Trial Outcomes & Findings for Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination in Treatment-Naïve Hepatitis C Virus Participants (MK-5172-067) (NCT NCT02251990)

NCT ID: NCT02251990

Last Updated: 2019-01-30

Results Overview

Blood was drawn from each participant to assess Hepatitis C Virus ribonucleic acid (HCV RNA) plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a lower limit of quantification (LLOQ) of 15 IU/mL. SVR12 was defined as HCV RNA below the lower limit of detection (\<LLOQ) at 12 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the primary efficacy analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

489 participants

Primary outcome timeframe

12 weeks after end of all therapy (Study Week 24)

Results posted on

2019-01-30

Participant Flow

For Subject Disposition, Period 1 covers Day 1 through Week 12 for both treatment groups. Period 2 covers Week 12 through Week 36 for the Immediate Treatment Group (ITG) and Week 12 through Week 28 for the Deferred Treatment Group (DTG). Period 3 covers Week 28 through Week 52 for the DTG; the ITG completed the study with Period 2.

A total of 489 participants were randomized to treatment, and 488 participants received ≥1 dose of study drug during the blinded period. One participant randomized to the ITG withdrew consent after randomization, but prior to receiving study drug.

Participant milestones

Participant milestones
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Participants received a grazoprevir/elbasvir fixed-dose combination (FDC) tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Period 1 (Double-blind [DB]) STARTED	366	123
Period 1 (Double-blind [DB]) Treated	365	123
Period 1 (Double-blind [DB]) COMPLETED	358	122
Period 1 (Double-blind [DB]) NOT COMPLETED	8	1
Period 2 (ITG Follow-up/DTG Open Label) STARTED	360	121
Period 2 (ITG Follow-up/DTG Open Label) COMPLETED	360	118
Period 2 (ITG Follow-up/DTG Open Label) NOT COMPLETED	0	3
Period 3 (DTG Follow-up) STARTED	0	121
Period 3 (DTG Follow-up) COMPLETED	0	121
Period 3 (DTG Follow-up) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir Participants received a grazoprevir/elbasvir fixed-dose combination (FDC) tablet once daily (q.d.) by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Period 1 (Double-blind [DB]) Adverse Event	1	1
Period 1 (Double-blind [DB]) Lack of Efficacy	5	0
Period 1 (Double-blind [DB]) Withdrawal by Subject	1	0
Period 1 (Double-blind [DB]) Not Treated	1	0
Period 2 (ITG Follow-up/DTG Open Label) Lack of Efficacy	0	1
Period 2 (ITG Follow-up/DTG Open Label) Adverse Event	0	2

Baseline Characteristics

Grazoprevir (MK-5172) and Elbasvir (MK-8742) Combination in Treatment-Naïve Hepatitis C Virus Participants (MK-5172-067)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 Participants Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir n=123 Participants Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.	Total n=488 Participants Total of all reporting groups
Age, Continuous	48.1 years STANDARD_DEVIATION 12.9 • n=5 Participants	48.6 years STANDARD_DEVIATION 12.9 • n=7 Participants	48.3 years STANDARD_DEVIATION 12.9 • n=5 Participants
Sex: Female, Male Female	205 Participants n=5 Participants	67 Participants n=7 Participants	272 Participants n=5 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	56 Participants n=7 Participants	216 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks after end of all therapy (Study Week 24)

Population: All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 Participants Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After the End of All Study Therapy (SVR12)	94.2 percentage of participants Interval 91.5 to 97.0	—

PRIMARY outcome

Timeframe: DB Treatment period plus first 14 follow-up days (up to 14 weeks)

Population: All randomized participants who received at least one dose of study treatment during the double-blind treatment period.

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. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.

Outcome measures

Outcome measures
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 Participants Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir n=123 Participants Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Percentage of Participants Experiencing at Least One Adverse Event (AE) During the DB Treatment Period and First 14 Follow-up Days	50.7 percentage of participants	51.2 percentage of participants

PRIMARY outcome

Timeframe: DB Treatment period (up to 12 weeks)

Population: All randomized participants who received at least one dose of study treatment during the double-blind treatment period.

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. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product, is also an AE. A participant could discontinue from treatment but continue to participate in the study as long as consent was not withdrawn. The primary safety analysis compared the safety data of the Immediate Treatment Group during the active treatment period to those of the Deferred Treatment Group during the placebo treatment period.

Outcome measures

Outcome measures
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 Participants Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir n=123 Participants Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Percentage of Participants That Discontinued From Study Therapy Due to AEs During the DB Treatment Period	0.3 percentage of participants	0.8 percentage of participants

SECONDARY outcome

Timeframe: 24 weeks after end of all therapy (Study Week 36)

Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR24 was defined as HCV RNA \<LLOQ at 24 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in the secondary efficacy analysis.

Outcome measures

Outcome measures
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 Participants Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After the End of All Study Therapy (SVR24)	94.0 percentage of participants Interval 91.5 to 96.4	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 weeks after end of all therapy (Study Week 16)

Population: All randomized participants in the Immediate Treatment Group who received at least one dose of study treatment. The Deferred Treatment Group was not included in this efficacy analysis.

Blood was drawn from each participant to assess HCV RNA plasma levels using the Roche COBAS® AmpliPrep/COBAS® Taqman HCV Test, v2.0, which had a LLOQ of 15 IU/mL. SVR4 was defined as HCV RNA \<LLOQ at 4 weeks after the end of all study therapy. As pre-specified in the protocol, the Deferred Treatment Group was not included in this efficacy analysis.

Outcome measures

Outcome measures
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 Participants Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36.	Deferred Treatment Group (DTG): Placebo > Grazoprevir/Elbasvir Participants received a placebo tablet q.d. by mouth for 12 weeks (placebo treatment period). After a 4-week Follow-Up period, participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Percentage of Participants Achieving Sustained Virologic Response 4 Weeks After the End of All Study Therapy (SVR4)	96.2 percentage of participants Interval 94.2 to 98.1	—

Adverse Events

Immediate Treatment Group (ITG): Grazoprevir/Elbasvir

Serious events: 9 serious events

Other events: 85 other events

Deaths: 0 deaths

Deferred Treatment Group (DTG): Placebo

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Deferred Treatment Group (DTG): Grazoprevir/Elbasvir

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Immediate Treatment Group (ITG): Grazoprevir/Elbasvir n=365 participants at risk Participants received a grazoprevir/elbasvir FDC tablet q.d. by mouth during a 12-week Active Treatment period (Week 1 to Week 12) and were followed-up for 24 weeks to Week 36	Deferred Treatment Group (DTG): Placebo n=123 participants at risk Participants received a placebo tablet q.d. by mouth for 12 weeks during the double-blind treatment period (Weeks 1 to 12). Participants were then followed-up for 4 weeks to Week 16.	Deferred Treatment Group (DTG): Grazoprevir/Elbasvir n=121 participants at risk Participants received open-label grazoprevir/elbasvir FDC during a 12-week Active Treatment period (Week 16 to Week 28). Participants were then followed-up for 24 weeks to Week 52.
Gastrointestinal disorders Diarrhoea	5.8% 21/365 • Number of events 22 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	6.5% 8/123 • Number of events 8 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	2.5% 3/121 • Number of events 3 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.
General disorders Fatigue	5.8% 21/365 • Number of events 21 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	6.5% 8/123 • Number of events 8 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	0.83% 1/121 • Number of events 1 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.
Infections and infestations Upper respiratory tract infection	7.1% 26/365 • Number of events 30 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	6.5% 8/123 • Number of events 9 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	8.3% 10/121 • Number of events 10 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.
Investigations Alanine aminotransferase increased	1.6% 6/365 • Number of events 6 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	5.7% 7/123 • Number of events 7 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	4.1% 5/121 • Number of events 6 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.
Investigations Aspartate aminotransferase increased	1.6% 6/365 • Number of events 6 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	5.7% 7/123 • Number of events 9 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	3.3% 4/121 • Number of events 4 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.
Nervous system disorders Headache	6.6% 24/365 • Number of events 24 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	4.9% 6/123 • Number of events 11 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.	5.0% 6/121 • Number of events 9 • Immediate Treatment Group = Up to Week 36; Deferred Treatment: Placebo Group = Up to Week 16; Deferred Treatment: Grazoprevir/Elbasvir Group = Week 16 to Week 52 All randomized participants who received ≥1 dose of study treatment and had any safety follow-up data. AEs were reported by the treatment that participants were receiving at the time of the event; AEs for Deferred Group reported separately for placebo and active treatment periods.

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. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER