Trial Outcomes & Findings for Efficacy and Safety of Elbasvir (MK-8742) + Grazoprevir (MK-5172) in Treatment-Naïve/Treatment-Experienced (TN/TE) French Participants With Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection (MK-5172-096) (NCT NCT03111108)
NCT ID: NCT03111108
Last Updated: 2020-06-09
Results Overview
The percentage of participants to achieve SVR12 was determined for each arm (SVR12 was defined as HCV ribonucleic acid \[RNA\] \< lower limit of quantification \[LLOQ\] at 12 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
117 participants
Primary outcome timeframe
12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24)
Results posted on
2020-06-09
Participant Flow
Adult male and female participants with chronic hepatitis C virus (HCV) genotype 4 (GT4) infection were enrolled at 12 study centers in France.
Participant milestones
| Measure |
Arm 1: EBR/GZR for 8 Weeks
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received elbasvir/grazoprevir (EBR/GZR) fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Overall Study
STARTED
|
53
|
64
|
|
Overall Study
COMPLETED
|
52
|
63
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Arm 1: EBR/GZR for 8 Weeks
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received elbasvir/grazoprevir (EBR/GZR) fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Elbasvir (MK-8742) + Grazoprevir (MK-5172) in Treatment-Naïve/Treatment-Experienced (TN/TE) French Participants With Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection (MK-5172-096)
Baseline characteristics by cohort
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR FDC (50 mg/100 mg) for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
Total
n=117 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.5 Years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
56.0 Years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
54.0 Years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
20 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 weeks after completing study treatment (Arm 1: Week 20 / Arm 2: Week 24)Population: All randomized participants who received ≥1 dose of study treatment are included.
The percentage of participants to achieve SVR12 was determined for each arm (SVR12 was defined as HCV ribonucleic acid \[RNA\] \< lower limit of quantification \[LLOQ\] at 12 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.
Outcome measures
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After End of Treatment (SVR12)
|
94.3 Percentage of Participants
Interval 84.3 to 98.8
|
95.3 Percentage of Participants
Interval 86.9 to 99.0
|
PRIMARY outcome
Timeframe: Up to 14 weeksPopulation: All randomized participants who received ≥1 dose of study treatment are included, classified according to treatment duration actually received.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Outcome measures
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Number of Participants With ≥ 1 Adverse Events (AEs)
|
33 Participants
|
46 Participants
|
PRIMARY outcome
Timeframe: Up to Study Week 12Population: All randomized participants who received ≥1 dose of study treatment are included, classified according to treatment duration actually received.
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Outcome measures
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Number of Participants Who Discontinued From Study Treatment Due to an AE
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 weeks after completing study treatment (Arm 1: Week 32 / Arm 2: Week 36)Population: All randomized participants who received ≥1 dose of study treatment are included.
The percentage of participants to achieve SVR24 was determined for each arm (SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after the end of all study therapy). Plasma HCV RNA was measured using the COBAS™ AmpliPrep/COBAS™ TaqMan HCV Test, v2.0®, which has a LLOQ of 15 IU/mL.
Outcome measures
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After End of Treatment (SVR24)
|
94.3 Percentage of Participants
Interval 84.3 to 98.8
|
93.8 Percentage of Participants
Interval 84.8 to 98.3
|
SECONDARY outcome
Timeframe: Day 1Population: All randomized participants with baseline sequencing data for NS3 are included.
Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS3 gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a direct-acting antiviral (DAA) and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS3.
Outcome measures
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=51 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=59 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR
GT4
|
5 Participants
|
6 Participants
|
|
Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR
GT4D
|
3 Participants
|
3 Participants
|
|
Prevalence of Baseline NS3 Resistance-Associated Substitutions (RASs) to EBR or GZR
GT4-Other
|
6 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: Day 1Population: All randomized participants with baseline sequencing data for NS5A are included.
Blood samples for viral resistance assays were collected at Baseline (Day 1) and analyzed for substitutions in the NS5A gene region. Results are pooled for all participants with baseline sequencing data available, and the number of participants with RASs is reported according HCV genotype. Resistance-associated substitutions are defined as amino acid substitutions that confer reduced susceptibility to a DAA and may contribute to virologic failure. The prevalence of baseline substitutions in participants infected with HCV GT4 subtypes was assessed by evaluating amino acid substitutions in NS5A.
Outcome measures
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 Participants
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=63 Participants
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Prevalence of Baseline NS5A RASs to EBR or GZR
GT4
|
3 Participants
|
2 Participants
|
|
Prevalence of Baseline NS5A RASs to EBR or GZR
GT4D
|
10 Participants
|
16 Participants
|
|
Prevalence of Baseline NS5A RASs to EBR or GZR
GT4-Other
|
13 Participants
|
21 Participants
|
Adverse Events
Arm 1: EBR/GZR for 8 Weeks
Serious events: 2 serious events
Other events: 27 other events
Deaths: 0 deaths
Arm 2: EBR/GZR for 12 Weeks
Serious events: 2 serious events
Other events: 38 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 participants at risk
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 participants at risk
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Infections and infestations
Post procedural infection
|
1.9%
1/53 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
0.00%
0/64 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
1.9%
1/53 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
0.00%
0/64 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/53 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
1.6%
1/64 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Nervous system disorders
Cerebellar stroke
|
0.00%
0/53 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
1.6%
1/64 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
Other adverse events
| Measure |
Arm 1: EBR/GZR for 8 Weeks
n=53 participants at risk
Treatment-naïve HCV GT4 participants with stage 0-2 fibrosis (F0-F2) received EBR/GZR fixed dose combination (FDC) \[50 mg/100 mg\] for 8 weeks, followed by 24 weeks of follow-up.
|
Arm 2: EBR/GZR for 12 Weeks
n=64 participants at risk
Treatment-naïve HCV GT4 participants with F0-F2 stage fibrosis, treatment-naïve participants with F3-F4 stage fibrosis, and treatment-experienced participants with F0-F4 stage fibrosis received EBR/GZR FDC (50 mg/100 mg) for 12 weeks, followed by 24 weeks of follow-up.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/53 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
6.2%
4/64 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.7%
3/53 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
4.7%
3/64 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Gastrointestinal disorders
Nausea
|
7.5%
4/53 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
6.2%
4/64 • Number of events 5 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
General disorders
Asthenia
|
22.6%
12/53 • Number of events 12 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
21.9%
14/64 • Number of events 14 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
General disorders
Fatigue
|
1.9%
1/53 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
6.2%
4/64 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Infections and infestations
Bronchitis
|
5.7%
3/53 • Number of events 3 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
1.6%
1/64 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Infections and infestations
Influenza
|
3.8%
2/53 • Number of events 2 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
6.2%
4/64 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Infections and infestations
Nasopharyngitis
|
1.9%
1/53 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
7.8%
5/64 • Number of events 5 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.7%
3/53 • Number of events 3 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
1.6%
1/64 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
3/53 • Number of events 3 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
1.6%
1/64 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Nervous system disorders
Dizziness
|
5.7%
3/53 • Number of events 4 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
1.6%
1/64 • Number of events 1 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Nervous system disorders
Headache
|
17.0%
9/53 • Number of events 10 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
25.0%
16/64 • Number of events 16 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Psychiatric disorders
Insomnia
|
3.8%
2/53 • Number of events 2 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
7.8%
5/64 • Number of events 6 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.8%
2/53 • Number of events 2 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
6.2%
4/64 • Number of events 5 • Up to 36 weeks
All participants who received ≥1 dose of study medication are included.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation.
- Publication restrictions are in place
Restriction type: OTHER