Efficacy and Safety of Combination Grazoprevir (MK-5172) + Elbasvir (MK-8742) + Ribavirin (RBV) in Genotype 2 Hepatitis C Infection (MK-5172-047)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01932762
• Collaborator: (none)
• Enrollment: 98
• Arms: 4
• Actual Duration (Months): 14.1

Study Details

Study Description

Brief Summary

This is a multi-site, open-label trial evaluating the safety and efficacy of 100 mg of grazoprevir (MK-5172) used in combination with or without 50 mg of elbasvir (MK-8742) and/or ribavirin (RBV) in treating non-cirrhotic treatment-naïve participants with chronic genotype (GT) 2, 4, 5, and 6 hepatitis C infection.

In Part A there is no randomization or stratification; all GT2 participants will be assigned to arm A1. In Part B, all GT2 participants will be assigned to Arm B1 and all participants with GT4, GT5 and GT6 will be randomized in a 1:1 ratio to either Arm 3 or Arm 4 with stratification by genotype.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Grazoprevir; Drug: Elbasvir; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial to Evaluate the Efficacy and Safety of a Combination Regimen of MK-5172 With/Without MK-8742 and/or Ribavirin (RBV) in Treatment-naive Subjects With Chronic Hepatitis C Genotype 2, 4, 5 and 6 Infection
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Dec 4, 2014
• Actual Study Completion Date: Dec 4, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GT2: Grazoprevir + Elbasvir + RBV (Arm A1) During Part A of the study, GT2 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks.	Drug: Grazoprevir; 100 mg every day (QD) orally; Other Names: MK-5172 ; Drug: Elbasvir; 50 mg QD orally; Other Names: MK-8742 ; Drug: Ribavirin; Administered twice daily (BID) orally at a total daily dose of 800 mg to 1400 mg based on participant's weight on Day 1; Other Names: Rebetol™
Experimental: GT2: Grazoprevir + RBV (Arm B1) During Part B of the study, GT2 participants will receive 100 mg grazoprevir + standard weight-based dosing of RBV for 12 weeks.	Drug: Grazoprevir; 100 mg every day (QD) orally; Other Names: MK-5172 ; Drug: Ribavirin; Administered twice daily (BID) orally at a total daily dose of 800 mg to 1400 mg based on participant's weight on Day 1; Other Names: Rebetol™
Experimental: GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2) During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir + standard weight-based dosing of RBV for 12 weeks.	Drug: Grazoprevir; 100 mg every day (QD) orally; Other Names: MK-5172 ; Drug: Elbasvir; 50 mg QD orally; Other Names: MK-8742 ; Drug: Ribavirin; Administered twice daily (BID) orally at a total daily dose of 800 mg to 1400 mg based on participant's weight on Day 1; Other Names: Rebetol™
Experimental: GT 4,5,6: Grazoprevir + Elbasvir (Arm B3) During Part B of the study, GT4/GT5/GT6 participants will receive 100 mg grazoprevir + 50 mg elbasvir for 12 weeks.	Drug: Grazoprevir; 100 mg every day (QD) orally; Other Names: MK-5172 ; Drug: Elbasvir; 50 mg QD orally; Other Names: MK-8742

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12) [12 weeks after end of all therapy (Study Week 24)]

   SVR12 was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) <25 IU/mL, either target detected but unquantifiable (TD[u]) or target not detected (TND), at 12 weeks after the end of all study therapy. The percentage of participants with SVR12 and accompanying 95% confidence intervals (CIs) were reported for each treatment arm in the Per-Protocol (PP) Population.

2. Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Drug-Related AEs, Drug-Related SAEs, or Discontinuation of Study Treatment Due to AE During the Treatment Period and First 14 Follow-up Days [Treatment period plus the first 14 days of follow-up (up to 14 weeks)]

   AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The investigator determined the relationship of the AE to the treatment as unrelated or possibly, probably, or definitely related.

Secondary Outcome Measures

1. Mean Time to First Achievement of Undetectable HCV RNA During Treatment [From TW1 until first achievement of undetectable HCV RNA (up to 12 weeks)]

   HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. Undetectable HCV RNA (or TND) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm in the Full Analysis Set (FAS).

2. Percentage of Participants Achieving Undetectable HCV RNA During Treatment By Timepoint [From TW 2 through TW 12 (up to 12 weeks)]

   HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. Undetectable HCV RNA (or TND) was defined as below the 9.3 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2, TW4, and TW12 for each treatment arm of the PP Population.

3. Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment By Timepoint [From TW 2 through TW 12 (up to 12 weeks)]

   HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. The Roche COBAS™ Taqman™ HCV Test (v.2.0) has a lower limit of quantification (LLoQ) of 25 IU/ml and a limit of detection of 9.3 IU/ml. The percentage of participants with HCV RNA levels <25 IU/ml (either TD[u] or TND) and accompanying 95% CIs were reported at TW2, TW4, and TW12 for each treatment arm of the PP Population.

4. Percentage of Participants Achieving SVR4 [4 weeks after end of all therapy (Study Week 16)]

   SVR4 was defined as HCV RNA <25 IU/mL, either TD(u) or TND, at 4 weeks after the end of all study therapy. The percentage of participants with SVR4 and accompanying 95% CIs were reported for each treatment arm of the PP Population.

5. Percentage of Participants Achieving SVR24 [24 weeks after end of all therapy (Study Week 36)]

   SVR24 was defined as HCV RNA <25 IU/mL, either TD(u) or TND, at 24 weeks after the end of all study therapy. The percentage of participants with SVR24 and accompanying 95% CIs were reported for each treatment arm of the PP Population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Parts A and B: -Body weight ≥50 kg (111 lbs) and ≤ 125 kg (275 lbs) -Has absence of cirrhosis -Agrees to use two acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations (for female participant who is of childbearing potential or male participant with female sexual partner who is of childbearing potential).

Part A only: -Has chronic HCV GT2 infection Part B only: -Has chronic HCV GT2, GT4, GT5, or GT6 infection

Exclusion Criteria:

Parts A and B:

-Is not treatment naïve (participant has had previous treatment with any interferon, RBV, approved or experimental direct acting antiviral(s), or other investigational therapies for HCV) -Is determined to be coinfected with hepatitis B virus (HBsAg positive) or HIV -Has evidence of, or is under evaluation for, hepatocellular carcinoma (HCC) -Has a clinical diagnosis of substance abuse including the following specified drugs within specified timeframes: Alcohol, intravenous drugs, inhalational, psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs (within 1 year of the screening visit), is receiving opiate agonist substitution therapy (within 1 year of screening visit), or excessive historic marijuana use -Has evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years -Female participant who is pregnant, lactating, expecting to conceive or donate eggs, or is of childbearing potential and unwilling to commit to two methods of birth control throughout treatment and after the completion of all treatment, or male participant who is planning to impregnate or provide sperm donation or has a female sexual partner of childbearing potential and is unwilling to commit to using a two methods of birth control throughout treatment and after the completion of all treatment -Has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis. -Has uncontrolled diabetes (documented HbA1c >8.5%)

Part A only:

-Has non GT2 HCV infection

Part B only:

-Has HCV infection with a genotype other than GT2, GT4, GT5 or GT6

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01932762
• Other Study ID Numbers: 5172-047; 2013-002169-21
• First Posted: Aug 30, 2013
• Last Update Posted: Feb 4, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Ribavirin; Grazoprevir

Study Results

Participant Flow

Pre-assignment Detail	98 participants were assigned to treatment at 28 sites worldwide and all enrolled participants received ≥1 dose of study therapy. 30 participants enrolled in Part A and 68 were enrolled and randomized in Part B of the study. Enrollment in Part C, an evaluation of a fixed-dose combination of grazoprevir and elbasvir, was never initiated.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of ribavirin (RBV) for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Period Title: Overall Study
STARTED	30	30	19	19
COMPLETED	24	28	19	18
NOT COMPLETED	6	2	0	1

Baseline Characteristics

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)	Total
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.	Total of all reporting groups
Overall Participants	30	30	19	19	98
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (13.6)	48.3 (14.6)	52.2 (9.3)	52.8 (12.3)	49.6 (13.0)
Sex: Female, Male (Count of Participants)
Female	11 36.7%	13 43.3%	11 57.9%	7 36.8%	42 42.9%
Male	19 63.3%	17 56.7%	8 42.1%	12 63.2%	56 57.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12)
Description	SVR12 was defined as Hepatitis C Virus ribonucleic acid (HCV RNA) <25 IU/mL, either target detected but unquantifiable (TD[u]) or target not detected (TND), at 12 weeks after the end of all study therapy. The percentage of participants with SVR12 and accompanying 95% confidence intervals (CIs) were reported for each treatment arm in the Per-Protocol (PP) Population.
Time Frame	12 weeks after end of all therapy (Study Week 24)

Outcome Measure Data

Analysis Population Description

All participants in the PP Population (all randomized participants receiving ≥1 dose of study therapy with no important protocol deviations) with available data.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	27	24	17	13
Number (95% Confidence Interval) [percentage of participants]	85.2 284%	75.0 250%	94.1 495.3%	76.9 404.7%

2. Primary Outcome

Title	Percentage of Participants With Adverse Events (AEs), Serious AEs (SAEs), Drug-Related AEs, Drug-Related SAEs, or Discontinuation of Study Treatment Due to AE During the Treatment Period and First 14 Follow-up Days
Description	AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. An SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The investigator determined the relationship of the AE to the treatment as unrelated or possibly, probably, or definitely related.
Time Frame	Treatment period plus the first 14 days of follow-up (up to 14 weeks)

Outcome Measure Data

Analysis Population Description

All-Subjects-As-Treated (ASAT) Population; all randomized participants who received ≥ 1 dose of study therapy. The percentage of participants with specific AEs and accompanying 95% CI were reported for each treatment arm.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	30	30	19	19
AEs	86.7 289%	86.7 289%	94.7 498.4%	78.9 415.3%
SAEs	3.3 11%	3.3 11%	0.0 0%	0.0 0%
Drug-related AE	63.3 211%	63.3 211%	57.9 304.7%	36.8 193.7%
Drug-related SAE	0.0 0%	3.3 11%	0.0 0%	0.0 0%
Discontinuation due to AE	0.0 0%	0.0 0%	0.0 0%	5.3 27.9%

3. Secondary Outcome

Title	Mean Time to First Achievement of Undetectable HCV RNA During Treatment
Description	HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. Undetectable HCV RNA (or TND) was defined as below the 9.3 IU/ml limit of detection. Kaplan Meier summary statistics were calculated for each treatment arm in the Full Analysis Set (FAS).
Time Frame	From TW1 until first achievement of undetectable HCV RNA (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

FAS; all randomized participants who received ≥1 dose of study therapy. Participants in the FAS not achieving TND were censored from the analysis.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	30	26	19	18
Mean (Standard Error) [days]	25.2 (2.8)	26.9 (3.0)	27.4 (4.5)	21.3 (1.7)

4. Secondary Outcome

Title	Percentage of Participants Achieving Undetectable HCV RNA During Treatment By Timepoint
Description	HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. Undetectable HCV RNA (or TND) was defined as below the 9.3 IU/ml limit of detection. The percentage of participants achieving undetectable HCV RNA and accompanying 95% CIs were reported at TW2, TW4, and TW12 for each treatment arm of the PP Population.
Time Frame	From TW 2 through TW 12 (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

All participants in the PP Population (all randomized participants receiving ≥1 dose of study therapy and with no important protocol deviations) with available data.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	28	24	17	15
Week 2 (n=28, 24, 16, 15)	42.9 143%	50.0 166.7%	50.0 263.2%	53.3 280.5%
Week 4 (n=28, 24, 17, 15)	85.7 285.7%	79.2 264%	88.2 464.2%	80.0 421.1%
Week 12 (n=28, 24, 17, 14)	96.4 321.3%	83.3 277.7%	100.0 526.3%	78.6 413.7%

5. Secondary Outcome

Title	Percentage of Participants Achieving HCV RNA <25 IU/mL During Treatment By Timepoint
Description	HCV-RNA levels in plasma were measured using the Roche COBAS™ Taqman™ HCV Test (v.2.0) on blood samples drawn from each participant during treatment at TWs 1, 2, 4, 8, and 12. The Roche COBAS™ Taqman™ HCV Test (v.2.0) has a lower limit of quantification (LLoQ) of 25 IU/ml and a limit of detection of 9.3 IU/ml. The percentage of participants with HCV RNA levels <25 IU/ml (either TD[u] or TND) and accompanying 95% CIs were reported at TW2, TW4, and TW12 for each treatment arm of the PP Population.
Time Frame	From TW 2 through TW 12 (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

All participants in the PP Population (all randomized participants receiving ≥1 dose of study therapy and with no important protocol deviations) with available data.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	28	24	17	15
Week 2 (n=28, 24, 16, 15)	96.4 321.3%	79.2 264%	87.5 460.5%	93.3 491.1%
Week 4 (n=28, 24, 17, 15)	100.0 333.3%	91.7 305.7%	100.0 526.3%	93.3 491.1%
Week 12 (n=28, 24, 17, 14)	96.4 321.3%	87.5 291.7%	100.0 526.3%	85.7 451.1%

6. Secondary Outcome

Title	Percentage of Participants Achieving SVR4
Description	SVR4 was defined as HCV RNA <25 IU/mL, either TD(u) or TND, at 4 weeks after the end of all study therapy. The percentage of participants with SVR4 and accompanying 95% CIs were reported for each treatment arm of the PP Population.
Time Frame	4 weeks after end of all therapy (Study Week 16)

Outcome Measure Data

Analysis Population Description

All participants in the PP Population (all randomized participants receiving ≥1 dose of study therapy and with no important protocol deviations) with available data.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	27	24	17	14
Number (95% Confidence Interval) [percentage of participants]	88.9 296.3%	83.3 277.7%	94.1 495.3%	78.6 413.7%

7. Secondary Outcome

Title	Percentage of Participants Achieving SVR24
Description	SVR24 was defined as HCV RNA <25 IU/mL, either TD(u) or TND, at 24 weeks after the end of all study therapy. The percentage of participants with SVR24 and accompanying 95% CIs were reported for each treatment arm of the PP Population.
Time Frame	24 weeks after end of all therapy (Study Week 36)

Outcome Measure Data

Analysis Population Description

All participants in the PP Population (all randomized participants receiving ≥1 dose of study therapy and with no important protocol deviations) with available data.

Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)	GT2: Grazoprevir + RBV (Arm B1)	GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)	GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.	During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
Measure Participants	26	24	17	13
Number (95% Confidence Interval) [percentage of participants]	84.6 282%	75.0 250%	94.1 495.3%	76.9 404.7%

Adverse Events

Time Frame	From TW1 through FW 24 (up to 36 weeks)
Adverse Event Reporting Description	AEs were reported for the ASAT Population (all randomized participants who received ≥1 dose of study therapy) for both the treatment and follow-up periods.
Arm/Group Title	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)		GT2: Grazoprevir + RBV (Arm B1)		GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)		GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
Arm/Group Description	During Part A of the study, GT2 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.		During Part B of the study, GT2 participants received 100 mg grazoprevir plus standard weight-based dosing of RBV for 12 weeks.		During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir plus standard weight-based dosing of RBV for 12 weeks.		During Part B of the study, GT4/GT5/GT6 participants received 100 mg grazoprevir plus 50 mg elbasvir for 12 weeks.
All Cause Mortality
	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)		GT2: Grazoprevir + RBV (Arm B1)		GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)		GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)		GT2: Grazoprevir + RBV (Arm B1)		GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)		GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		1/30 (3.3%)		0/19 (0%)		0/19 (0%)
Infections and infestations
Urinary tract infection	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	0/19 (0%)	0
Renal and urinary disorders
Renal failure acute	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	0/19 (0%)	0
Vascular disorders
Flushing	0/30 (0%)	0	1/30 (3.3%)	1	0/19 (0%)	0	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	GT2: Grazoprevir + Elbasvir + RBV (Arm A1)		GT2: Grazoprevir + RBV (Arm B1)		GT 4,5,6: Grazoprevir + Elbasvir + RBV (Arm B2)		GT 4,5,6: Grazoprevir + Elbasvir (Arm B3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/30 (86.7%)		25/30 (83.3%)		18/19 (94.7%)		15/19 (78.9%)
Blood and lymphatic system disorders
Anaemia	4/30 (13.3%)	5	2/30 (6.7%)	2	1/19 (5.3%)	1	0/19 (0%)	0
Cardiac disorders
Palpitations	1/30 (3.3%)	1	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	1/19 (5.3%)	1
Abdominal pain	1/30 (3.3%)	1	1/30 (3.3%)	1	2/19 (10.5%)	2	0/19 (0%)	0
Abdominal pain upper	2/30 (6.7%)	3	0/30 (0%)	0	0/19 (0%)	0	2/19 (10.5%)	2
Abdominal tenderness	0/30 (0%)	0	1/30 (3.3%)	1	0/19 (0%)	0	1/19 (5.3%)	1
Constipation	3/30 (10%)	3	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Diarrhoea	1/30 (3.3%)	1	1/30 (3.3%)	2	1/19 (5.3%)	1	4/19 (21.1%)	4
Dry mouth	2/30 (6.7%)	2	1/30 (3.3%)	1	3/19 (15.8%)	3	1/19 (5.3%)	1
Dyspepsia	2/30 (6.7%)	2	2/30 (6.7%)	2	1/19 (5.3%)	1	0/19 (0%)	0
Enteritis	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Faeces pale	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Gastrooesophageal reflux disease	0/30 (0%)	0	2/30 (6.7%)	2	1/19 (5.3%)	1	1/19 (5.3%)	1
Haemorrhoids	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	2/19 (10.5%)	2
Lip dry	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Mouth ulceration	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Nausea	5/30 (16.7%)	5	4/30 (13.3%)	6	2/19 (10.5%)	3	1/19 (5.3%)	1
Stomatitis	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	3
Vomiting	5/30 (16.7%)	6	2/30 (6.7%)	3	0/19 (0%)	0	1/19 (5.3%)	1
General disorders
Asthenia	5/30 (16.7%)	5	6/30 (20%)	6	3/19 (15.8%)	3	4/19 (21.1%)	4
Chest pain	1/30 (3.3%)	1	1/30 (3.3%)	1	1/19 (5.3%)	1	0/19 (0%)	0
Fatigue	12/30 (40%)	13	6/30 (20%)	7	5/19 (26.3%)	5	3/19 (15.8%)	3
Feeling cold	0/30 (0%)	0	1/30 (3.3%)	1	1/19 (5.3%)	1	0/19 (0%)	0
Influenza like illness	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Pyrexia	2/30 (6.7%)	2	1/30 (3.3%)	1	0/19 (0%)	0	2/19 (10.5%)	2
Thirst	0/30 (0%)	0	2/30 (6.7%)	2	0/19 (0%)	0	0/19 (0%)	0
Hepatobiliary disorders
Hepatomegaly	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Infections and infestations
Bronchitis	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Influenza	3/30 (10%)	3	1/30 (3.3%)	1	0/19 (0%)	0	0/19 (0%)	0
Laryngitis	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Nasopharyngitis	0/30 (0%)	0	2/30 (6.7%)	2	1/19 (5.3%)	1	0/19 (0%)	0
Oral herpes	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Rhinitis	0/30 (0%)	0	2/30 (6.7%)	2	0/19 (0%)	0	1/19 (5.3%)	1
Sinusitis	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Skin infection	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Urinary tract infection	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	1/19 (5.3%)	1
Viral infection	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	4/30 (13.3%)	7	4/30 (13.3%)	6	1/19 (5.3%)	1	0/19 (0%)	0
Foot fracture	0/30 (0%)	0	1/30 (3.3%)	1	0/19 (0%)	0	1/19 (5.3%)	1
Inflammation of wound	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Investigations
Alanine aminotransferase increased	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	2/19 (10.5%)	2
Aspartate aminotransferase increased	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Blood bilirubin increased	2/30 (6.7%)	2	0/30 (0%)	0	0/19 (0%)	0	0/19 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/30 (3.3%)	1	2/30 (6.7%)	2	1/19 (5.3%)	1	0/19 (0%)	0
Dyslipidaemia	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/30 (3.3%)	1	3/30 (10%)	4	1/19 (5.3%)	1	3/19 (15.8%)	9
Back pain	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	2/19 (10.5%)	3
Bone pain	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Flank pain	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Joint swelling	1/30 (3.3%)	1	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Muscle contracture	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Musculoskeletal pain	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Myalgia	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Neck pain	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	2/19 (10.5%)	2
Pain in extremity	0/30 (0%)	0	1/30 (3.3%)	1	1/19 (5.3%)	1	0/19 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Nervous system disorders
Disturbance in attention	1/30 (3.3%)	1	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Dizziness	7/30 (23.3%)	8	1/30 (3.3%)	2	0/19 (0%)	0	1/19 (5.3%)	2
Dysgeusia	2/30 (6.7%)	2	0/30 (0%)	0	0/19 (0%)	0	0/19 (0%)	0
Headache	6/30 (20%)	8	4/30 (13.3%)	5	6/19 (31.6%)	8	5/19 (26.3%)	20
Hypoaesthesia	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Lethargy	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Memory impairment	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Poor quality sleep	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Somnolence	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Psychiatric disorders
Depressed mood	2/30 (6.7%)	2	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Depression	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Insomnia	2/30 (6.7%)	3	1/30 (3.3%)	1	3/19 (15.8%)	3	2/19 (10.5%)	3
Irritability	3/30 (10%)	3	1/30 (3.3%)	1	1/19 (5.3%)	1	1/19 (5.3%)	1
Sleep disorder	0/30 (0%)	0	2/30 (6.7%)	2	0/19 (0%)	0	0/19 (0%)	0
Renal and urinary disorders
Dysuria	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Reproductive system and breast disorders
Genital tract inflammation	0/30 (0%)	0	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	5/30 (16.7%)	5	1/30 (3.3%)	1	4/19 (21.1%)	4	4/19 (21.1%)	5
Dyspnoea	4/30 (13.3%)	4	1/30 (3.3%)	1	1/19 (5.3%)	1	0/19 (0%)	0
Dyspnoea exertional	1/30 (3.3%)	1	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Oropharyngeal pain	1/30 (3.3%)	1	1/30 (3.3%)	2	0/19 (0%)	0	3/19 (15.8%)	3
Rhinorrhoea	1/30 (3.3%)	1	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Alopecia	3/30 (10%)	3	0/30 (0%)	0	0/19 (0%)	0	0/19 (0%)	0
Dry skin	1/30 (3.3%)	1	1/30 (3.3%)	1	1/19 (5.3%)	1	0/19 (0%)	0
Eczema	0/30 (0%)	0	1/30 (3.3%)	1	0/19 (0%)	0	1/19 (5.3%)	2
Pruritus	2/30 (6.7%)	3	1/30 (3.3%)	1	2/19 (10.5%)	3	1/19 (5.3%)	2
Rash	2/30 (6.7%)	2	2/30 (6.7%)	2	3/19 (15.8%)	5	0/19 (0%)	0
Vascular disorders
Hypertension	1/30 (3.3%)	1	0/30 (0%)	0	1/19 (5.3%)	1	0/19 (0%)	0
Hypotension	0/30 (0%)	0	0/30 (0%)	0	0/19 (0%)	0	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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. Sponsor review can be expedited to meet publication timelines.