WEEK 8 RESULTS OF AMBER: A PHASE 3, RANDOMISED, DOUBLE-BLIND TRIAL IN ANTIRETROVIRAL TREATMENT (ART)-NAÏVE HIV--INFECTED ADULTS TO EVALUATE THE EFFICACY AND SAFETY OF THE ONCE-DAILY, SINGLE-TABLET REGIMEN (STR) OF DARUNAVIR/ COBICISTAT/ EMTRICITABINE/ TENOFOVIR ALAFENAMIDE () VERSUS DARUNAVIR/COBICISTAT (DRV/C) PLUS EMTRICITABINE/ TENOFOVIR DISOPROXIL FUMARATE (FTC/TDF) J. Gallant, C. Orkin, J.-M. Molina, E. Negredo, A. Antinori, A. Mills, J. Eron, J. Reynes, E. Van Landuyt, E. Lathouwers, V. Hufkens, J. Jezorwski, M. Opsomer Abstract PS8/ DESIGN Double-blind treatment phase Roll-over phase Treatment-naïve adults Screening plasma VL, c/ml CD+ >5 cells/mm3 Genotypic susceptibility to DRV, FTC and TFV HBV/HCV negative Single-arm phase Randomised + matching D/C + F/TDF placebo : N=75 D/C + F/TDF + matching placebo Baseline Week 8 Week 96 Primary endpoint Primary Objective: Assess non-inferiority of vs D/C + F/TDF by proportion of patients with VL <5 c/ml at 8 weeks (NI margin %; FDA-Snapshot algorithm) Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/.
BASELINE CHARACTERISTICS QD N=36 Control N=363 Total N=75 Median (IQR) age, years 3 (7 ) 3 (7 ) 3 (7 ) Male, n (%) 38 (87.8) 3 (88.7) 6 (88.3) Median (IQR) log VL, c/ml. (..8).6 (..9).5 (..9) Median (IQR) CD + count, cells/mm 3 6.5 (3 67). (35 59) 53. (333 6) Median (IQR) egfr cr, ml/min (Cockcroft-Gault) 9 (5 35) 8 (3 38) 9 ( 36.5) Genotype at Screening N=36 N=36 N=73 primary PI RAMs 7 (.9) 8 (.) 5 (.) NRTI RAMs 8 (5.) 6 (.) 3 (.7) NNRTI RAMs 55 (5.) 63 (7.) 8 (6.3) Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/. VIROLOGIC OUTCOME AT WEEK 8 Proportion of patients (%) 8 6 9.% (n=33) Virologic VL 5 c/ml No virologic data - -8-6 - 6 8 response (VL<5 c/ml) Percentage point difference Subgroup analysis by: Age, gender, race, CD (</>), viral load (</>.) similar results. Point estimates favor No development of DRV, primary PI or TDF/TAF RAMs. One patient () developed M8I/V conferring resistance to FTC p-value for non-inferiority at % margin 88.% (n=3).% (n=6) Non-inferior to Control Lower Bound 95% CI > % (N=36) 3.3% (n=).% (n=5) Control (N=363) 8.3% (n=3) Stratified difference (95% CI) ( control) Favours control Favours.7 -.6 7. p< Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/.
SAFETY Incidence, n (%) Incidences and types of laboratory abnormalities were similar in both treatment arms being mostly Grade or Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/. QD N=36 3 (86.) 9 (5.) 7 (.7) Control N=363 37 (8.6) (6.) (5.8) AE, any grade grade 3 AE serious AE Deaths AEs Leading to Discontinuation AE 7 (.9) 6 (.) Rash (n=6) Rash/erythema (n=7) Diarrhoea (n=) Diarrhoea (n=) Toxic skin eruption (n=) SJS (n=) Bone marrow oedema (n=) Increased Beta macroglobulin (n=) Arthralgia (n=) Neoplasms (n=) MEAN CHANGES IN EGFR THROUGH 8 WEEKS Estimated GFR based on Serum Creatinine a Estimated GFR based on Serum Cystatin C a change from baseline in egfr (ml/min/.73m ) (N=3) Control (N=33) 8 p<.* 8 6 9 33 37 5 9-8 - (N=337) Control (N=39) 8 8 6 9 33 37 5 9 p=.* -8 - a. Based on serum levels and CKD-EPI formula * p value for difference estimated using ANCOVA, including treatment as a factor and baseline egfr as a covariate Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/.
MEAN CHANGES IN PROTEINURIA THROUGH 8 WEEKS Urinary protein:creatinine Urinary albumin:creatinine - - -3 Control BL 66.3 (3.66) 77.67 (6.5) -.3 -. p=.33 5-5 -5-5 Control BL.38 (.57) 7.9 (5.7) -.5 -.58 p=.3 * Retinol binding protein:creatinine β--microglobulin:creatinine p<. * p<. * 6. 5 837.63 6.8 change (μg/g) 5-5 -.58 BL.66 (7.) 86.73 (7.66) BL 8.5 (.36) 379.5 (76.) Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/. MEAN % CHANGES IN BMD THROUGH 8 WEEKS (N=96) Control (N=85) % change from baseline in BMD p<. p=. - -.7 -.3 - -3 -. -3. 8 - - -3 P<. p<..3. -.7 -.7 8 Control Control 3% decrease 7.%.%.5%.7% 3% increase.5%.7%.5%.% Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/.
FASTING LIPID LEVELS AT BASELINE AND WEEK 8 5 baseline Week 8 Control baseline Control Week 8 p=.36 Median lipid value (mg/dl) 5 5 63 p<. 7 6 96 p<. 97 p<. 97 p=. 3 95 3.8. 3.8 3.9 3 TC:HDL-C ratio Total cholesterol LDL-C HDL-C Triglycerides TC:HDL-C ratio During treatment, lipid-lowering drugs started by 6 (.7%) vs (.6%) patients (p=.8) Orkin C, et al; 6th EACS, Milan, Italy, October 5-7, 7; Abst. PS8/.