WASHINGTON STATE CONVENTION CENTER

February 13–16, 2017

Conference Dates and Location: 
February 23-26, 2015 | Seattle, Washington
Abstract Number: 
554LB

Cabotegravir and Rilpivirine As 2-Drug Oral Maintenance Therapy: LATTE W96 Results

Author(s): 

David A. Margolis1, Cynthia C. Brinson2, Graham H. Smith3, Jerome de Vente4, Debbie P. Hagins5, Sandy K. Griffith1, Marty H. St. Clair1, Kimberly Y. Smith6, Peter E. Williams7, William R. Spreen1
1 GlaxoSmithKline, Durham, NC, United States. 2 Central Texas Clinical Research, Austin, TX, United States. 3 Maple Leaf Medical Clinic, Toronto, ON, Canada. 4 Living Hope Foundation, Long Beach, CA, United States. 5 Chatham County Health Department, Savannah, GA, United States. 6 ViiV Healthcare, Durham, NC, United States. 7 Janssen Pharmaceuticals, Inc, Beerse, Belgium.

Abstract Body: 

Background: Cabotegravir (CAB, GSK744) is an HIV INSTI under development as both an oral and long-acting (LA) injectable. LATTE was designed to select an oral dose of CAB and to evaluate a two-drug ART regimen with rilpivirine (RPV), as suppressive maintenance therapy.

Methods: Phase 2b, multicentre, partially-blinded, dose-ranging study in ART-naïve HIV infected adults, randomized 1:1:1:1 to the induction regimen of once daily oral CAB 10 mg, 30 mg, 60 mg or efavirenz (EFV) 600 mg with TDF/FTC or ABC/3TC through Week (W) 24, followed by a two-drug oral maintenance regimen of CAB (blinded dose) + RPV 25 mg through W96. CAB patients (pts) with a VL <50 c/mL immediately prior to W24 discontinued NRTIs and began RPV 25 mg; no change was made for EFV + NRTIs pts (ITT-Maintenance Exposed (ME)).

Results: 243 pts were randomized and treated (ITT-E): 96% male, 38% non-white, 14%>100,000 c/mL HIV-1 RNA, 61% TDF/FTC. Amongst pts who began CAB + RPV at W24, 86% had HIV-1 RNA <50 c/mL by snapshot at W96 overall, relative to 83% of pts continuing EFV (ITT-ME). Five protocol-defined virologic failures occurred during 72 weeks of Maintenance (CAB 10 mg [2], CAB 30 mg [1], EFV [2] including two on CAB + RPV with treatment emergent resistance [INI + NNRTI, NNRTI]). Drug-related AEs ≥ Grade 2 were reported by 14% and 19% of CAB and EFV pts, respectively with 4% and 4% occurring during the 72W Maintenance phase. SAEs occurred in 10% of CAB pts (none drug related); and 6% EFV pts (one drug-related - suicide attempt). Fewer CAB pts withdrew due to AEs (3%), than EFV pts (15%), mostly prior to the Maintenance phase. Treatment-emergent lab abnormalities ≥ Grade 3 occurred in 26% of CAB and 37% of EFV pts through W96, most commonly elevated creatine kinase. Rates of any graded ALT elevations were 20% with CAB and 21% with EFV.

Conclusions: When used as two-drug maintenance therapy in virologically suppressed pts, CAB + RPV provided similar antiviral activity to EFV+2 NRTIs through W96. CAB + RPV was well tolerated overall, with no SAEs considered drug related and few AEs leading to withdrawal. Considering all safety and efficacy data, oral CAB 30mg once-daily was selected for further development. Results support the selected dose regimens for the ongoing Ph2 LATTE-2 study with CAB LA + RPV LA as injectable two-drug maintenance therapy.

Snapshot Study Outcomes CAB
10 mg
(n=60)
CAB
30 mg
(n=60)
CAB
60 mg
(n=61)
CAB
Subtotal
(n=181)
EFV
Control
(n=62)
%<50c/mL at W96 Snapshot (ITT-E) (95%CI)++ 41 (68%)
(57%,80%)
45 (75%)
(64%,86%)
51 (84%)
(74%,93%)
137 (76%)
(69%,82%)
39 (63%)
(51%,75%)
Protocol-defined Virologic Failure 3 (5%) 2 (3%) 1 (2%) 6 (3%) 6 (10%)
Failure due to Adverse Event 1 (2%) 1 (2%) 4 (7%) 6 (3%) 9 (15%)
Failure due to HIV-1 RNA ≥50 c/mLÂ¥ 5 (8%) 1 (2%) 2 (3%) 8 (4%) 2 (3%)
Failure due to Other Reasons While Not Suppressed+ 2 (3%) 2 (3%) 1 (2%) 5 (3%) 3 (5%)
Failure due to Other Reasons While Suppressed+ 8 (13%) 9 (15%) 2 (3%) 19 (10%) 3 (5%)
Other Results
<50 c/mL at W96 Snapshot (ITT-ME) 41/52
(79%)
45/53
(85%)
51/55
(93%)
137/160
(86%)
39/47*
(83%)
Grade 2-4 Drug Related AEs 5 (8%) 8 (13%) 13 (21%) 26 (14%) 12 (19%)
Median Baseline CD4+ cells/mm3 (Change from Baseline at W96) 415.0
(236.5)
404.0
(249.5)
420.0
(271.5)
412.0
(259.5)
416.5
(289.0)
Â¥ HIV-1 RNA ≥50 c/mL reasons include HIV-1 RNA ≥50c/mL at Week 96 or discontinued while not suppressed (≥50 c/mL) for Lack of Efficacy
+ Other reasons include missing data; protocol deviation, non-compliance, lost to follow-up, withdrawn consent, investigator discretion, ART change, and ineligible for Maintenance phase
++W96 represents a 24 Week Induction phase followed by a 72 Week Maintenance phase
*EFV pts with a W24 visit (n=47)
Intent to Treat-Exposed (ITT-E) and Intent to Treat- Maintenance Exposed (ITT-ME)

 

Session Number: 
P-J1
Session Title: 
ART: Recent Perspectives
Presenting Author: 
Margolis, David
Presenter Institution: 
GlaxoSmithKline
Poster: