CROI 2016 Abstract eBook
471 Tolerability and Acceptability of Cabotegravir LA Injection: Results From ECLAIR Study
Miranda I. Murray 1 ; Martin Markowitz 2 ; Ian Frank 3 ; Robert Grant 4 ; Kenneth H. Mayer 5 ; David A. Margolis 6 ; Krischan J. Hudson 7 ; Britt S. Stancil; Alex R. Rinehart;William Spreen 6 1 ViiV Hlthcare, Brentford, UK; 2 Aaron Diamond AIDS Rsr Cntr, New York, NY, USA; 3 Perelman Sch of Med, Univ of Pennsylvania, Philadelohia, PA, USA; 4 Univ of California San Francisco, San Francisco, CA, USA; 5 The Fenway Inst, Fenway Hlth, Boston, MA, USA; 6 ViiV Hlthcare, Research Triangle Park, NC, USA; 7 ViiV Hlthcare, Reserach triangle Park, NC, USA Background: Cabotegravir (CAB, GSK 1265744) is a Long-Acting (LA) injectable, in Phase 2 for treatment and prevention of HIV-1 infection. ÉCLAIR evaluated CAB LA injections for HIV PrEP. Secondary objectives include tolerability, satisfaction, and acceptability of CAB LA. Methods: ÉCLAIR is a double-blind, randomised, multi-centre study in HIV-negative men, excluding males at high-risk of HIV-1. Participants were randomized (5:1) to QD oral CAB 30mg or placebo (PBO) for 4 weeks (W); thereafter IM injections (Inj) of 800mg CAB LA or PBO (saline) q12W x 3 cycles. Satisfaction, tolerability, and acceptability were self- assessed with Study Medication Satisfaction Questionnaire (SMSQ) with 11 items adapted from the HIV-Treatment Satisfaction Questionnaire and Study Medication Questionnaire (SMQ), which consists of 4 items evaluating adherence with study medication. SMSQ and SMQ were administered at W 6, 18, and 30 (1W after CAB LA inj). Results: ECLAIR randomized/treated 126 participants (CAB: 105; PBO 21). Eighteen withdrew from CAB: five during oral phase, six after oral but prior to inj, and seven during the inj phase. Of those receiving inj, 87/94 (93%) of CAB LA, and 20/21 (95%) PBO completed inj phase. AEs due to CAB included inj site pain (82%), headache (23%), and inj site swelling (20%). 1W following second inj, the majority of participants were more satisfied with IM CAB compared with once daily oral CAB, on all 11 items included in the SMSQ [figure below]. At 1W post third CAB LA inj, 64/86 (75%) of participants were satisfied with CAB IM, 21% neither satisfied nor dissatisfied and, 4% dissatisfied. Overall, 75/86 (87%) of participants reported as willing to recommend medication and 68/86 (79%) a willingness to continue with study medication. Tolerability of CAB LA inj showed 57/86 (66%) of participants were satisfied with side effects with 13% neither satisfied or dissatisfied and 55/86 (64%) were satisfied with the amount of pain/discomfort with 14% neither satisfied or dissatisfied. SMQ results show 73/86 (85%) of participants almost never found it difficult to comply with the q12W schedule. Conclusions: Secondary endpoints from ECLAIR help interpretation of safety data and provide a robust participant-centred perspective. While CAB LA inj site pain was common, discontinuation was infrequent. Results suggest participants experienced a high level of overall satisfaction and cited preference for a LA inj based on dimensions such as convenience, flexibility and ease of use.
472 Attachment Inhibitor Prodrug BMS-663068 in ARV-Experienced Subjects: Week 96 Analysis
Edwin DeJesus 1 ; Marcelo Martins 2 ; Albrecht Stoehr 3 ; Jaime Andrade-Villanueva 4 ; Natalia Zakharova 5 ; David A Stock 6 ; Cyril Llamoso 6 ; Samit R. Joshi 6 ; George J. Hanna 7 ; Max Lataillade 6 1 Orlando Immunology Cntr, Orlando, FL, USA; 2 Inst Oulton, Córdoba, Argentina; 3 IFI Inst for Interdisciplinary Med, Hamburg, Germany; 4 Hosp Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico; 5 St Petersburg AIDS Cntr, St Petersburg, Russian Federation; 6 Bristol-Myers Squibb, Wallingford, CT, USA; 7 Bristol-Myers Squibb, Princeton, NJ, USA Background: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial viral attachment and entry into host CD4+ T-cells. AI438011 is an ongoing Phase 2b, randomized, controlled trial investigating the safety, efficacy and dose–response of four doses of BMS-663068 vs atazanavir/ritonavir (ATV/r) in treatment-experienced (TE) HIV-1-infected subjects. At Week 24/48 BMS‑663068 had similar response rates across all doses and to ATV/r and was generally well tolerated. We report results through Week 96. Methods: TE adults (≥1 week exposure to ≥1 ARV) with viral loads (VL) ≥1,000 c/mL and susceptibility to BMS-663068 (BMS-626529 IC 50 <100 nM), raltegravir (RAL), tenofovir disoproxil fumarate (TDF), and ATV were randomized equally to four BMS-663068 arms (400 or 800 mg BID; 600 or 1200 mg QD) and a control (ATV/r 300/100 mg QD), each with a backbone of RAL 400 mg BID+TDF 300 mg QD. BMS-663068 1200 mg QD was selected as the open-label continuation dose after Week 48 and pooled efficacy and safety results for BMS-663068 are included. Results: 254 subjects were randomized and 251 treated across all arms. Median age was 39 years, 60%were male, 62%were non-white. Median baseline (BL) VL was 4.85 log 10 c/mL (43%≥100,000 c/mL); median CD4+ T-cell count was 230 cells/µL (38%<200 cells/µL). In total, 67% (167/251) subjects completed 96 weeks of therapy. At Week 96, 61% of BMS-663068- and 53% of ATV/r-treated subjects had HIV-1 RNA <50 c/mL (mITT; Table). In the observed analysis, 90% of BMS-663068- and 90% of ATV/r-treated subjects had HIV-1 RNA <50 c/mL (Table). Observed virologic response rates for BMS-663068 vs ATV/r by BL VL <100,000 c/mL were 87% vs 95%, respectively, and by BL VL ≥100,000 c/mL were 94% vs 80%, respectively. Mean increase in CD4+ T-cell count from BL through Week 96 was 219 cells/µL for BMS-663068 and 250 cells/µL for ATV/r. BMS-663068 was generally well tolerated and no BMS-663068-related AEs led to discontinuation (D/C). Conclusions: At Week 96, BMS-663068 continued to show similar virologic response rates (mITT and observed) and immunologic reconstitution to ATV/r in TE subjects. BMS- 663068 was generally well tolerated and no BMS-663068-related AEs led to D/C. These results support the ongoing Phase III trial evaluating BMS-663068 in heavily TE adults with limited therapeutic options (≤2 classes of active antiretrovirals remaining) due to resistance, tolerability issues and contraindications (NCT02362503).
Made with FlippingBook - Online catalogs