Trial Outcomes & Findings for Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis (NCT NCT02114151)

NCT ID: NCT02114151

Last Updated: 2016-04-04

Results Overview

Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (\<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the actual end of treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 103 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2016-04-04

Participant Flow

A total of 147 participants from the United States and Canada were Screened and 103 were enrolled into the study. All 103 participants who received at least 1 dose of study drug and so were included in intent to treat (ITT) population.

Participant milestones

Measure	Simeprevir Plus Sofosbuvir Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Overall Study STARTED	103
Overall Study COMPLETED	96
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Simeprevir Plus Sofosbuvir Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Overall Study Death	1
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	5

Baseline Characteristics

Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis

Baseline characteristics by cohort

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication.

Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the actual end of treatment.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Actual End of Treatment (EOT)	83.5 Percentage of Participants Interval 75.8 to 91.1

SECONDARY outcome

Timeframe: Week 16

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication.

Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the actual end of treatment.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Actual End of Treatment (EOT)	86.4 Percentage of Participants Interval 79.3 to 93.5

SECONDARY outcome

Timeframe: Week 36

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication.

Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 24 weeks after the actual end of treatment.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Actual End of Treatment (EOT)	82.5 Percentage of Participants Interval 74.7 to 90.3

SECONDARY outcome

Timeframe: Week 2, 4 and End of Treatment (Week 12)

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here 'n' specifies those participants who were evaluated for this outcome measure at given time point.

On-treatment virologic response was determined by HCV RNA results satisfying a specified threshold. <LLOQ undetectable was considered as threshold at any time point. The LLOQ value is 25 IU/mL. EOT=End of Treatment.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With On-treatment Virologic Response Week 2: < 100 IU/mL (n=102)	90.2 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 2: < 25 IU/mL (n=102)	68.6 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 2: < 25 IU/mL Detectable (n=102)	44.1 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 2: < 25 IU/mL Undetectable (n=102)	24.5 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 4: < 100 IU/mL (n=102)	99.0 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 4: < 25 IU/mL (n=102)	99.0 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 4: < 25 IU/mL Detectable (n=102)	15.7 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response Week 4: < 25 IU/mL Undetectable (n=102)	83.3 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response EOT (Week 12): < 100 IU/mL (n=103)	97.1 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response EOT (Week 12): < 25 IU/mL (n=103)	97.1 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response EOT (Week 12): < 25 IU/mL Detectable (n=103)	0 Percentage of Participants
Percentage of Participants With On-treatment Virologic Response EOT (Week 12): < 25 IU/mL Undetectable (n=103)	97.1 Percentage of Participants

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-treat (ITT) population included all randomized participants who took at least one dose of investigational drug.

On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With On-treatment Failure	2.9 Percentage of Participants

SECONDARY outcome

Timeframe: Up to End of Treatment (Week 12)

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication.

Viral breakthrough was defined as confirmed greater than (>) 1 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA < LLOQ (25 IU/mL).

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=103 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With Viral Breakthrough	1.9 Percentage of Participants

SECONDARY outcome

Timeframe: During the Follow-up (Week 24)

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.

Viral relapse was defined as participants who did not achieve SVR12 and had HCV RNA < LLOQ (25 IU/mL) undetectable at EOT and had HCV RNA >= LLOQ (25 IU/mL) during the follow-up period.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=99 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With Viral Relapse	13.1 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 4, Week 12 and Follow-Up Week 12

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.

The HCV-SIQv4 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.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=98 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12 Baseline (n=98)	17.4 Units on a Scale Standard Error 1.47
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12 Change at Week 4 (n=96)	-4.9 Units on a Scale Standard Error 1.23
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12 Change at Week 12 (n=89)	-4.7 Units on a Scale Standard Error 1.39
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12 Change at Follow-up Week 12 (n=94)	-5.8 Units on a Scale Standard Error 1.36

SECONDARY outcome

Timeframe: Baseline, Week 12, Follow-up Week 12 and 24

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.

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 7-point 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.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=96 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24 Baseline (n=96)	3.4 Units on a Scale Standard Error 0.18
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24 Change at Week 12 (n=86)	-0.4 Units on a Scale Standard Error 0.18
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24 Change at Follow-up Week 12 (n=92)	-0.6 Units on a Scale Standard Error 0.16
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24 Change at Follow-up Week 24 (n=86)	-0.8 Units on a Scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline, Week 12, Follow-up Week 12 and 24

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.

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

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=96 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Follow-up Week 12: No Depression (n=94)	79.8 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Baseline: No Depression (n=96)	67.7 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Baseline: Mild to Moderate Depression (n=96)	16.7 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Baseline: Severe Depression (n=96)	15.6 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Week 12: No Depression (n=88)	77.3 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Week 12: Mild to Moderate Depression (n=88)	15.9 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Week 12: Severe Depression (n=88)	6.8 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Follow-up Week12:Mild to Moderate Depression(n=94)	6.4 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Follow-up Week 12: Severe Depression (n=94)	13.8 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Follow-up Week 24: No Depression (n=88)	79.5 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Follow-up Week24:Mild to Moderate Depression(n=88)	10.2 Percentage of Participants
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) Follow-up Week 24: Severe Depression (n=88)	10.2 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Follow-up Week 12 and 24

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.

The EQ-5D questionnaire was a brief, generic health-related quality of life (HRQOL) assessment that could also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assessed 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).

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=96 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24 Baseline (n=96)	70.1 Units on a Scale Standard Error 2.17
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24 Change at Follow-up Week 12 (n=92)	9.8 Units on a Scale Standard Error 1.90
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24 Change at Follow-up Week 24 (n=86)	9.5 Units on a Scale Standard Error 1.75

SECONDARY outcome

Timeframe: Baseline, Day 3, Week 1, 2, 3, 4, 8, 12, Follow-up Week 4, 12 and 24

Population: Intent-to-treat (ITT) population included all enrolled participants who took at least 1 dose of investigational medication. Here, "N" (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.

Sequencing of the HCV nonstructural protein 3/4A (NS3/4A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. Sequencing data is available for 16 participants.

Outcome measures

Measure	Simeprevir Plus Sofosbuvir n=16 Participants Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Number of Participants Not Achieving SVR Showing Emerging Mutation at Time of Failure in HCV NS3/4A Sequence and NS5B up to Follow-up Week 24 HCV NS3	13 Participants
Number of Participants Not Achieving SVR Showing Emerging Mutation at Time of Failure in HCV NS3/4A Sequence and NS5B up to Follow-up Week 24 NS5B	0 Participants

Adverse Events

Simeprevir Plus Sofosbuvir

Serious events: 5 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	Simeprevir Plus Sofosbuvir n=103 participants at risk Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
Infections and infestations Cellulitis	0.97% 1/103 • Baseline up to End of Treatment (Week 36)
Infections and infestations Sepsis	0.97% 1/103 • Baseline up to End of Treatment (Week 36)
Injury, poisoning and procedural complications Limb injury	0.97% 1/103 • Baseline up to End of Treatment (Week 36)
Injury, poisoning and procedural complications Road traffic accident	0.97% 1/103 • Baseline up to End of Treatment (Week 36)
Blood and lymphatic system disorders Anaemia	0.97% 1/103 • Baseline up to End of Treatment (Week 36)
General disorders Non-cardiac chest pain	0.97% 1/103 • Baseline up to End of Treatment (Week 36)

Other adverse events

Measure	Simeprevir Plus Sofosbuvir n=103 participants at risk Participants received simeprevir 150 milligram (mg) in combination with sofosbuvir 400 mg once daily for 12 weeks.
General disorders Fatigue	20.4% 21/103 • Baseline up to End of Treatment (Week 36)
Nervous system disorders Headache	20.4% 21/103 • Baseline up to End of Treatment (Week 36)
Gastrointestinal disorders Nausea	10.7% 11/103 • Baseline up to End of Treatment (Week 36)
Gastrointestinal disorders Constipation	7.8% 8/103 • Baseline up to End of Treatment (Week 36)
Psychiatric disorders Insomnia	6.8% 7/103 • Baseline up to End of Treatment (Week 36)
Psychiatric disorders Depression	5.8% 6/103 • Baseline up to End of Treatment (Week 36)
Skin and subcutaneous tissue disorders Pruritus	9.7% 10/103 • Baseline up to End of Treatment (Week 36)

Additional Information

Associate Director

Janssen Infectious Diseases - Diagnostics BVBA

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER