to AEs or SAEs were summarized.
Measured: Up to Week 52
Number of Participants Who Discontinued Treatment Due to AEs-Continuation Phase
Number of participants who discontinued study treatment due to AEs were summarized.
Measured: Up to Week 295
Change From Baseline in Fasting LDL Cholesterol at Week 24 and Week 48
Blood samples were collected from participants in fasting state to evaluate LDL cholesterol. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Analysis was performed using multiple imputation with missing at random assumption. Only participants available at the time of evaluation were analyzed.
Measured: Baseline (Day 1, Pre-dose), Week 24 and Week 48
Change From Baseline in Fasting Total Cholesterol/HDL Cholesterol Ratio
Blood samples were collected from participants in fasting state to evaluate total cholesterol/HDL cholesterol ratio. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Only participants available at the time of evaluation were analyzed. Analysis was performed using multiple imputation with missing at random assumption.
Measured: Baseline (Day 1, Pre-dose), Week 24 and Week 48
Number of Participants With Maximum Post-Baseline Emergent Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol
Blood samples were collected from participants in fasting state at indicated time-points to evaluate LDL cholesterol. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Number of participants who experienced maximum grade 2 or greater toxicity post-Baseline in fasting LDL cholesterol was summarized. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Higher the grade, more severe the symptoms.
Measured: Up to Week 48
Number of Participants With Maximum Post-Baseline Emergent Grade 2 or Greater Drug-related Diarrhea
Number of participants who experienced maximum grade 2 or greater toxicity post-Baseline in drug-related diarrhea was summarized. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. Participants were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening. Higher the grade, more severe the symptoms.
Measured: Week 24 and Week 48
Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Score
The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea and Constipation. The scale ranges from 1= no discomfort to 7= very severe discomfort for each symptom cluster. Higher scores show greater severity of symptoms. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. The analysis was performed using Last Observation Carried Forward (LOCF) dataset. In the LOCF dataset, missing values were carried forward from the previous, non-missing available on-treatment assessment.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 24, Week 48
Change From Baseline in Treatment Satisfaction, Using the HIV-Treatment Satisfaction Questionnaire (HIVTSQ) Score
The HIVTSQ is a self-reported scales that measure overall satisfaction with treatment. The score ranges from 0-10. The higher the score, the greater the improvement in treatment satisfaction as compared to the past few weeks. A smaller score represents a decline in treatment satisfaction compared to the past few weeks. Baseline was defined as the latest pre-dose assessment value. Change from Baseline was calculated as post-Baseline visit values minus Baseline value. The analysis was performed using LOCF dataset. In the LOCF dataset, missing values were carried forward from the previous, non-missing available on-treatment assessment.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 24, Week 48
Number of Participants Showing Adherence With Treatment, Using the Morisky 8-Item Medication Adherence Scale (MMAS-8)
Treatment compliance was evaluated through MMAS-8. It is an eight-item self-reported measure of medication-taking behavior. The score ranges from 0-8 where scores of 8 indicate high or near perfect adherence, and scores of less than 6 indicate poor or inadequate adherence on the MMAS-8 scale. Number of participants showing low, medium and high adherence to treatment are presented. Low adherence is a score 0-5.75, medium adherence is a score of 6-7.75 and high adherence is a score of 8. The analysis was performed using LOCF dataset. In the LOCF dataset, missing values were carried forward from the previous, non-missing available on-treatment assessment.
Measured: Baseline (Day 1, Pre-dose), Week 4, Week 24 and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study start11 Dec 2014
- Primary completion2 Aug 2017
- Study completion14 Feb 2022
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 (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 627 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227238
- Sponsor's protocol ID
- 200304
- Other IDs
- 2014-001057-17, 2014
- Status last verified
- Jan 2023
- First submitted
- 25 Aug 2014
- Last updated
- 13 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on ViiV's data sharing criteria can be found at: https://viivhealthcare.com/about-viiv/corporate-ethics-compliance/commitment-to-data-transparency/
Publications
Aboud M, Kaplan R, Lombaard J, Zhang F, Hidalgo JA, Mamedova E, Losso MH, Chetchotisakd P, Brites C, Sievers J, Brown D, Hopking J, Underwood M, Nascimento MC, Punekar Y, Gartland M, Smith K. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Lancet Infect Dis. 2019 Mar;19(3):253-264. doi: 10.1016/S1473-3099(19)30036-2. Epub 2019 Feb 4.
PubMed 30732940Underwood M, Horton J, Nangle K, Hopking J, Smith K, Aboud M, Wynne B, Sievers J, Stewart EL, Wang R. Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0164321. doi: 10.1128/AAC.01643-21. Epub 2021 Oct 25.
PubMed 34694877
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b, Randomized, Open-label Study of the Antiviral Activity and Safety of Dolutegravir Compared to Lopinavir/Ritonavir Both Administered With Dual Nucleoside Reverse Transcriptase Inhibitor Therapy in HIV-1 Infected Adult Subjects With Treatment Failure on First Line Therapy
- ClinicalTrials.gov ID
- NCT02227238
- Acronym / sponsor ID
- 200304
- Conditions
- HIV Infections
- Keywords
- integrase inhibitor, non-inferiority, dolutegravir, lopinavir/ritonavir, second-line treatment, HIV-1, antiretroviral therapy-experienced
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 627 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 11 Dec 2014 (actual)
- Primary completion
- 2 Aug 2017 (actual)
- Study completion
- 14 Feb 2022 (actual)
- First posted
- 28 Aug 2014 (estimated)
- Results
- Posted 12 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
For treatment of human immunodeficiency virus type 1(HIV-1), publicly funded programmes tend to follow World Health Organization (WHO) guidelines to use a non-nucleoside reverse transcriptase inhibitor (NNRTI) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) for first-line antiretroviral therapy (ART); however, there is a need for further data on the best treatment options for people with HIV-1 who have virological failure with this first-line regimen. The number of patients failing on their first-line regimen is increasing thereby requiring a switch to second-line treatment to reduce accumulation of drug-resistance mutations, disease progression, HIV transmission, and death. WHO guidelines recommend second-line antiretroviral therapy for adults consisting of two NRTIs + a ritonavir-boosted protease inhibitor (PI); atazanavir (ATV) plus ritonavir (RTV) or lopinavir (LPV)/RTV are the preferred boosted PI options. This study is conducted to demonstrate non-inferior antiviral activity at 48 weeks of a dolutegravir (DTG) containing regimen compared to a WHO-recommended standard of care regimen for second line treatment, LPV/RTV + two NRTIs, in HIV-1 infected patients failing first line therapy. This study comprises of a Screening Phase (approximately 28 to 42 days), a Randomized Phase (Day 1 to Week 48 plus a 4-week treatment extension), and a Continuation Phase. Approximately 612 subjects will be randomized 1:1 to receive DTG 50 milligram (mg) once daily or LPV/RTV (800/200 mg once daily or 400/100 mg twice daily, in accordance with investigator decision and local label), each added to an investigator selected background regimen of two NRTIs at least one of which needs to be fully active based on viral resistance testing at Screening. Subjects randomized to the LPV/RTV arm will either (i) continue receiving LPV/RTV and complete the study after the 4-week treatment extension at Week 52, or (ii) switch to the DTG arm prior to study completion at Week 52 and continue to have access to DTG in the Continuation Phase. Subjects randomized to receive DTG who successfully complete 52 weeks of treatment and subjects originally randomized to receive LPV/RTV but switched to DTG prior to Week 52 will continue to have access to DTG until it is either locally approved and commercial supplies are available to patients or the patient no longer derives clinical benefit, or the patient meets a protocol-defined reason for discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DTG arm | Experimental | Drug: DTG, Drug: Two NRTIsSubjects will receive one oral tablet of 50 mg DTG once daily plus two NRTIs selected by the investigator |
| LPV/RTV arm | Active comparator | Drug: LPV/RTV, Drug: Two NRTIsSubjects will receive four oral tablets of200/50 mg LPV/RTV once daily or two oral tablets of 200/50 mg LPV/RTV twice daily plus two NRTIs selected by the investigator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HIV-1 infected subjects >=18 years of age.
- A female subject may be eligible to enter and participate in the study if she:
- is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, is of child-bearing potential, with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the protocol-defined methods of contraception to avoid pregnancy throughout the study and for at least 2 weeks after discontinuation of all study medication.
- HIV-1 infection as documented by HIV-1 RNA >=400 c/mL at Screening.
- Subject has been on a first-line treatment regimen consisting of an NNRTI plus two NRTIs for at least 6 months and is currently experiencing virologic failure to this first-line regimen defined as two consecutive (>=7 days apart) HIV-1 RNA results of >=400 c/mL.
Key exclusion criteria (17 listed)
- Women who are breastfeeding.
- Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic or current CD4+ cell levels <200 cells per cubic millimeter
- Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Anticipated need for hepatitis C virus (HCV) therapy during the Randomized Phase of the study.
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 |
|---|---|---|
| DTGDTG is supplied as 50 mg tablets | Drug | DTG arm |
| LPV/RTVLPV/RTV is supplied as the LPV/RTV oral tablet, which contains 200 mg of LPV and 50 mg of RTV | Drug | LPV/RTV arm |
| Two NRTIsInvestigators will choose a dual NRTI background regimen for each subject . In consultation with the medical monitor, 3TC may be added as a third NRTI to a dual-NRTI background regimen in subjects with chronic HBV infection and evidence of HIV resistance to 3TC | Drug | DTG arm, LPV/RTV arm |
Primary outcome
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <50 Copies Per Milliliter (c/mL) at Week 48
Time frame: Week 48
Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior activity of DTG plus 2 NRTI's compared to LPV/RTV plus 2 NRTI's. Analysis was performed on Intent-to-treat exposed (ITT-E) Population, which comprised of all randomized participants who received at least one dose of study medication. Percentage values are rounded off.
36 secondary outcomes
Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24
Time frame: Week 24
Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Weeks 24 and 48
Time frame: Week 24 and Week 48
Percentage of Participants Without Virologic or Tolerability Failure at Week 24 and Week 48
Time frame: Week 24 and Week 48
Time to Viral Suppression at Week 48
Time frame: Week 48
Change From Baseline in Helper-inducer T-lymphocyte Having Surface Antigen Cluster of Differentiation (CD4+) Cell Count at Weeks 24 and 48
Time frame: Baseline (Day 1, Pre-dose), Week 24 and Week 48
Number of Participants With Disease Progression-Randomized + Continuation Phase
Time frame: Up to Week 348
Number of Participants With Treatment-emergent Genotypic Resistance-Randomized Phase
Time frame: Up to Week 52
Number of Participants With Treatment-emergent Genotypic Resistance-Continuation Phase
Time frame: Up to Week 295
Number of Participants With Fold Change in Treatment-emergent Phenotypic Resistance From Baseline-Randomized Phase
Time frame: Baseline (Day 1, Pre-dose) and up to Week 52
Number of Participants With Fold Change in Treatment-emergent Phenotypic Resistance From Baseline-Continuation Phase
Time frame: Baseline (Day 1, Pre-dose) and up to Week 295
Number of Participants With Non-serious Adverse Events (AEs) With >=2% Frequency Threshold and Serious Adverse Events (SAEs)-Randomized Phase
Time frame: Up to Week 52
Number of Participants With Non-serious AEs With >=2% Frequency Threshold and SAEs-Continuation Phase
Time frame: Up to Week 295
Number of Participants With Non-serious AEs With >=2% Frequency Threshold and SAEs-Randomized + Continuation Phase
Time frame: Up to Week 348
Change From Baseline in Glucose, Chloride, Carbon-di-oxide (CO2), Potassium, Phosphate, Sodium, Urea, Cholesterol, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol and Triglycerides
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Albumin Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Creatinine and Bilirubin Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Lipase Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Number of Participants With Clinical Chemistry Toxicities -Randomized Phase
Time frame: Up to Week 52
Number of Participants With Clinical Chemistry Toxicities-Continuation Phase
Time frame: Up to Week 295
Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Hematocrit Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and and Week 52
Change From Baseline in Hemoglobin Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and Week 52
Change From Baseline in Mean Corpuscular Volume (MCV)
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and and Week 52
Change From Baseline in Erythrocyte Values
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 8, Week 16, Week 24, Week 36, Week 48 and up to Week 52
Number of Participants With Hematology Toxicities -Randomized Phase
Time frame: Up to Week 52
Number of Participants With Hematology Toxicities-Continuation Phase
Time frame: Up to Week 295
Number of Participants Who Discontinued Treatment Due to AEs-Randomized Phase
Time frame: Up to Week 52
Number of Participants Who Discontinued Treatment Due to AEs-Continuation Phase
Time frame: Up to Week 295
Change From Baseline in Fasting LDL Cholesterol at Week 24 and Week 48
Time frame: Baseline (Day 1, Pre-dose), Week 24 and Week 48
Change From Baseline in Fasting Total Cholesterol/HDL Cholesterol Ratio
Time frame: Baseline (Day 1, Pre-dose), Week 24 and Week 48
Number of Participants With Maximum Post-Baseline Emergent Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol
Time frame: Up to Week 48
Number of Participants With Maximum Post-Baseline Emergent Grade 2 or Greater Drug-related Diarrhea
Time frame: Week 24 and Week 48
Change From Baseline in Gastrointestinal Symptom Rating Scale (GSRS) Score
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 24, Week 48
Change From Baseline in Treatment Satisfaction, Using the HIV-Treatment Satisfaction Questionnaire (HIVTSQ) Score
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 24, Week 48
Number of Participants Showing Adherence With Treatment, Using the Morisky 8-Item Medication Adherence Scale (MMAS-8)
Time frame: Baseline (Day 1, Pre-dose), Week 4, Week 24 and Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30732940Aboud M, Kaplan R, Lombaard J, Zhang F, Hidalgo JA, Mamedova E, Losso MH, Chetchotisakd P, Brites C, Sievers J, Brown D, Hopking J, Underwood M, Nascimento MC, Punekar Y, Gartland M, Smith K. Dolutegravir versus ritonavir-boosted lopinavir both with dual nucleoside reverse transcriptase inhibitor therapy in adults with HIV-1 infection in whom first-line therapy has failed (DAWNING): an open-label, non-inferiority, phase 3b trial. Lancet Infect Dis. 2019 Mar;19(3):253-264. doi: 10.1016/S1473-3099(19)30036-2. Epub 2019 Feb 4.
- Background: PubMed 34694877Underwood M, Horton J, Nangle K, Hopking J, Smith K, Aboud M, Wynne B, Sievers J, Stewart EL, Wang R. Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0164321. doi: 10.1128/AAC.01643-21. Epub 2021 Oct 25.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on ViiV's data sharing criteria can be found at: https://viivhealthcare.com/about-viiv/corporate-ethics-compliance/commitment-to-data-transparency/
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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.
GSK Clinical Trials study director
ViiV Healthcare
59 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing DTG, LPV/RTV and Two NRTIs in people with HIV Infections, run by ViiV Healthcare at 59 sites in 13 countries.
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 8 inclusion and 17 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 13 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in Russia, Argentina, Romania, South Africa, Thailand and 8 more countries. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2019). 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?
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <50 Copies Per Milliliter (c/mL) at Week 48 (time frame: Week 48). 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 NCT02227238, which also lists 2 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 13 Mar 2023.