Trial Outcomes & Findings for Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin in Participants With Chronic Hepatitis C Who Failed Prior Direct-Acting Antiviral Therapy (MK-5172-048) (NCT NCT02105454)
NCT ID: NCT02105454
Last Updated: 2018-09-24
Results Overview
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, \<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
79 participants
Primary outcome timeframe
Up to 24 weeks
Results posted on
2018-09-24
Participant Flow
Following 12 weeks of treatment with grazoprevir (GZR), elbasvir (EBR) and ribavirin (RBV), participants were followed-up for an additional 24 weeks.
Participant milestones
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Overall Study
STARTED
|
79
|
|
Overall Study
COMPLETED
|
78
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Study of Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin in Participants With Chronic Hepatitis C Who Failed Prior Direct-Acting Antiviral Therapy (MK-5172-048)
Baseline characteristics by cohort
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=79 Participants
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Age, Continuous
|
54.4 Years
STANDARD_DEVIATION 9.6 • n=93 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Up to 24 weeksPopulation: Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
SVR12 is defined as participants having hepatitis C virus ribonucleic acid (HCV RNA) level lower than the limit of quantification (LLoQ, \<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy.
Outcome measures
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=70 Participants
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Percentage of Participants Achieving Sustained Virologic Response (SVR) at 12 Weeks After the End of All Study Therapy (SVR12)
|
97.1 Percentage of participants
Interval 90.1 to 99.7
|
PRIMARY outcome
Timeframe: Up to 40 weeks (from Day 1 [post-dose] through 24 [-12/+4] weeks following last dose of study drug)Population: All participants as treated population defined as all participants who received at least one dose of study medication.
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Outcome measures
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=79 Participants
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Percentage of Participants Experiencing Adverse Events
|
79.7 Percentage of participants
Interval 69.2 to 88.0
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: All participants as treated population defined as all participants who received at least one dose of study medication.
Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Outcome measures
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=79 Participants
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Percentage of Participants Discontinuing Study Drug Due to an Adverse Event
|
1.3 Percentage of participants
Interval 0.0 to 6.9
|
SECONDARY outcome
Timeframe: Up to 24 weeksPopulation: Per protocol population excludes participants due to important deviations from the protocol that may substantially affect the results of the primary and key secondary efficacy endpoints.
SVR12 is defined as participants having HCV RNA level lower than the LLoQ (\<15 IU/mL in plasma), either target detected and unquantifiable or undetectable 12 weeks after the end of all study therapy. Prior DAA therapy regimen included boceprevir, telaprevir, simeprevir, or sofosbuvir taken concomitantly with peginterferon and ribavirin. Below categories specify with our without resistance-associated variants (RAVs) of the hepatitis C virus.
Outcome measures
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=70 Participants
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Boceprevir with signature baseline RAVs, n=9
|
88.9 Percentage of participants
Interval 51.8 to 99.7
|
|
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Boceprevir without signature baseline RAVs, n=16
|
100.0 Percentage of participants
Interval 79.4 to 100.0
|
|
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Telaprevir with signature baseline RAVs, n=18
|
94.4 Percentage of participants
Interval 72.7 to 99.9
|
|
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Telaprevir without signature baseline RAVs, n=22
|
100.0 Percentage of participants
Interval 84.6 to 100.0
|
|
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Simeprevir with signature baseline RAVs, n=4
|
100.0 Percentage of participants
Interval 39.8 to 100.0
|
|
Percentage of Participants Achieving SVR12 by Prior Direct-acting Antiviral (DAA) Therapy
Simeprevir without signature baseline RAVs, n=1
|
100.0 Percentage of participants
Interval 2.5 to 100.0
|
Adverse Events
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
Serious events: 6 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=79 participants at risk
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Infections and infestations
Appendicitis
|
1.3%
1/79 • Number of events 1 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Infections and infestations
Pharyngitis bacterial
|
1.3%
1/79 • Number of events 1 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Infections and infestations
Urinary tract infection
|
1.3%
1/79 • Number of events 1 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal squamous cell carcinoma
|
1.3%
1/79 • Number of events 1 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.3%
1/79 • Number of events 1 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Gastrointestinal disorders
Inguinal hernia
|
1.3%
1/79 • Number of events 1 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
Other adverse events
| Measure |
GZR 100 mg + EBR 50 mg + RBV for 12 Weeks
n=79 participants at risk
Participants receive grazoprevir 100 mg once per day (QD), elbasvir 50 mg QD, and RBV 800 - 1400 mg total daily dose divided twice per day (based on body weight) for 12 weeks
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.6%
6/79 • Number of events 6 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.3%
5/79 • Number of events 5 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Gastrointestinal disorders
Constipation
|
6.3%
5/79 • Number of events 5 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Gastrointestinal disorders
Diarrhoea
|
7.6%
6/79 • Number of events 11 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Gastrointestinal disorders
Nausea
|
11.4%
9/79 • Number of events 10 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Gastrointestinal disorders
Vomiting
|
5.1%
4/79 • Number of events 4 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
General disorders
Asthenia
|
15.2%
12/79 • Number of events 12 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
General disorders
Fatigue
|
27.8%
22/79 • Number of events 24 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Investigations
Haemoglobin decreased
|
5.1%
4/79 • Number of events 4 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Nervous system disorders
Headache
|
19.0%
15/79 • Number of events 16 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
|
Psychiatric disorders
Insomnia
|
8.9%
7/79 • Number of events 7 • Serious adverse events (SAEs): up to 40 weeks (including 24-week follow-up [-12/+4 weeks]); non-serious adverse events (NSAEs): Up to 14 weeks (including 2-week follow-up)
All participants as treated population included all participants who received at least 1 dose of study medication. MedDRA version 17.1: AEs summarized in the 1st Clinical Study Report (CSR) (through at least 12 weeks of follow-up); MedDRA version 18.0: AEs summarized in the final CSR after study completion (through 24 weeks of follow-up).
|
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. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
- Publication restrictions are in place
Restriction type: OTHER