HIV Infections
Conditions
Brief summary
The purpose of this study is to determine whether the BMS Attachment Inhibitor (BMS-663068) is effective in the treatment of heavily treatment experienced HIV-1 patients with multi-drug resistance.
Interventions
DRUGBMS-663068
BMS-663068
OTHERPlacebo
Placebo
Sponsors
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and non-pregnant women with chronic HIV-1 infection * Antiretroviral-experienced with documented historical or baseline resistance, intolerability, and/or contraindications to antiretrovirals in at least three classes * Failing current antiretroviral regimen with a confirmed plasma HIV-1 RNA ≥ 400 c/mL (first value from Investigator, second from Screening labs) * Must have ≤ 2 classes with at least 1 but no more than 2 fully-active antiretrovirals remaining which can be effectively combined to form a viable new regimen, based on current and/or documented historical resistance testing and tolerability and safety * Able to receive ≥ 1 fully active approved antiretroviral as part of the OBT from Day 9 onwards in the Randomized Cohort * Subjects without any remaining fully active approved antiretroviral may be enrolled in the Non-Randomized Cohort
Exclusion criteria
* Chronic untreated Hepatitis B virus (HBV) (however, patients with chronic treated HBV are eligible) * HIV-2 infection * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 7 x ULN * Alkaline Phosphatase \> 5 x ULN * Bilirubin ≥ 1.5 x Upper limit of normal (ULN) (unless subject is currently on atazanavir and has predominantly unconjugated hyperbilirubinemia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort | Day 1 and Day 8 | Plasma samples were collected for analysis of HIV-1 RNA. Mean change in log10 HIV-1 RNA from Day 1 was estimated using analysis of covariance (ANCOVA) with log10 HIV-1 RNA change from Day 1 at Day 8 as dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 log10 HIV-1 RNA as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. The 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 treatment. Missing HIV-1 RNA values at Day 8 were imputed using (a) Day 1 Observation Carried Forward (D1OCF) for participants without a value during blinded treatment (i.e, imputing a zero change from Day 1) or (b) Last Observation Carried Forward (LOCF) for participants with an early value during blinded treatment before the Day 8 analysis visit window. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort | At Weeks 24, 48 and 96 | The durability of response (that is, the number of participants achieving HIV-1 RNA \<40 c/mL) at Weeks 24, 48 and 96 of open-label fostemsavir plus OBT in the Randomized Cohort was assessed using the Food and Drug Administration (FDA) snapshot algorithm in which participants without HIV-1 RNA at Weeks 24, 48 and 96 or those who changed OBT due to lack of efficacy through Weeks 24, 48 and 96 were counted as failures. The percentage of participants in the Randomized Cohort who achieved virologic success (HIV-1 RNA \<40 c/mL) at Weeks 24, 48 and 96 is presented along with 95% Wilson confidence interval. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan. |
| Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort | Up to Week 96 analysis cut-off date | An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; an important medical event that may jeopardize the participant or require intervention. Number of participants with on-treatment SAEs and AEs leading to withdrawal of study treatment is presented. SAEs and AELDs were collected in Safety Population which comprised of all participants who received at least one dose of study treatment. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan. |
| Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Baseline and up to Week 96 analysis cut-off date | Laboratory toxicities were graded for severity according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with clinical chemistry toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan. |
| Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Baseline and up to Week 96 analysis cut-off date | Laboratory toxicities were graded for severity according to the DAIDS grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with hematology toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan. |
| Number of Participants With Centers for Disease Control (CDC) Class C Events-Randomized Cohort | Up to Week 96 analysis cut-off date | Disease progression during open label fostemsavir plus OBT was assessed based on the occurrence of new AIDS defining events (CDC Class C events) or death. The number of participants with on-treatment CDC Class C AIDS events is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan. |
| Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort | Day 1 and Day 8 | CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell counts from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an in-dependent variable, and Day 1 CD4+ cell count as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (i.e., imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window. |
| Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort | Day 1 and Day 8 | The percentage of participants in the Randomized Cohort with HIV-1 RNA decreases from Day 1 that exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8 was determined by comparing HIV-1 RNA Day 1 measurement of each participant to their Day 8 measurement. This was an ITT analysis that classified participants without HIV-1 RNA at Day 1 or Day 8 as failures. The percentage of responders along with 95% confidence interval based on Wilson score is presented. |
| Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96 | Blood samples were collected for the analysis of HIV-1 RNA. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan. |
| Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96 | CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. |
| Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96 | Percentage CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. |
| Number of Participants With Treatment-emergent Viral Genotypic Substitution of Interest in the GP160 Domain as a Measure of Genotypic Resistance-Randomized Cohort | Week 96 | Plasma samples were collected for emergent drug resistance testing. The number of participants with emergent viral genotypic substitutions of interest in the GP160 domain was identified by the next-generation sequencing (NGS) assay. Protocol defined virologic failure (PDVF) through Week 96 Population comprised of all participants with available phenotypic and genotypic resistance data meeting at the time protocol defined virologic failure (PDVF) was met. The criteria for PDVF was a) Confirmed, or last available prior to discontinuation, HIV-1 RNA \>=400 c/mL at any time after prior confirmed suppression to \<400 c/mL prior to Week 24 or Confirmed, or last available prior to discontinuation, \> 1 log10 c/mL increase in HIV-1 RNA at any time above nadir level where nadir is \>=40 c/mL prior to Week 24. b) Confirmed, or last available prior to discontinuation, HIV-1 RNA \>=400 c/mL at or after Week 24. |
| Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | Week 96 | The phenotypic resistance to a drug is defined in terms of a fold change (FC) in IC50s, i.e., the ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of a reference strain (wild type control). FCR was calculated as FC at PDVF divided by Baseline FC. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. FCR\<1 indicates that FC is smaller on-treatment than at Baseline. FCR \>3 indicates that on-treatment FC is 3 times greater than it was at Baseline. |
| Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort | Day 1 and Day 8 | CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count percentage from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell count percentage from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 CD4+ cell count percentage as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (ie, imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Colombia, France, Germany, Greece, Ireland, Italy, Mexico, Netherlands, Peru, Poland, Portugal, Puerto Rico, Romania, Russia, South Africa, Spain, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This was a 2 cohort Phase 3 study conducted in heavily treatment experienced (HTE) participants infected with multi-drug resistant human immunodeficiency virus (HIV)-1. Participants were assigned to either the Randomized Cohort (participants received either fostemsavir or placebo) or Non-randomized Cohort (all participants received fostemsavir).
Pre-assignment details
A total of 731 participants were screened, of which 371 were included in either Randomized Cohort or Non-randomized Cohort and received at least one dose of study treatment. The results presented are based on Week 96 interim analysis. Data collection is still on-going and additional results will be provided after study completion.
Participants by arm
| Arm | Count |
|---|---|
| Randomized Cohort-Placebo Eligible participants in the Randomized Cohort had one to two fully active antiretrovirals remaining at Baseline. Participants received placebo twice daily (BID) along with their currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants received fostemsavir 600 mg BID with an optimized background therapy (OBT). | 69 |
| Randomized Cohort-fostemsavir 600 mg BID Eligible participants in the Randomized Cohort had one to two fully active antiretrovirals remaining at Baseline. Participants received fostemsavir 600 milligram (mg) BID along with currently failing antiretroviral regimen for 8 days during the randomized, double-blind period. During the open-label period, all participants continued to receive fostemsavir 600 mg BID with an OBT. | 203 |
| Non-randomized Cohort-fostemsavir 600 mg BID-Open Label Period Eligible participants in the Non-randomized Cohort had zero remaining fully active and approved antiretroviral regimens at Baseline. Participants received fostemsavir 600 mg BID in combination with OBT. | 99 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-blind Period-Up to 8 Days | Adverse Event | 0 | 2 | 0 |
| Double-blind Period-Up to 8 Days | Death | 1 | 0 | 0 |
| Double-blind Period-Up to 8 Days | Lost to Follow-up | 0 | 1 | 0 |
| Double-blind Period-Up to 8 Days | No longer meets study criteria | 0 | 1 | 0 |
| Open Label Period-Up to 96 Weeks | Adverse Event | 3 | 2 | 4 |
| Open Label Period-Up to 96 Weeks | Death | 1 | 7 | 15 |
| Open Label Period-Up to 96 Weeks | Lack of Efficacy | 3 | 9 | 6 |
| Open Label Period-Up to 96 Weeks | Lost to Follow-up | 4 | 3 | 1 |
| Open Label Period-Up to 96 Weeks | No longer meets criteria | 0 | 4 | 4 |
| Open Label Period-Up to 96 Weeks | Non-compliance with study drug | 3 | 8 | 6 |
| Open Label Period-Up to 96 Weeks | Ongoing at the time of analysis | 54 | 159 | 61 |
| Open Label Period-Up to 96 Weeks | Other | 0 | 1 | 1 |
| Open Label Period-Up to 96 Weeks | Pregnancy | 0 | 1 | 0 |
| Open Label Period-Up to 96 Weeks | Withdrawal by Subject | 0 | 5 | 1 |
Baseline characteristics
| Characteristic | Randomized Cohort-Placebo | Randomized Cohort-fostemsavir 600 mg BID | Non-randomized Cohort-fostemsavir 600 mg BID-Open Label Period | Total |
|---|---|---|---|---|
| Age, Continuous | 43.0 Years STANDARD_DEVIATION 11.02 | 45.2 Years STANDARD_DEVIATION 12.72 | 48.1 Years STANDARD_DEVIATION 11.53 | 45.6 Years STANDARD_DEVIATION 12.2 |
| Race/Ethnicity, Customized Race customized American Indian or Alaska Native | 1 Participants | 6 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Race customized Asian | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race customized Black or African American | 18 Participants | 42 Participants | 23 Participants | 83 Participants |
| Race/Ethnicity, Customized Race customized Brown | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race customized Hispanic | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race customized Mestizo | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race customized Mixed | 1 Participants | 6 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Race customized Mulatto | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race customized Native Hawaiian or other Pacific islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race customized North African | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race customized White | 48 Participants | 137 Participants | 74 Participants | 259 Participants |
| Race/Ethnicity, Customized Race customized White and African descent | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 12 Participants | 60 Participants | 10 Participants | 82 Participants |
| Sex: Female, Male Male | 57 Participants | 143 Participants | 89 Participants | 289 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 69 | 10 / 203 | 17 / 99 | 12 / 271 | 29 / 370 |
| other Total, other adverse events | 16 / 69 | 45 / 203 | 92 / 99 | 214 / 271 | 306 / 370 |
| serious Total, serious adverse events | 2 / 69 | 4 / 203 | 48 / 99 | 92 / 271 | 140 / 370 |
Outcome results
Primary
Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort
Plasma samples were collected for analysis of HIV-1 RNA. Mean change in log10 HIV-1 RNA from Day 1 was estimated using analysis of covariance (ANCOVA) with log10 HIV-1 RNA change from Day 1 at Day 8 as dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 log10 HIV-1 RNA as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. The 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 treatment. Missing HIV-1 RNA values at Day 8 were imputed using (a) Day 1 Observation Carried Forward (D1OCF) for participants without a value during blinded treatment (i.e, imputing a zero change from Day 1) or (b) Last Observation Carried Forward (LOCF) for participants with an early value during blinded treatment before the Day 8 analysis visit window.
Time frame: Day 1 and Day 8
Population: ITT-E Population. Participants with missing Day 1 HIV-1 RNA values were not analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Randomized Cohort-Placebo | Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort | -0.166 Log10 copies per milliliter (c/mL) |
| Randomized Cohort-fostemsavir 600 mg BID | Mean Change in Logarithm to the Base 10 (log10) HIV-1 Ribonucleic Acid (RNA) From Day 1 at Day 8-Randomized Cohort | -0.791 Log10 copies per milliliter (c/mL) |
p-value: <0.000195% CI: [-0.81, -0.441]ANCOVA
Secondary
Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96
Percentage CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline.
Time frame: Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
Population: ITT-E Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 12; n=249 | 3.00 Percentage of CD4+ T- cells | Standard Deviation 4.945 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Day 8; n=255 | 0.75 Percentage of CD4+ T- cells | Standard Deviation 1.97 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 4; n=259 | 2.30 Percentage of CD4+ T- cells | Standard Deviation 4.643 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 8; n=254 | 2.36 Percentage of CD4+ T- cells | Standard Deviation 4.392 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 16; n=245 | 3.51 Percentage of CD4+ T- cells | Standard Deviation 4.979 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 24; n=247 | 4.26 Percentage of CD4+ T- cells | Standard Deviation 4.828 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 36; n=234 | 5.06 Percentage of CD4+ T- cells | Standard Deviation 5.256 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 48; n=228 | 6.51 Percentage of CD4+ T- cells | Standard Deviation 5.531 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 60; n=215 | 7.00 Percentage of CD4+ T- cells | Standard Deviation 5.94 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 72; n=217 | 7.02 Percentage of CD4+ T- cells | Standard Deviation 5.726 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 84; n=203 | 7.68 Percentage of CD4+ T- cells | Standard Deviation 5.798 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Percentage Through Week 96 | Week 96; n=213 | 8.44 Percentage of CD4+ T- cells | Standard Deviation 6.409 |
Secondary
Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort
CD4+ T- cell counts were assessed by flow cytometry. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline.
Time frame: Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
Population: ITT-E Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Day 8; n=255 | 19.8 Cells per cubic millimeter | Standard Deviation 60.98 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 4; n=259 | 48.9 Cells per cubic millimeter | Standard Deviation 131.75 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 8; n=254 | 61.5 Cells per cubic millimeter | Standard Deviation 113.47 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 12; n=249 | 79.0 Cells per cubic millimeter | Standard Deviation 123.31 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 16; n=245 | 84.1 Cells per cubic millimeter | Standard Deviation 107.26 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 24; n=247 | 90.4 Cells per cubic millimeter | Standard Deviation 112.1 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 36; n=234 | 109.7 Cells per cubic millimeter | Standard Deviation 119.5 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 48; n=228 | 138.9 Cells per cubic millimeter | Standard Deviation 135.06 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 60; n=215 | 162.9 Cells per cubic millimeter | Standard Deviation 157.69 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 72; n=217 | 172.1 Cells per cubic millimeter | Standard Deviation 184.81 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 84; n=203 | 190.8 Cells per cubic millimeter | Standard Deviation 165.63 |
| Randomized Cohort-Placebo | Change From Baseline in CD4+ T- Cell Count Through Week 96-Randomized Cohort | Week 96; n=213 | 204.7 Cells per cubic millimeter | Standard Deviation 191.28 |
Secondary
Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort
Blood samples were collected for the analysis of HIV-1 RNA. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as the value at post-dose visit minus the value at Baseline. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time frame: Baseline and at Day 8, Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84 and 96
Population: ITT-E Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 8; n=256 | -2.207 Log10 c/mL | Standard Deviation 1.1416 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Day 8; n=262 | -0.656 Log10 c/mL | Standard Deviation 0.7536 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 4; n=262 | -2.051 Log10 c/mL | Standard Deviation 1.0717 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 12; n=248 | -2.237 Log10 c/mL | Standard Deviation 1.2105 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 16; n=249 | -2.277 Log10 c/mL | Standard Deviation 1.2834 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 24; n=246 | -2.297 Log10 c/mL | Standard Deviation 1.2788 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 36; n=238 | -2.332 Log10 c/mL | Standard Deviation 1.2265 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 48; n=233 | -2.324 Log10 c/mL | Standard Deviation 1.2876 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 60; n=223 | -2.419 Log10 c/mL | Standard Deviation 1.1973 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 72; n=221 | -2.427 Log10 c/mL | Standard Deviation 1.1542 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 84; n=215 | -2.455 Log10 c/mL | Standard Deviation 1.193 |
| Randomized Cohort-Placebo | Change From Baseline in log10 HIV-1 RNA for Fostemsavir When Given With OBT Through Week 96-Randomized Cohort | Week 96; n=214 | -2.476 Log10 c/mL | Standard Deviation 1.1984 |
Secondary
Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort
CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell counts from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an in-dependent variable, and Day 1 CD4+ cell count as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (i.e., imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window.
Time frame: Day 1 and Day 8
Population: ITT-E Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Randomized Cohort-Placebo | Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort | 18.9 Cells per cubic millimeter |
| Randomized Cohort-fostemsavir 600 mg BID | Change From Day 1 in Cluster of Differentiation (CD) 4+ T-cell Count at Day 8-Randomized Cohort | 18.5 Cells per cubic millimeter |
95% CI: [-16.8, 16]
Secondary
Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort
CD4+ T- cell counts were assessed by flow cytometry. Mean change in CD4+ T- cell count percentage from Day 1 at Day 8 was analyzed using one-way ANCOVA with change of CD4+ cell count percentage from Day 1 at Day 8 as the dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 CD4+ cell count percentage as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. Missing CD4+ cell count values at Day 8 were imputed using (a) D1OCF for participants without a value during blinded treatment (ie, imputing a zero change from Day 1), or (b) LOCF for participants with an early value during blinded treatment before the Day 8 analysis visit window.
Time frame: Day 1 and Day 8
Population: ITT-E Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Randomized Cohort-Placebo | Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort | 0.243 Percentage of CD4+T- cells |
| Randomized Cohort-fostemsavir 600 mg BID | Change in CD4+ T- Cell Count Percentage From Day 1 at Day 8-Randomized Cohort | 0.860 Percentage of CD4+T- cells |
95% CI: [0.082, 1.151]
Secondary
Number of Participants With Centers for Disease Control (CDC) Class C Events-Randomized Cohort
Disease progression during open label fostemsavir plus OBT was assessed based on the occurrence of new AIDS defining events (CDC Class C events) or death. The number of participants with on-treatment CDC Class C AIDS events is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time frame: Up to Week 96 analysis cut-off date
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Cohort-Placebo | Number of Participants With Centers for Disease Control (CDC) Class C Events-Randomized Cohort | 23 Participants |
Secondary
Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort
The phenotypic resistance to a drug is defined in terms of a fold change (FC) in IC50s, i.e., the ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of a reference strain (wild type control). FCR was calculated as FC at PDVF divided by Baseline FC. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. FCR\<1 indicates that FC is smaller on-treatment than at Baseline. FCR \>3 indicates that on-treatment FC is 3 times greater than it was at Baseline.
Time frame: Week 96
Population: PDVF through Week 96 Population. Only participants available at the specified time point were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Cohort-Placebo | Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | <=1 | 19 Participants |
| Randomized Cohort-Placebo | Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | >1 to 3 | 10 Participants |
| Randomized Cohort-Placebo | Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | >3 to 10 | 5 Participants |
| Randomized Cohort-Placebo | Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | >10 to 100 | 1 Participants |
| Randomized Cohort-Placebo | Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | >100 to 3000 | 10 Participants |
| Randomized Cohort-Placebo | Number of Participants With Indicated Fold Change Ratio (FCR) Using the Monogram PhenoSense Entry Assay-Randomized Cohort | >3000 | 8 Participants |
Secondary
Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort
An SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or causes prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; an important medical event that may jeopardize the participant or require intervention. Number of participants with on-treatment SAEs and AEs leading to withdrawal of study treatment is presented. SAEs and AELDs were collected in Safety Population which comprised of all participants who received at least one dose of study treatment. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time frame: Up to Week 96 analysis cut-off date
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Cohort-Placebo | Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort | SAE | 92 Participants |
| Randomized Cohort-Placebo | Number of Participants With On-treatment Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Discontinuation (AELD)-Randomized Cohort | AELD | 14 Participants |
Secondary
Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort
Laboratory toxicities were graded for severity according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with clinical chemistry toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time frame: Baseline and up to Week 96 analysis cut-off date
Population: Safety Population. Only participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Creatinine; n=268 | 52 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Albumin; n=268 | 1 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Alkaline phosphatase; n=268 | 3 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Alanine aminotransferase; n=268 | 14 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Amylase; n=268 | 2 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Aspartate aminotransferase; n=268 | 10 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Bicarbonate; n=268 | 1 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Direct bilirubin; n=268 | 20 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Bilirubin; n=268 | 7 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Calcium; n=268 | 9 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Cholesterol; n=221 | 10 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Creatine kinase; n=268 | 6 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Estimated creatinine clearance; n=268 | 75 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Glucose/hyperglycemia; n=267 | 6 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Glucose/hypoglycemia; n=267 | 2 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Potassium/hyperkalemia; n=268 | 4 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Potassium/hypokalemia; n=268 | 0 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Low density lipoprotein (LDL) cholesterol; n=216 | 8 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Lipase; n=268 | 13 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Sodium/hypernatremia; n=268 | 0 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Sodium/hyponatremia; n=268 | 0 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Triglycerides; n=221 | 11 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Clinical Chemistry Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Urate; n=268 | 9 Participants |
Secondary
Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort
Laboratory toxicities were graded for severity according to the DAIDS grading system: Grade 1 (mild); Grade 2 (moderate); Grade 3 (severe); Grade 4 (potentially life-threatening). Baseline is defined as the latest pre-dose assessment. The number of participants with hematology toxicity grade increase to Grade 3-4 at anytime post-Baseline relative to Baseline is presented. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time frame: Baseline and up to Week 96 analysis cut-off date
Population: Safety Population. Only participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Hemoglobin; n=268 | 16 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Neutrophils; n=268 | 10 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Platelets; n=267 | 2 Participants |
| Randomized Cohort-Placebo | Number of Participants With Toxicity Grade Increase in Hematology Results to Grade 3-4 Relative to Baseline-Randomized Cohort | Leukocytes; n=268 | 4 Participants |
Secondary
Number of Participants With Treatment-emergent Viral Genotypic Substitution of Interest in the GP160 Domain as a Measure of Genotypic Resistance-Randomized Cohort
Plasma samples were collected for emergent drug resistance testing. The number of participants with emergent viral genotypic substitutions of interest in the GP160 domain was identified by the next-generation sequencing (NGS) assay. Protocol defined virologic failure (PDVF) through Week 96 Population comprised of all participants with available phenotypic and genotypic resistance data meeting at the time protocol defined virologic failure (PDVF) was met. The criteria for PDVF was a) Confirmed, or last available prior to discontinuation, HIV-1 RNA \>=400 c/mL at any time after prior confirmed suppression to \<400 c/mL prior to Week 24 or Confirmed, or last available prior to discontinuation, \> 1 log10 c/mL increase in HIV-1 RNA at any time above nadir level where nadir is \>=40 c/mL prior to Week 24. b) Confirmed, or last available prior to discontinuation, HIV-1 RNA \>=400 c/mL at or after Week 24.
Time frame: Week 96
Population: PDVF through Week 96 Population. Only participants available at the specified time point were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Randomized Cohort-Placebo | Number of Participants With Treatment-emergent Viral Genotypic Substitution of Interest in the GP160 Domain as a Measure of Genotypic Resistance-Randomized Cohort | 24 Participants |
Secondary
Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort
The durability of response (that is, the number of participants achieving HIV-1 RNA \<40 c/mL) at Weeks 24, 48 and 96 of open-label fostemsavir plus OBT in the Randomized Cohort was assessed using the Food and Drug Administration (FDA) snapshot algorithm in which participants without HIV-1 RNA at Weeks 24, 48 and 96 or those who changed OBT due to lack of efficacy through Weeks 24, 48 and 96 were counted as failures. The percentage of participants in the Randomized Cohort who achieved virologic success (HIV-1 RNA \<40 c/mL) at Weeks 24, 48 and 96 is presented along with 95% Wilson confidence interval. All the participants received fostemsavir during the open-label period irrespective of the original arms to which they were randomized; hence, the combined totals for Randomized Cohort is presented as pre-specified in protocol and reporting and analysis plan.
Time frame: At Weeks 24, 48 and 96
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Cohort-Placebo | Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort | Week 24 | 53 Percentage of participants |
| Randomized Cohort-Placebo | Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort | Week 48 | 54 Percentage of participants |
| Randomized Cohort-Placebo | Percentage of Participants With HIV-1 RNA <40 c/mL at Weeks 24, 48 and 96-Randomized Cohort | Week 96 | 60 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort
The percentage of participants in the Randomized Cohort with HIV-1 RNA decreases from Day 1 that exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8 was determined by comparing HIV-1 RNA Day 1 measurement of each participant to their Day 8 measurement. This was an ITT analysis that classified participants without HIV-1 RNA at Day 1 or Day 8 as failures. The percentage of responders along with 95% confidence interval based on Wilson score is presented.
Time frame: Day 1 and Day 8
Population: ITT-E Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Randomized Cohort-Placebo | Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort | >0.5 log10 c/mL | 18.84 Percentage of participants |
| Randomized Cohort-Placebo | Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort | >1.0 log10 c/mL | 10.14 Percentage of participants |
| Randomized Cohort-fostemsavir 600 mg BID | Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort | >0.5 log10 c/mL | 64.53 Percentage of participants |
| Randomized Cohort-fostemsavir 600 mg BID | Percentage of Participants With HIV-1 RNA Decreases From Day 1 That Exceed 0.5 log10 c/mL and 1.0 log10 c/mL at Day 8-Randomized Cohort | >1.0 log10 c/mL | 45.81 Percentage of participants |
95% CI: [32.95, 55.45]
95% CI: [24.16, 44.25]