F/C AETC Faculty HIV/HCV Thursday May 8, 2014 | 1:30- 2:30pm (EDT) Facilitator/ Presenter Dushyantha T. Jayaweera, MD, MRCOG (UK), FACP University of Miami.

Slides:

Advertisements

Similar presentations

F/C AETC Faculty HIV/HCV Thursday, June 26, 2014 | 1:30-2:30pm (EDT) Facilitator/Didactic Presenter Dushyantha T. Jayaweera MD, MRCOG (UK), FACP University.

Advertisements

Hepatitis web study Hepatitis web study Hepatitis web study Hepatitis web study Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir +/- RBV in GT1 PEARL-III.

Hepatitis web study Hepatitis web study 3D (Paritaprevir-Ritonavir-Ombitasvir + Dasabuvir) +/- RBV in GT1 PEARL-III and PEARL-IV Phase 3 Treatment Naïve.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir +/- Ribavirin in HCV Genotype 1 ION-1 Phase 3 Treatment Naïve Source: Afdhal N, et al. N.

Hepatitis web study Hepatitis web study Hepatitis web study Hepatitis web study Ombitasvir-Paritaprevir-Ritonavir and Dasabuvir + RBV in GT1 SAPPHIRE-I.

Hepatitis web study Hepatitis web study Ledipasvir-Sofosbuvir for 8 or 12 weeks in HCV GT1 ION-3 Phase 3 Treatment Naïve Kowdley K, et al. N Engl J Med.

Hepatitis web study Hepatitis web study Simeprevir + Sofosbuvir +/- Ribavirin in Genotype 1 COSMOS Trial Phase 2a, Treatment Naïve and Treatment Experienced.

VALENCE SOF + RBV Not randomised Open label* ≥ 18 years Chronic HCV infection Genotype 2 or 3 HCV RNA ≥ 10,000 IU/ml Treatment naïve or prior IFN-based.

Hepatitis web study Hepatitis web study Telaprevir BID versus q8 in Treatment Naïve GT-1 OPTIMIZE (Study C211) Phase 3 Treatment Naïve Buti M, et al. Gastroenterology.

ATOMIC  Design  Objective –SVR 24 by ITT-analysis, detection of a 30% or 25% difference between two treatment groups, 2-sided significance level of 5%,

LDV/SOF 90/400 mg qd Non-randomised Open-label N = 21 W12 SVR 12 NIAID SYNERGY GT4 Kohli A. Lancet Infect Dis 2015; Juky 15, ePub ahead of print ≥ 18 years.

OBV/PTV/r Open label years Chronic HCV infection Genotype 1b Treatment-naïve or failure to PEG-IFN + RBV HCV RNA > 10,000 IU/ml Without or with cirrhosis*

Hepatitis web study Hepatitis web study Daclatasvir-Asunaprevir-Beclabuvir in Genotype 1 Cirrhotics UNITY-2 Study Phase 3 Treatment-Naïve and Treatment-Experienced.

COSMOS SOF + SMV + RBV SOF + SMV Randomisation 2 : 1 : 2 : 1* Open-label * Randomisation was stratified on genotype (1a or 1b) in both cohorts, IL28B in.

Hepatitis web study Hepatitis web study Daclatasvir + Sofosbuvir in Genotype 3 ALLY-3 Study Phase 3 Treatment-Naïve and Treatment-Experienced Nelson DR,

NS5A and polymerase inhibitors Mark Sulkowski, MD Professor of Medicine Johns Hopkins University Baltimore Maryland

Randomisation* 2 : 1 Double blind *Randomisation was stratified on genotype (1a or 1b or other) and IL28B genotype (CC, CT or TT) N = 133 N = 260 W24W48.

FUSION  Design  Objectives –SVR ≥ 20% compared with historical control of 25%, 97% power –Difference of SVR > 20% between the 2 groups, 82% power SOF.

FISSION  Design  Objective –Non inferiority of SOF + RBV : SVR 12 (2-sided significance level of 5%, lower margin of the 95% CI for the difference =

No HBV or HIV co-infection

SOF + PEG-IFN  -2a + RBV Open-label Single arm ≥ 18 years Chronic HCV infection Genotype 1, 4, 5 or 6 Treatment-naïve HCV RNA ≥ 10,000 IU/ml Compensated.

SMV SOF 400 Open-label OPTIMIST-2 Study: SMV + SOF for genotype 1 and cirrhosis W12  Objective –Superiority of SVR 12 (HCV RNA historical control.

SMV 150 mg QD + SOF 400 mg QD Randomisation 1 : years HCV genotype 1 Naïve or pre-treated with IFN-based regimen No cirrhosis HCV RNA ≥

OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + placebo Randomisation* Partial blind years Chronic HCV infection Genotype 1 Treatment-naïve HCV RNA > 10,000.

ION-4  Design LDV/SOF Open-label ION-4 Study: LDV/SOF in HIV co-infection W12 ≥ 18 years Chronic HCV infection Genotype 1 or 4 HCV RNA ≥ 10,000 IU/ml.

ARV-trial.com C-SWIFT Study: grazoprevir/elbasvir + SOF in genotypes 1 or 3, with or without cirrhosis Randomisation 1 : 1 Open-label Design W4 W6 W8.

ION-1  Design LDV/SOF LDV/SOF + RBV Randomisation* 1 : 1 : 1 : 1 Open-label ION-1 Study: LDV/SOF + RBV for genotype 1 W24W12 ≥ 18 years Chronic HCV infection.

OBV/PTV/r Placebo Randomisation** 2 : years Chronic HCV Genotype 1b HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated, no prior failure with DAA Without.

SOLAR-2 LDV/SOF + RBV Randomisation of the 7 groups 1 : 1 Open-label SOLAR-2 Study: LDV/SOF + RBV in decompensated and post-liver transplant with genotype.

Hepatitis web study Hepatitis web study Sofosbuvir + RBV in Treatment-Naïve Genotypes 2,3 FISSION Trial* Phase 3 *Note: Published in NEJM in tandem with.

No randomization N = 59 W12W24 Arm B : compensated cirrhosis N = 31 N = 29 Arm C : compensated cirrhosis Arm A : No cirrhosis AGATE-II Study: OBV/PTV/r.

Hepatitis web study Hepatitis web study Sofosbuvir + Peginterferon + Ribavirin in Genotype 2 or 3 LONESTAR-2 Phase 2 Treatment Experienced Lawitz E, et.

> 18 years Chronic HCV infection Genotype 1 Failure (relapse) to 4, 6 or 8 weeks of GZR/EBR + SOF in C-SWIFT Part A Compensated cirrhosis assessed by liver.

SOF/VEL 400/100 mg qd N = 500 N = 100 W12 Placebo > 18 years Chronic HCV infection Genotype 1, 2, 4, 5 or 6 Naïve or pre-treatment with IFN-based regimen.

SOF/VEL 400/100 mg qd N = 250 W24 SOF + RBV W12 * Randomisation was stratified on prior treatment (naïve or experienced) and cirrhosis (yes or no) ** Metavir.

Asselah T. AASLD 2015, Abs. 714 Randomisation 1:1 Open-label years HCV genotype 4 HCV RNA ≥ 1,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV (Part.

Sulkowski M. Lancet 2015;385: C-WORTHY  Design Randomisation* Open-label > 18 years HCV genotype 1, treatment naïve HCV RNA ≥ 10,000 IU/ml No cirrhosis.

 Objective –SVR 12 (HCV RNA < 25 IU/ml), with 95% CI, next observation carried backward DCV + SOF + RBV Randomised* 1:1 Open-label ALLY-3+ study: DCV.

SOF + RBV Randomisation* 1 : 1 : 1 Open-label BOSON Study: SOF + RBV + PEG-IFN for genotypes 2 and 3 ≥ 18 years Chronic HCV infection Genotype 2, treatment-

 Design  Objective –Difference in SVR ≥ 40% between the 2 groups, 99% power SOF + RBV Placebo Randomisation 3 : 1* Double blind HCV infection Genotype.

SAPPHIRE-I Feld JJ. NEJM 2014;370: SAPPHIRE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for genotype 1  Treatment regimens.

LDV/SOF Failure Open-label W24 Chronic HCV infection Genotype 1 Failure to achieve SVR on LDV/SOF-containing regimen Compensated cirrhosis (liver biopsy.

SOF/VEL 400/100 mg qd N = 120 W12 SOF + RBV > 18 years Chronic HCV infection Genotype 2 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis.

Placebo + PR W24 DCV + PR Placebo + PR Yes Dore GJ. Gastroenterology 2015;148: COMMAND GT2/3 COMMAND GT2/3 Study: daclatasvir + PEG-IFN + RBV for.

 Design Randomisation* 2 : 1 Double blind *Randomisation was stratified on genotype (1a vs 1b) and ILB28 genotype (CC or non-CC) N = 134 N = 257 W24W48.

 Design Open-label years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks.

Hepatitis web study Hepatitis web study Elbasvir-Grazoprevir in Treatment-Naïve HCV Genotype 1, 4 or 6 C-EDGE Treatment Naïve (TN) Phase 3 Treatment Naïve.

Hadziyannis SJ et al. EASL Peginterferon alfa-2a (40KD) (PEGASYS ® ) in combination with ribavirin (RBV): efficacy and safety results from a phase.

SOF/VEL 400/100 mg qd N = 106 W12 > 18 years Chronic HCV infection Genotype 1-6 Naïve or pre-treatment with IFN-based regimen Compensated cirrhosis allowed*

No HBV or HIV co-infection

LDV/SOF Randomisation * 1:1 Open-label ≥ 20 years, Japanese Chronic HCV infection Genotype 1 HCV RNA ≥ IU/ml Treatment-naive, or pre-treated Compensated.

eGFR (MDRD) > 50 mL/min

Daclatasvir + Sofosbuvir in Genotype 3 ALLY-3 Study

ARV-trial.com C-CREST study, Part B: uprifosbuvir (MK-3682)/GZR/ruzasvir (MK-8408) fixed-dose combination + RBV for genotypes 1, 2 and 3 - Phase II Randomisation.

Design Randomisation 2 : 1 Double-blind W12 ≥ 18 years, HCV genotype 3

Phase 3 Treatment-Naïve and Treatment-Experienced

Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2

C-BREEZE-2 Study: ruzasvir + uprifosbuvir for 12 weeks in genotype 1-6

SOF/VEL + GS-9857 in genotypes 1-6 Phase II

LEAGUE-1 study: daclatasvir + SMV + RBV for genotype 1

Phase 2 Treatment Naïve Injection Drug Use

Phase 3 Treatment-Naïve and Treatment-Experienced

Ombitasvir + Paritaprevir + Ritonavir +/- Ribavirin in HCV GT4 PEARL-I

Obiettivi e strategie di un

Phase 2b Treatment Naïve and Treatment Experienced

MAGELLAN-3 Study: GLE/PIB + SOF + RBV in patients who failed GLE/PIB

LDV/SOF ± RBV in genotype 3 or 6 – Phase 2

Phase 3 Treatment-Naïve and Treatment-Experienced

Telaprevir + Peginterferon + Ribavirin for GT1 PROVE1 Study

Glecaprevir-Pibrentasvir in Non-Cirrhotic Genotype 2 ENDURANCE-2

Presentation transcript:

F/C AETC Faculty HIV/HCV Thursday May 8, 2014 | 1:30- 2:30pm (EDT) Facilitator/ Presenter Dushyantha T. Jayaweera, MD, MRCOG (UK), FACP University of Miami Case Discussant Patrick Marsh, MD University of South Florida Maribel Gonzalez, RN, ARNP University of South Florida

HIV Case Conference: Highlights from EASL Dushyantha T. Jayaweera MD, MRCOG (UK), FACP Associate Vice Provost for Human Subject Research & Professor of Medicine, University of Miami, Miller School of Medicine, Division of Infectious Diseases Faculty Member, Florida/Caribbean AIDS Education and Training Center

HCV TREATMENT IN TREATMENT NAIVE PATIENTS

SAPPHIRE-I Study: Design ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=473) ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=473) Placebo*(n=158)Placebo*(n=158) Week ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=158) ABT-450/r/ABT-267 qd + ABT-333 bid + RBV bid (n=158) Double-Blind Open-Label Feld J, et al. 49th EASL; London, England; April 9-13, Abst. O60. Phase 3 Study Double-Blind Key eligibility criteria HCV genotype 1 Treatment-naïve No cirrhosis No HIV or HBV

SAPPHIRE-1 Study: Interim Results Virologic relapse: 1.7% 3D regimen + RBV was well-tolerated Discontinuations due to adverse events: 0.6% Most commonly reported adverse events Fatigue Headache Nausea Feld J, et al. 49th EASL; London, England; April 9-13, Abst. O60. Patients (Percentage) SVR12 Rates 3D Regimen + RBV 1a (n=322) 1b (n=151) Overall (n=473) 95% 98% 96% Genotype

ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV bid (n=210) ABT-450/r/ABT-267 qd + ABT-333 bid+ RBV Placebo (n=209) Week Phase 3 Study Double-Blind Placebo-controlled Key eligibility criteria HCV genotype 1 Treatment-naïve No cirrhosis No HIV or HBV PEARL-III Study: Design Ferenci P, et al. 49th EASL; London, England; April 9-13, Abst. P1299.

Pearl-III Study: SVR12 and Virologic Failure Rates 3D Regimen + RBV Ferenci P, et al. 49th EASL; London, England; April 9-13, Abst. P1299. Patients (Percentage) No RBV (n=209) With RBV (n=210) 99% SVR12 0% No RBV (n=209) 0.5% With RBV (n=210) Virologic Failure

Pearl-III Study: Safety Results 3D regimen + RBV was well tolerated Discontinuations due to adverse events With RBV: 0% No RBV: 0% Most commonly reported adverse events Headache Fatigue Ferenci P, et al. 49th EASL; London, England; April 9-13, Abst. P1299.

ION-1 Study: Design GT 1 HCV treatment-naïve patients in Europe and USA Broad inclusion criteria Targeted 20% enrollment of patients with cirrhosis No upper age or BMI limit Platelet count ≥50,000/mm 3, no neutrophil minimum 865 patients randomized 1:1:1:1 across four arms Stratified by HCV subtype (1a or 1b) and cirrhosis Mangia A, et al. 49th EASL; London, England; April 9-13, Abst. O164. Wk 0 Wk 12Wk 36Wk 24 LDV/SOF SVR12 LDV/SOF + RBV LDV/SOF LDV/SOF + RBV SVR12

179/18032/34178/18433/33181/18431/33179/18136/36 12 Weeks24 Weeks LDV/SOF + RBV LDV/SOF SVR12 (Percentage) Absence of Cirrhosis Cirrhosis ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis Error bars represent 95% confidence intervals. Mangia A, et al. 49th EASL; London, England; April 9-13, Abst. O164.

179/18032/34178/18433/33181/18431/33179/18136/36 12 Weeks24 Weeks LDV/SOF + RBV LDV/SOF SVR12 (Percentage) Absence of CirrhosisCirrhosis ION-1 Study: SVR12 - Absence of Cirrhosis vs Cirrhosis Error bars represent 95% confidence intervals. Mangia A, et al. 49th EASL; London, England; April 9-13, Abst. O164.

ION-3 Study: Design GT 1 treatment-naïve patients without cirrhosis Broad inclusion criteria No upper age or BMI limit Opiate substitution therapy allowed 647 patients randomized 1:1:1 across three arms Stratified by HCV subtype (1a or 1b) LDV/SOF LDV/SOF + RBV SVR12 Kowdley K, et al. 49th EASL; London, England; April 9-13, Abst. O56. Wk 0 Wk 12Wk 36Wk 24

Error bars represent 95% confidence intervals. Kowdley K, et al. 49th EASL; London, England; April 9-13, Abst. O56. ION-3 Study Results – Non-Inferiority Comparison 201/216202/215206/216 p= Weeks12 Weeks LDV/SOF + RBVLDV/SOF SVR12 (Percentage)

Study Design: MK-5172 (100 mg QD) + MK-8742 (50 mg QD) ± RBV in 253 Pte n = 31 Follow-up D1TW12SVR12TW4TW8 TN + Cirrhosis n=123 TN + Cirrhosis n=123 PR-Nulls ± Cirrhosis n=130 PR-Nulls ± Cirrhosis n=130 SVR24TW18FU8FU4 Follow-up No RBV + RBV No RBV + RBV No RBV + RBV Follow-up n = 29 n = 32 n = 31 n = 32 n = 33 n = 32 Lawitz E, et al. 49th EASL; London, England; April 9-13, Abst. O61. No RBV + RBV No RBV + RBV No RBV + RBV

* 30 31* TW4 TW12 FU4/8 Breakthrough Relapse Discontinuation Efficacy of MK MK-8742 ± RBV in Treat-Naïve Pte + Cirrhosis:12W vs18W *Excludes patients who have not yet reached the FU4 time point 12 week arms include 97% of FU8 results Lawitz E, et al. 49th EASL; London, England; April 9-13, Abst. O61.

Discussion