containing the following 3:
containing the following as fully active agents 4:
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For heavily treatment-experienced adults with HIV-1 failing therapy. See Full Indication.
BRIGHTE was a Phase 3, international, double-blind, placebo-controlled trial that evaluated the efficacy and safety of RUKOBIA in people living with multidrug-resistant HIV-1.2 The significant antiviral activity of RUKOBIA at Day 8, as well as long-term data through Week 240, is presented below. Additional endpoints in BRIGHTE for RUKOBIA include virologic suppression and change in CD4+ T-cell counts.
All participants in BRIGHTE were failing on their current ARV regimens with viral loads of ≥400 copies/mL at enrollment
BRIGHTE Trial Design
Secondary Endpoints1:
*Two participants in the RUKOBIA + failing regimen arm who had missing Day 1 HIV-1 RNA values were not included in the analysis at Day 8.
†Within the nonrandomized cohort (n=99), 15 participants received ibalizumab, an investigational agent at the start of the RUKOBIA Phase 3 trial, and 4 received an approved antiretroviral drug and were classified as having a protocol violation.
Participants in the randomized cohort (n=272) had 1 to 2 classes of ARVs remaining at baseline1,3
Additional Baseline Information1
ARV=antiretroviral; HIV-1=human immunodeficiency virus type-1; MDR=multidrug-resistant; OBT=optimized background therapy.
BASELINE CHARACTERISTICS IN THE RANDOMIZED COHORT1,3
Parameter | Total participants (n=272) |
Age, years | |
Median (min, max) | 48 (18-73) |
Age, n (%) | |
<50 years | 162 (60) |
≥50 years | 110 (40) |
Gender, n (%) | |
Male | 200 (74) |
Female | 72 (26) |
Race, n (%) | |
White | 185 (68) |
Black/African American | 60 (22) |
Other Races | 27 (10)* |
HIV-1 RNA (log10 copies/mL) | |
Median (min, max) | 4.7 (1.6-6.9) |
HIV-1 RNA copies/mL, n (%) | |
<400 | 21 (8)† |
400 to <1000 | 10 (4) |
1000 to <100,000 | 161 (59) |
≥100,000 | 80 (29) |
CD4+ T-cells/mm3 | |
Median (min, max) | 99 (0-1160) |
CD4+ T-cells/mm3, n (%) | |
<20 | 72 (26) |
20 to <50 | 25 (9) |
50 to <200 | 102 (38) |
200 to <500 | 58 (21) |
≥500 | 15 (6) |
Number of Fully Active and Available ARVs in Initial OBT, n (%) | |
0 | 16 (6)‡ |
1 | 142 (52) |
2 | 114 (42) |
History of AIDS Diagnosis, n (%) | |
Prior or current history | 231 (85) |
*Other includes American Indian/Alaskan Native (n=7), Native Hawaiian/Other Pacific Islander (n=1), Asian (n=2) and other (n=17)3,4. Ethnicity was also recorded for 262 participants (including all US participants and some non-US participants), 107 (29%) of whom identified as Hispanic or Latino.
*All the participants had an HIV-1 RNA level of >400 copies per mL at the time of enrollment.1
‡lncludes participants who never initiated OBT, were incorrectly assigned to the randomized cohort, or had 1 or more active antiretroviral agents available at screening but did not use these as part of the initial OBT.3
Among participants in the nonrandomized cohort:
BASELINE CHARACTERISTICS IN THE NONRANDOMIZED COHORT (N=99)3,4,5
Parameter | RUKOBIA 600-mg BID + OBT |
Age, years | |
Median (min, max) | 50 (17, 72) |
Age, n (%) | |
<50 years | 44 (44) |
≥50 years | 55 (56) |
Gender, n (%) | |
Male | 89 (90) |
Female | 10 (10) |
Race, n (%) | |
White | 74 (75) |
Black/African American | 23 (23) |
Other Races | 2 (2)* |
HIV-1 RNA (log10 copies/mL) | |
Median (min, max) | 4.3 (1.59, 6.61) |
HIV-1 RNA log10 copies/mL, n (%) | |
<400 | 5 (5) |
400 to <1000 | 4 (4) |
1000 to <100,000 | 75 (76) |
≥100,000 | 15 (15) |
CD4+ T-cells/mm3 | |
Median (min, max) | 41 (0, 641) |
CD4+ T-cells/mm3, n (%) | |
<20 | 40 (40) |
20 to <50 | 14 (14) |
50 to <200 | 25 (25) |
200 to <500 | 18 (18) |
≥500 | 2 (2) |
Number of Fully Active and Available ARVs in Initial OBT, n (%) | |
0 | 80 (81) |
1 | 19 (19)† |
History of AIDS Diagnosis, n (%) | |
Prior or current history | 89 (90) |
*Other includes American Indian/Alaskan Native (n=1), Native Hawaiian/Other Pacific Islander (n=0), Asian (n=0), and other (n=1).3,4
†Of the 19 participants, 15 received ibalizumab, which was an investigational agent at the start of BRIGHTE. Four patients had 1 fully active ARV class remaining and were classified as a protocol deviations.5
BRIGHTE evaluated the efficacy of RUKOBIA among randomized patients (n=272) through Week 240. The primary endpoint was based on the adjusted mean plasma HIV-1 RNA log10 change from Day 1 at Day 82
PRIMARY ENDPOINT (RANDOMIZED COHORT): DECLINE IN MEAN PLASMA VIRAL LOAD
*Two participants who received RUKOBIA with missing Day 1 HIV-1 RNA values were not included in this analysis.
CI=confidence interval.
VIROLOGIC RESPONSE WITH RUKOBIA + OBT IN THE RANDOMIZED COHORT: ITT-E POPULATION IN SNAPSHOT ANALYSIS (N=272) AND PARTICIPANTS IN OBSERVED ANALYSIS2
Included in the Snapshot Analysis5
Included in the Observed Analysis5
*At Week 240, 5 participants had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval was in the US in July 2020).2
FDA=Food and Drug Administration
ITT-E=intent-to-treat-exposed; OBT=optimized background therapy; PLWH=people living with HIV-1
SECONDARY ENDPOINT (NONRANDOMIZED COHORT) VIROLOGIC RESPONSE WITH RUKOBIA + OBT2
*At Week 240, 7 participants had completed the study by transitioning to locally approved fostemsavir (the first fostemsavir approval in the US was in July 2020).2
SECONDARY ENDPOINT (RANDOMIZED COHORT): VIROLOGIC RESPONSE WITH RUKOBIA + OBT Through ~5 YEARS* BY SUBGROUPS4
Subgroup | % of Participants Virologically Suppressed (HIV-1 RNA <40 copies/mL) |
Age, years | |
<35 | 39% (24/61) |
35 to <50 | 48% (48/100) |
>50 | 45% (48/106) |
Race | |
White | 43% (78/183) |
Black or African American | 48% (28/58) |
American Indian or Alaska Native | 43% (3/7) |
Native Hawaiian or other Pacific Islander | 0% (0/1) |
Asian | 50% (1/2) |
Other Races | 63% (10/16) |
Gender | |
Male | 45% (90/198) |
Female | 43% (30/69) |
*Based on BRIGHTE 240-week data.
PROTOCOL-DEFINED VF WITH RUKOBIA + OBT2
PDVF was defined as the following: before Week 24, confirmed HIV-1 RNA ≥400 copies/mL after confirmed suppression to <400 copies/mL or confirmed >1 log10 copies/mL increase in HIV-1 RNA above nadir where nadir is ≥40 copies/mL; at or after Week 24, confirmed HIV-1 RNA ≥400 copies/mL.
*Through Week 96, the PI for RUKOBIA identifies 69 of 272 (25%) participants in the randomized cohort and 50 of 99 (51%) of participants in the non-randomized cohort as experiencing VF. The definition for VF used in the PI differs from the definition of PDVF. Per the PI, VF=confirmed ≥400 copies/mL after prior confirmed suppression to <400 copies/mL, ≥400 copies/mL at last available prior to discontinuation, or >1 log10 copies/mL increase in HIV-1 RNA at any time above nadir level (≥40 copies/mL).
BID=twice daily; gp120=glycoprotein 120; HIV-1=human immunodeficiency virus type-1; ITT-E=intent-to-treat–exposed; OBT=optimized background therapy; PI=prescribing information; PDVF=protocol-defined virologic failure; VF=virologic failure.
SECONDARY ENDPOINT (NONRANDOMIZED COHORT): INCREASE IN CD4+ T-CELLS FROM BASELINE WITH RUKOBIA + OBT THROUGH ~5 YEARS2
*At Week 240,19 participants did not have their data included in this analysis due to the impact of COVID-19.
References:
FSTWCNT230013