HIV I Infection
Conditions
Keywords
switch study, dovato, biktarvy
Brief summary
Phase 4, randomized, open-label study to evaluate the efficacy, safety and tolerability of switching virologically suppressed adults living with HIV on bictegravir/tenofovir alafenamide/emtricitabine to dolutegravir/lamivudine
Detailed description
Randomized, open-label, active-controlled study of virologically suppressed participants living with HIV Participants who provide written informed consent and meet all the eligibility criteria will be randomized in a 2:1 ratio to one of the following 2 treatment groups: Treatment Group 1 (n=148): FDC of DTG/3TC (50mg/300mg) administered orally, once daily (QD), without regard to food. Treatment Group 2 (n=74): Stay on baseline regimen consisting of FDC of B/F/TAF (50mg/200mg/ 25mg) (taken as prescribed) without regard to food. Randomization will be stratified by gender and race at entry given that this study aims to enroll at least 30% of participants who are female and African American. All participants will be responsible for using their insurance plan to obtain coverage for DTG/3TC and or B/F/TAF, in addition to any labs required by the study. This expectation is clearly outlined in the informed consent. The study team will work with participants to minimize their co-pays for study medications and labs through the use of manufacturer and other external assistance programs. Study duration will be 48 weeks. Number of participants planned: Approximately 222 participants Target Population: HIV-1 infected adult participants who are virologically suppressed (HIV-1 RNA\<50 copies/mL) on FDC of B/F/TAF (50mg/200mg/ 25mg) ≥ 3 months prior to screening
Interventions
DRUGBictegravir / Emtricitabine / Tenofovir Alafenamide Pill
Active comparator
Experimental
Sponsors
ViiV Healthcare
Charlotte-Paige Rolle, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, open-label, active-controlled study of virologically suppressed participants living with HIV
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- 1. Aged 18 years or older at the time of signing the informed consent TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 2. HIV-1 infected men or women. 3. Must have a stable form of insurance that is expected to continue without significant changes for at least 48 weeks 4. Documented evidence of at least two plasma HIV-1 RNA measurements \<50 c/mL at least 3 months apart prior to Day 1 (the screening HIV-1 RNA can count as the second measurement) 5. Plasma HIV-1 RNA \<50 c/mL at Screening. 6. Must be on uninterrupted B/F/TAF for at least 3 months prior to screening SEX 7. Male or female A female subject is eligible to participate if she is not pregnant \[as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at Day 1/Randomization (a local serum hCG test at Randomization is allowed if it can be done, and results obtained, within 24 hours prior to randomization)\], not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential defined as: * Pre-menopausal females with one of the following: o Documented tubal ligation * Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion * Hysterectomy * Documented Bilateral Oophorectomy * Post-menopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. 2. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) (see Appendix 2) from 30 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. All subjects participating in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner. INFORMED CONSENT 8\. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible subjects must sign a written Informed Consent Form before any protocol-specified assessments are conducted b.
Exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure is to Evaluate the Efficacy of Switching From B/F/TAF to DTG/3TC Versus Continuing B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | 48 weeks | percentage with HIV-1 RNA ≥50 copies/mL at Week 48 in each treatment arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA<50 Copies/mL at Week 48 | 48 weeks | percentage with HIV-1 RNA\<50 copies/mL at Weeks 12, 24 and 48 in each treatment arm |
| The Secondary Outcome Measure is to Measure the Incidence and Severity of Grade 2-5 Drug-related Adverse Events and Laboratory Abnormalities (Graded Using DAIDs Grading Scale) Through 48 Weeks | 48 weeks | Grade 2-5 drug-related AEs and lab abnormalities graded using DAIDS grading scale |
| The Secondary Outcome Measure is to Evaluate the Proportion of Participants That Discontinue Treatment Through 48 Weeks in Each Treatment Arm and Reasons for Discontinuation | 48 weeks | Number of participants who discontinue study treatment and reasons for discontinuation |
| The Secondary Outcome Measure is to Evaluate the Effects of DTG/3TC Once Daily on Fasting Total Cholesterol Over Time Compared to B/F/TAF Through 48 Weeks | 48 weeks | Change from Baseline in fasting total cholesterol at Week 48 |
| The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA≥ 50 Copies/mL at Week 24 | 24 weeks | percentage with HIV-1 RNA ≥50 copies/mL at Week 24 in each treatment arm |
| The Secondary Outcome Measure is to Evaluate Changes in Waist Circumference (Inches) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | 48 weeks | Change from Baseline in waist circumference (measured in inches) at Week 48 |
| The Secondary Outcome Measure is to Evaluate Changes in BMI (kg/m2) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | 48 weeks | Change from Baseline in weight (kg) and height (meters) will be used to assess changes in BMI (kg/m2) measured at Week 48 |
| To Assess the Number of Subjects With Genotypic Mutations Affecting Any Component of the Treatment Regimen Among Subjects Meeting Virologic Rebound Criteria (HIV-1 RNA≥50 Copies/mL X2) Using HIV Genotypic and ARCHIVE HIV-DNA Testing | 48 weeks | to measure the incidence of observed genotypic resistance to ARVs for subjects meeting Virologic Rebound Criteria |
| The Secondary Outcome Measure is to Evaluate Changes in Weight (kg) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | 48 weeks | Change from Baseline in weight (kg) measured at Week 48 |
Countries
United States
Participant flow
Recruitment details
The first participant was screened on 10/5/2020 and the last participant's Week 48 visit was on 8/3/2023. Of 235 screened, 222 were enrolled and randomized to switch to DTG/3TC (n=149) or continue B/F/TAF (n=73), 222 received study treatment (ITT-E)
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group 1 Treatment Group 1 (n=149): FDC of DTG/3TC (50mg/300mg) administered orally, once daily (QD), without regard to food.
Dolutegravir / Lamivudine Pill: Experimental | 149 |
| Treatment Group 2 Treatment Group 2 (n=74): Stay on baseline regimen consisting of FDC of B/F/TAF (50mg/200mg/ 25mg) (taken as prescribed) without regard to food.
Bictegravir / Emtricitabine / Tenofovir Alafenamide Pill: Active comparator | 73 |
| Total | 222 |
Baseline characteristics
| Characteristic | Treatment Group 1 | Treatment Group 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 11 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 140 Participants | 62 Participants | 202 Participants |
| Race/Ethnicity, Customized Black/African American | 44 Participants | 18 Participants | 62 Participants |
| Race/Ethnicity, Customized Caucasian | 102 Participants | 54 Participants | 156 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 149 Participants | 73 Participants | 222 Participants |
| Sex: Female, Male Female | 24 Participants | 12 Participants | 36 Participants |
| Sex: Female, Male Male | 125 Participants | 61 Participants | 186 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 149 | 0 / 73 |
| other Total, other adverse events | 14 / 149 | 1 / 73 |
| serious Total, serious adverse events | 12 / 149 | 4 / 73 |
Outcome results
Primary
The Primary Outcome Measure is to Evaluate the Efficacy of Switching From B/F/TAF to DTG/3TC Versus Continuing B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
percentage with HIV-1 RNA ≥50 copies/mL at Week 48 in each treatment arm
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | The Primary Outcome Measure is to Evaluate the Efficacy of Switching From B/F/TAF to DTG/3TC Versus Continuing B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | 6 Participants |
| Treatment Group 2 | The Primary Outcome Measure is to Evaluate the Efficacy of Switching From B/F/TAF to DTG/3TC Versus Continuing B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48 | 5 Participants |
Secondary
The Secondary Outcome Measure is to Evaluate Changes in BMI (kg/m2) in Those Treated With DTG/3TC vs. B/F/TAF Over Time
Change from Baseline in weight (kg) and height (meters) will be used to assess changes in BMI (kg/m2) measured at Week 48
Time frame: 48 weeks
Population: change in BMI over 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate Changes in BMI (kg/m2) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | -0.6 kg/m2 |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate Changes in BMI (kg/m2) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | -0.1 kg/m2 |
Secondary
The Secondary Outcome Measure is to Evaluate Changes in Waist Circumference (Inches) in Those Treated With DTG/3TC vs. B/F/TAF Over Time
Change from Baseline in waist circumference (measured in inches) at Week 48
Time frame: 48 weeks
Population: mean change from baseline in weight circumference
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate Changes in Waist Circumference (Inches) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | -0.9 inches |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate Changes in Waist Circumference (Inches) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | -0.7 inches |
Secondary
The Secondary Outcome Measure is to Evaluate Changes in Weight (kg) in Those Treated With DTG/3TC vs. B/F/TAF Over Time
Change from Baseline in weight (kg) measured at Week 48
Time frame: 48 weeks
Population: mean change in weight at 48 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate Changes in Weight (kg) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | -1 kg |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate Changes in Weight (kg) in Those Treated With DTG/3TC vs. B/F/TAF Over Time | 0.2 kg |
Secondary
The Secondary Outcome Measure is to Evaluate the Effects of DTG/3TC Once Daily on Fasting Total Cholesterol Over Time Compared to B/F/TAF Through 48 Weeks
Change from Baseline in fasting total cholesterol at Week 48
Time frame: 48 weeks
Population: change in total cholesterol
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate the Effects of DTG/3TC Once Daily on Fasting Total Cholesterol Over Time Compared to B/F/TAF Through 48 Weeks | -2.3 mg/dL |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate the Effects of DTG/3TC Once Daily on Fasting Total Cholesterol Over Time Compared to B/F/TAF Through 48 Weeks | 3.3 mg/dL |
Secondary
The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA≥ 50 Copies/mL at Week 24
percentage with HIV-1 RNA ≥50 copies/mL at Week 24 in each treatment arm
Time frame: 24 weeks
Population: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA≥ 50 Copies/mL at Week 24 | 3 Participants |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA≥ 50 Copies/mL at Week 24 | 3 Participants |
Secondary
The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA<50 Copies/mL at Week 48
percentage with HIV-1 RNA\<50 copies/mL at Weeks 12, 24 and 48 in each treatment arm
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA<50 Copies/mL at Week 48 | 127 Participants |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate the Efficacy of Switching to DTG/3TC From B/F/TAF as Determined by the Proportion of Participants With HIV-1 RNA<50 Copies/mL at Week 48 | 59 Participants |
Secondary
The Secondary Outcome Measure is to Evaluate the Proportion of Participants That Discontinue Treatment Through 48 Weeks in Each Treatment Arm and Reasons for Discontinuation
Number of participants who discontinue study treatment and reasons for discontinuation
Time frame: 48 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Evaluate the Proportion of Participants That Discontinue Treatment Through 48 Weeks in Each Treatment Arm and Reasons for Discontinuation | 15 Participants |
| Treatment Group 2 | The Secondary Outcome Measure is to Evaluate the Proportion of Participants That Discontinue Treatment Through 48 Weeks in Each Treatment Arm and Reasons for Discontinuation | 9 Participants |
Secondary
The Secondary Outcome Measure is to Measure the Incidence and Severity of Grade 2-5 Drug-related Adverse Events and Laboratory Abnormalities (Graded Using DAIDs Grading Scale) Through 48 Weeks
Grade 2-5 drug-related AEs and lab abnormalities graded using DAIDS grading scale
Time frame: 48 weeks
Population: overall number of participants experiencing Grade 2-5, drug-related AEs
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | The Secondary Outcome Measure is to Measure the Incidence and Severity of Grade 2-5 Drug-related Adverse Events and Laboratory Abnormalities (Graded Using DAIDs Grading Scale) Through 48 Weeks | 14 Participants |
| Treatment Group 2 | The Secondary Outcome Measure is to Measure the Incidence and Severity of Grade 2-5 Drug-related Adverse Events and Laboratory Abnormalities (Graded Using DAIDs Grading Scale) Through 48 Weeks | 1 Participants |
Secondary
To Assess the Number of Subjects With Genotypic Mutations Affecting Any Component of the Treatment Regimen Among Subjects Meeting Virologic Rebound Criteria (HIV-1 RNA≥50 Copies/mL X2) Using HIV Genotypic and ARCHIVE HIV-DNA Testing
to measure the incidence of observed genotypic resistance to ARVs for subjects meeting Virologic Rebound Criteria
Time frame: 48 weeks
Population: number of participants with treatment-emergent resistance through Week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group 1 | To Assess the Number of Subjects With Genotypic Mutations Affecting Any Component of the Treatment Regimen Among Subjects Meeting Virologic Rebound Criteria (HIV-1 RNA≥50 Copies/mL X2) Using HIV Genotypic and ARCHIVE HIV-DNA Testing | 2 Participants |
| Treatment Group 2 | To Assess the Number of Subjects With Genotypic Mutations Affecting Any Component of the Treatment Regimen Among Subjects Meeting Virologic Rebound Criteria (HIV-1 RNA≥50 Copies/mL X2) Using HIV Genotypic and ARCHIVE HIV-DNA Testing | 1 Participants |