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Report for Clinical Trial NCT02114177

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of a 12- or 8-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naïve and -Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection Without Cirrhosis

The purpose of the study is to evaluate the efficacy and safety of a treatment regimen of 12 weeks or 8 weeks of simeprevir in combination with sofosbuvir in chronic hepatitis C virus (HCV) genotype 1 infected men and women without cirrhosis who are HCV treatment-naïve or treatment-experienced.

NCT02114177 Hepatitis C Virus Infection
MeSH: Infection Communicable Diseases Hepatitis A Hepatitis C Hepatitis Liver Cirrhosis Fibrosis Virus Diseases
HPO: Cirrhosis Hepatic fibrosis Hepatitis

4 Interventions

Name: Simeprevir

Description: 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.

Type: Drug

Arm 1 (Simeprevir/Sofosbuvir)

Name: Simeprevir

Description: 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2

Type: Drug

Arm 2 (Simeprevir/Sofosbuvir)

Name: Sofosbuvir

Description: 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.

Type: Drug

Arm 1 (Simeprevir/Sofosbuvir)

Name: Sofosbuvir

Description: 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.

Type: Drug

Arm 2 (Simeprevir/Sofosbuvir)


Primary Outcomes

Description: Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the actual end of study drug treatment.

Measure: Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)

Time: 12 weeks after the end of treatment (EOT) (Week 20 or Week 24)

Secondary Outcomes

Description: Participants considered to have achieved SVR4, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 4 weeks after the actual end of study drug treatment.

Measure: Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)

Time: 4 weeks after the end of treatment (EOT) (Week 12 or Week 16)

Description: Participants considered to have achieved SVR24, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 24 weeks after the Actual end of study drug treatment.

Measure: Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)

Time: 24 weeks after the end of treatment (EOT) (Week 32 or Week 36)

Description: Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. Measure: Percentage of Participants Achieving a On-treatment Virologic Response

Time: Day 14, Day 28, End of treatment (Week 8 or Week 12)

Description: Percentage of participants with greater than 1 log10 IU/mL increase in plasma Hepatitis C virus ribonucleic acid level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL.

Measure: Percentage of Participants With Viral Breakthrough

Time: Up to Week 24

Description: Percentage of participants who did not achieve sustained virologic response 12, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase.

Measure: Percentage of Participants With Viral Relapse

Time: Up to Week 24

Description: HCVSIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively.

Measure: Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)

Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24

Description: The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue.

Measure: Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24

Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24

Description: The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness.

Measure: Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores

Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24

Description: The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening.

Measure: Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale

Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 Q80K

Lower scores indicate worsening.. Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Hepatitis C Virus Infection Infection Communicable Diseases Hepatitis A Hepatitis C Hepatitis Liver Cirrhosis Fibrosis Virus Diseases This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. --- Q80K ---

Lower scores indicate worsening.. Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Hepatitis C Virus Infection Infection Communicable Diseases Hepatitis A Hepatitis C Hepatitis Liver Cirrhosis Fibrosis Virus Diseases This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. --- Q80K --- --- Q80K ---



HPO Nodes


HPO:
Cirrhosis
Genes 164
TTC37 TMEM67 GDF2 ATP7B F5 MPV17 HJV IGF2R SLC40A1 POLG ARHGAP31 CCDC115 ATP8B1 BSCL2 HFE TREX1 TTC37 JAK2 BCS1L TFR2 AGPAT2 ACVRL1 TERC FOS POU2AF1 APOE TYMP SLC30A10 BSCL2 CTC1 NOP10 UROD CAV1 INPP5E NOTCH1 TP53 ENG NHP2 FECH DOCK6 LIPA KRT8 SKIV2L RPGRIP1L SMAD4 PPARG LIPA TFAM NGLY1 TERC RPGRIP1L AP1S1 MARS1 DCDC2 SKIV2L RTEL1 GPC1 PARN BSCL2 ALMS1 TERT KRT18 SERPINA1 GBA TNFSF15 HSD3B7 ATP7B ABCB11 SFTPC GALT GLRX5 USB1 PEX1 HFE ITCH TINF2 ALDOB IL21R AKR1D1 F5 GPR35 SLC25A13 ENG TMEM67 CYP7B1 MPI APC TERC TALDO1 CTNNB1 TERT SLC7A7 NR1H4 GBE1 HSD3B7 JAG1 CASP8 HFE BMP2 HAMP CC2D2A EOGT FARSB COG4 TERT SCARB2 ABCB4 CAVIN1 SMPD1 MUC5B RBPJ TALDO1 PIGA AXIN1 TCF4 NPM1 COG4 WRAP53 AP1B1 IL12A LBR JAK2 ASS1 TINF2 DKC1 PHKG2 NPHP3 TRMT5 DKC1 FAH SPIB PHKG2 AGPAT2 DGUOK HBB MST1 ATP6AP1 COG6 ABHD5 PHKA2 SLC40A1 PPARG PDGFRL ACVRL1 DLL4 SLC30A10 IL12RB1 AMACR KRT18 IRF5 SFTPA2 IFT43 MET PIK3CA TREX1 MMEL1 KRT8 PPARG RRM2B TERT NHP2 CC2D2A POLG TNPO3
Hepatic fibrosis
Genes 140
CSPP1 TTC37 DYNC2H1 BBS9 TMEM67 MET IFT122 DZIP1L TMEM67 SLC40A1 WDPCP ARHGAP31 ABCB4 TTC37 GPD1 WDR35 NPHP3 POU2AF1 BBS10 SDCCAG8 C8ORF37 IQCB1 DLL4 PLIN1 BBS1 WDPCP SLC25A13 CEP290 NOP10 INPP5E NOTCH1 SCYL1 PTRH2 DOCK6 TMEM67 BBS7 CC2D2A SKIV2L RPGRIP1L DCDC2 TCTN2 LIPA TMEM67 IFT172 PMM2 NPHP3 RPGRIP1L CTNNB1 AP1S1 PKHD1 WDR35 GPC1 TTC8 NEK1 B9D1 PMM2 TNFSF15 RPGRIP1 NPHP1 BBIP1 INSR FADD INVS OFD1 CCDC28B PEX1 MKS1 PNPLA6 NEK8 CC2D2A LZTFL1 INPP5E RPGRIP1L ANKS6 GPR35 NPHP4 TMEM67 CEP290 MPI TMEM231 IFT80 MPI ARL6 AGL WDR60 CEP55 ASL ALG9 CC2D2A EOGT BBS2 MKKS IFT27 GLIS3 BBS5 INSR CEP290 TRIM32 ABCD3 TRAF3IP1 TMEM107 SDCCAG8 BBS1 DOLK MKS1 RBPJ TALDO1 TCF4 IL12A NPHP1 NHP2 WDR19 TMEM67 HJV HAMP TRAF3IP1 CYP7B1 NPHP3 SPIB PHKG2 IFT140 DGUOK MST1 B9D2 PHKA2 SLC40A1 WDR34 BBS4 PKHD1 TMEM216 SCYL1 DLL4 CEP164 IL12RB1 IRF5 MMEL1 BBS12 IFT172 CC2D2A TNPO3
Hepatitis
Genes 90
CD247 CTNNB1 ATP7B CASP10 PIEZO1 GUSB BLNK SHPK CYP7A1 IL17RA IGF2R CASP8 SH2D1A SLC25A15 BTK BTK C4B CD79B VPS33B XIAP SERPINA1 PIK3R1 GLIS3 POU2AF1 CIITA FOXP3 TPP2 RFX5 CIITA RASGRP1 RFXANK SLC25A15 AXIN1 TCF4 CD3D TP53 IL12A PRKCD CD40LG BTK IGHM IL17RC ALMS1 TRAF3IP2 KRT8 FAS LRRC8A FAS IL17F XIAP SPIB C1S RFX5 RFXAP MST1 TTC7A COG8 SKIV2L VIPAS39 IGLL1 PDGFRL TNFSF15 HSD3B7 CD3E AMACR ATP7B FASLG RFXANK IL12RB1 TCF3 CD79A KRT18 IRF5 MET PIK3CA MMEL1 ITCH TBX19 IL21R AIRE RFXAP TTC7A CLEC7A GPR35 ATP7A CYP7B1 STAT1 PGM1 APC TNPO3