Clinical Trial Results:
An open-label, single arm study to evaluate the week 48 efficacy and safety of a two-drug regimen of dolutegravir/lamivudine (DTG/3TC) as a fixed dose combination (FDC), in antiretroviral therapy (ART)-naive HIV-1-infected adolescents, ≥12 to <18 years of age who weigh at least 25 kg
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Summary
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EudraCT number |
2025-000361-93 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
22 May 2025
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Dec 2025
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First version publication date |
06 Dec 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
205861
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03682848 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Jun 2025
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 May 2025
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The study consists of Screening Phase (up to 28 days prior to the first dose of drug) followed by Treatment Phase (up to 48 weeks). Participants who successfully complete 48 weeks of therapy and who continue to receive benefit from DTG/3TC FDC may enter a 96 weeks study Extension Phase. Study participants who have successfully completed both the Treatment Phase through 48 weeks and the Extension Phase through 144 weeks and continue to receive benefit from this two-drug regimen will continue to receive DTG/3TC FDC in a Continuation Phase (after Week 144) until: DTG and 3TC are both locally approved for use as part of a dual regimen and the single entities of DTG and 3TC are available to participants or the DTG/3TC FDC tablet, if required by local regulations, is locally approved and available (e.g. commercially or through public health services), or the participant no longer derives clinical benefit or the participant meets a protocol-defined reason for discontinuation.
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Protection of trial subjects |
All study activities at the study center were performed by trained clinical staff authorized by the study Investigator. The attendance of the study participants at in-person study visit did not pose risks that extend beyond the risks associated with clinic visits for routine immunization. Considering the measures taken to minimize possible risks to the participants in this study, the potential risks associated with the study interventions and study assessments were balanced by the potential benefits that may be provided to the participants. Study participants were observed for a minimum of 30 minutes after the administration of study interventions with appropriate medical attention available in case of anaphylaxis.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 May 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Kenya: 10
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Country: Number of subjects enrolled |
South Africa: 3
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Country: Number of subjects enrolled |
Thailand: 19
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Worldwide total number of subjects |
32
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
32
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
All participants that were screened were eligible to start the study and receive the study intervention, and were included in the Intent-to-Treat Exposed set. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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DTG/3TC FDC | ||||||||||||||||||
Arm description |
Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 mg) Fixed Dose Combination (FDC) tablets orally once daily. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
DTG + 3TC FDC
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
DTG + 3TC FDC tablets administered once daily.
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Baseline characteristics reporting groups
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Reporting group title |
DTG/3TC FDC
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Reporting group description |
Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 mg) Fixed Dose Combination (FDC) tablets orally once daily. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
DTG/3TC FDC
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Reporting group description |
Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 mg) Fixed Dose Combination (FDC) tablets orally once daily. | ||
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End point title |
Percentage of participants with plasma Human Immunodeficiency Virus type 1 (HIV-1) ribonucleic acid (RNA) less than 50 copies per milliliter (c/mL) at Week 48 [1] | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <50 c/mL was assessed at Week 48 according to the Food and Drug Administration (FDA) snapshot algorithm. Intent To Treat-Exposed (ITT-E) population includes all enrolled participants who received at least one dose of DTG/3TC.
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End point type |
Primary
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End point timeframe |
Week 48
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <200 c/mL at Week 24 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <200 c/mL was assessed at Week 24 according to the FDA snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of participants with adverse events (AEs) and serious adverse events (SAEs) through 144 weeks | ||||||||||
End point description |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Safety population includes participants who have received at least one dose of DTG/3TC.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 96 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <50 c/mL was assessed at Week 96 according to the FDA snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 144 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <50 c/mL was assessed at Week 144 according to the FDA Snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 144
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <200 c/mL at Week 48 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <200 c/mL was assessed at Week 48 according to the FDA snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <200 c/mL at Week 144 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <200 c/mL was assessed at Week 144 according to the FDA snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 144
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <200 c/mL at Week 96 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <200 c/mL was assessed at Week 96 according to the FDA snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 24 | ||||||||
End point description |
Percentage of participants with plasma HIV-1 RNA <50 c/mL was assessed at Week 24 according to the FDA snapshot algorithm. Analysis was performed on the Intent To Treat-Exposed.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of participants with AEs through 144 weeks by severity | ||||||||||||||||
End point description |
The Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria for grading the severity of adult and pediatric adverse events was used to assess severity. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences; Grade 5 - death. A higher grade indicates a greater severity. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of participants with abnormal findings for hematology parameters through 144 weeks | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for analysis of hematology parameters including hemoglobin, leukocytes and neutrophils. The DAIDS criteria for grading the severity of adult and pediatric adverse events was used to assess severity. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of participants with abnormal findings for clinical chemistry parameters through 144 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for analysis of clinical chemistry parameters including potassium, aspartate aminotransferase, creatinine, alanine aminotransferase (ALT), carbon dioxide, alkaline phosphatase, bilirubin, direct bilirubin, sodium, GFR from creatinine adjusted for BSA, calcium, and creatine kinase. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants with abnormal findings for fasting lipids through 144 weeks | ||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Lipid assessments including cholesterol, low density lipoprotein (LDL) cholesterol, LDL Cholesterol Calculation, LDL Cholesterol Direct, and triglycerides were performed. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants with abnormal findings for urinalysis parameters through 144 weeks | ||||||||||||||||||||||||||||||
End point description |
Urine samples were collected from participants for the analysis of urinalysis parameters including urinary glucose, urinary protein, and urine erythrocytes. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of participants who discontinue treatment due to adverse events through 144 weeks | ||||||
End point description |
Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 144 weeks
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| No statistical analyses for this end point | |||||||
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End point title |
Number of participants with adverse events and serious adverse events through 96 weeks | ||||||||||
End point description |
Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 96 weeks
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of participants with severity of adverse events through 96 weeks | ||||||||||||||||
End point description |
AEs were evaluated by the investigator and graded according to the DAIDS toxicity scales as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences; Grade 5 - death. The higher the grade, the more severe the symptoms. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 96 weeks
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of participants with abnormal findings for hematology parameters through 96 weeks | ||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for analysis of hematology parameters including hemoglobin, leukocytes and neutrophils. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 96 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of participants with abnormal findings for clinical chemistry parameters through 96 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for analysis of clinical chemistry parameters including potassium, aspartate aminotransferase, creatinine, alanine aminotransferase, carbon dioxide, alkaline phosphatase, bilirubin, sodium, GFR from creatinine adjusted for BSA, calcium, and creatine kinase. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 96 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants with abnormal findings for fasting lipids through 96 weeks | ||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Lipid assessments including cholesterol, LDL cholesterol, LDL cholesterol calculation, LDL cholesterol direct, and triglycerides were performed. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 96 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants with abnormal findings for urinalysis parameters through 96 weeks | ||||||||||||||||||||||||||||||
End point description |
Urine samples will be collected from participants for the analysis of urinalysis parameters including urinary glucose, urinary protein, and urine erythrocytes. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Up to 96 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Number of participants undergoing viral load monitoring from Week 48 through 144 weeks | ||||||||||||||||||||||||
End point description |
Viral load was defined as plasma HIV-RNA <50 copies per mL. Viral load monitoring of participants was performed from Week 48 through 144 weeks. Analysis was performed on the Safety population.
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End point type |
Secondary
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End point timeframe |
Weeks 48, 60, 72, 84, 96, 108, 120, 132, and 144
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Change from Baseline in cluster of differentiation 4+ (CD4+) cell count at Weeks 24 and 48 | ||||||||||||||
End point description |
Baseline value was defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value.
Analysis was performed on the Intent-To-Treat Exposed. Only those participants with data available at specified time points were analyzed.
N = the number of participants analyzed at the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1) and Weeks 24 and 48
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Change from Baseline in CD8+ cell count at Weeks 24 and 48 | ||||||||||||||
End point description |
Baseline value was defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value.
Analysis was performed on the Intent-To-Treat Exposed. Only those participants with data available at specified time points were analyzed.
N = the number of participants analyzed at the specified timepoints.
|
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End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 24 and 48
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Change from Baseline in ratio of CD4+ and CD8+ at Weeks 24 and 48 | ||||||||||||||
End point description |
Baseline value was defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline was defined as post-dose visit value minus Baseline value.
Analysis was performed on the Intent-To-Treat Exposed. Only those participants with data available at specified time points were analyzed.
N = the number of participants analyzed at the specified timepoints.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Baseline (Day 1) and Weeks 24 and 48
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||
End point title |
Number of participants with disease progression from Week 24 through Week 48 | ||||||||||
End point description |
Participants with disease progression included incidences of HIV-associated conditions, Acquired Immuno Deficiency Syndrome (AIDS) and death. HIV-associated conditions were assessed according to the 2014 HIV infection by Centers for Disease Control and Prevention (CDC) classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC. Analysis was performed on the Safety population.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||
End point title |
Number of participants with severity of adverse events from Week 24 through Week 48 | ||||||||||||||||||||||||||
End point description |
AEs were evaluated by the investigator and graded according to the DAIDS toxicity scales as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences; Grade 5 - death. The higher the grade, the more severe the symptoms. Analysis was performed on the Safety population.
|
||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||
|
|||||||||||||||
End point title |
Number of participants with any adverse events and serious adverse events from Week 24 through Week 48 | ||||||||||||||
End point description |
Analysis was performed on the Safety population.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal findings for hematology parameters from Week 24 through Week 48 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for analysis of hematology parameters including hemoglobin, leukocytes and neutrophils. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal findings for clinical chemistry parameters from Week (W) 24 through Week 48 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Blood samples were collected from participants for analysis of clinical chemistry parameters including potassium, aspartate aminotransferase, creatinine, alanine aminotransferase, carbon dioxide, alkaline phosphatase, bilirubin, sodium, GFR from creatinine adjusted (adj) for BSA, calcium, and creatine kinase. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal findings for fasting lipids from Week 24 through Week 48 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Lipid assessments including cholesterol, LDL cholesterol, LDL cholesterol calculation, LDL cholesterol direct, and triglycerides were performed. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
End point title |
Number of participants with abnormal findings for urinalysis parameters from Week 24 through Week 48 | ||||||||||||||||||||||||||||||||||||||
End point description |
Urine samples will be collected from participants for the analysis of urinalysis parameters including urinary glucose, urinary protein, and urine erythrocytes. Grades were defined based on numeric criteria as follows: Grade 1 - mild; Grade 2 - moderate; Grade 3 - severe or medically significant; Grade 4 - life-threatening consequences. Analysis was performed on the Safety population.
|
||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
|
|||||||||||
End point title |
Number of participants who discontinued treatment due to adverse events from Week 24 through Week 48 | ||||||||||
End point description |
Analysis was performed on the Safety population.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Week 24 and up to Week 48
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||
End point title |
Maximum observed plasma concentration (Cmax) following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Intensive Pharmacokinetic Population includes all participants who received at least 1 dose of DTG/3TC FDC and have evaluable drug concentrations reported, where samples are collected according to the intensive sampling schedule.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Time of maximum observed plasma concentration (Tmax) following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Analysis was performed on the Intensive Pharmacokinetic Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Area under the plasma concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC[0-t]) following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Analysis was performed on the Intensive Pharmacokinetic Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Area under the curve (AUC) over the dosing interval (AUC[0-tau]) following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Analysis was performed on the Intensive Pharmacokinetic Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Apparent terminal half-life (t1/2) following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Analysis was performed on the Intensive Pharmacokinetic Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre-dose, 0.5, 1.0, 1.5, 2, 3, 4, 6, 10, and 24 hours post-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Observed pre-dose plasma concentration following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Analysis was performed on the Intensive Pharmacokinetic Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Pre-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Observed plasma concentration at 24 hours following dosing with DTG and 3TC | ||||||||||||
End point description |
Blood samples were collected on a subset of participants for intensive pharmacokinetic analysis. Analysis was performed on the Intensive Pharmacokinetic Population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
24 hours post-dose at Week 1
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||
End point title |
Number of participants with observed genotypic resistance to DTG and 3TC | ||||||
End point description |
Protocol-defined confirmed virologic withdrawal (CVW) through Week 144 was low with 1 participant meeting CVW criteria. Resistance testing failed, and therefore no genotypic data were available for this participant at the time of virologic failure.
The analysis used the CVW population, comprising ITT-E participants meeting CVW criteria: confirmed virologic non-response (HIV-1 RNA <1 log10 c/mL at/after Week 12 or =200 c/mL at/after Week 24) or confirmed rebound (HIV-1 RNA =200 c/mL after prior suppression <200 c/mL).
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Up to 144 weeks
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Number of participants with observed phenotypic resistance to DTG and 3TC | ||||||
End point description |
Protocol-defined CVW through Week 144 was low with 1 participant meeting CVW criteria. Resistance testing failed, and therefore no phenotypic data were available for this participant at the time of virologic failure.
The analysis used the CVW population.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Up to 144 weeks
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All-Cause mortality, Non-SAEs and SAEs were collected from Day 1 up to Week 144
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
28.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
DTG/3TC FDC
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 (mg) Fixed Dose Combination (FDC) tablets orally once daily through Week 48. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Jun 2018 |
The amendment was developed in order to reinforce the importance of pregnancy avoidance and contraception requirements. |
||
12 Nov 2019 |
The amendment was developed to incorporate a Continuation Phase to enable post study drug provision for eligible participants who may benefit from continued treatment. |
||
20 Nov 2020 |
The amendment was developed to include stepwise instruction, based on severity grade, for confirmatory testing and assessment, and
parameters for temporary holding or permanent discontinuation of study treatment, in order to to clarify and simplify participant management. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
