Trial Outcomes & Findings for Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Are Non-responders to Previous Treatment (MK-7009-045) (NCT NCT01405560)

NCT ID: NCT01405560

Last Updated: 2018-10-18

Results Overview

SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 42 participants
• Primary outcome timeframe: 24 weeks after 24 weeks of study therapy (up to 48 weeks)
• Results posted on: 2018-10-18

Participant Flow

Japanese patients 20-70 years old (inclusive) with chronic, compensated, genotype 1 Hepatitis C (HCV) infection and HCV ribonucleic acid (RNA) levels ≥5.0 log IU/mL peripheral blood at screening, who had failed to respond to prior interferon treatment, were recruited from 10 sites in Japan.

42 participants were randomized to receive 24 weeks of vaniprevir in combination with 24 weeks of peg-IFN α-2b (peg-IFN) and ribavirin (RBV).

Participant milestones

Measure	Vaniprevir 24 Week Arm Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Overall Study STARTED	42
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Vaniprevir 24 Week Arm Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Overall Study Physician Decision	1

Baseline Characteristics

Vaniprevir Plus PegIntron®/Ribavirin in Japanese Participants With Chronic Hepatitis C Who Are Non-responders to Previous Treatment (MK-7009-045)

Baseline characteristics by cohort

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Age, Continuous	57.4 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks after 24 weeks of study therapy (up to 48 weeks)

Population: Full Analysis Set (FAS) population; all randomized participants who received at least one dose of study treatment.

SVR24 was defined as having an undetectable HCV RNA level 24 weeks after completion of all study therapy. The percentage of participants achieving SVR24 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants Achieving Sustained Virologic Response (SVR)24	61.9 percentage of participants Interval 45.6 to 76.4

PRIMARY outcome

Timeframe: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)

Population: All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE. For this study, safety parameters or AEs of special interest that were identified a priori included serious rash, anemia (anemia plus haemoglobin decreased), neutropenia (neutropenia plus neutrophil count decreased), bilirubin increased and gastrointestinal adverse experiences (vomiting, nausea, and diarrhea). The percentage of participants with ≥1 specific AEs were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study With ≥1 specific AEs	78.6 percentage of participants Interval 63.2 to 89.7
Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study neutropenia	40.5 percentage of participants Interval 25.6 to 56.7
Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study anaemia	40.5 percentage of participants Interval 25.6 to 56.7
Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study bilirubin increased	7.1 percentage of participants Interval 1.5 to 19.5
Percentage of Participants With One or More Specific Adverse Events (AEs) of Special Interest During the Study GI AEs	52.4 percentage of participants Interval 36.4 to 68.0

PRIMARY outcome

Timeframe: From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)

Population: All Participants Treated (APaT) Population; all participants receiving at least one dose of study treatment

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also an AE.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants Who Discontinued Study Drug Due to an AE	2.4 percentage of participants

SECONDARY outcome

Timeframe: 12 weeks after 24 weeks of study therapy (up to 36 weeks)

Population: FAS population; all randomized participants who received at least one dose of study treatment.

SVR12 was defined as having an undetectable HCV RNA level 12 weeks after completion of all study therapy. The percentage of participants achieving SVR12 were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants Achieving SVR12	61.9 percentage of participants Interval 45.6 to 76.4

SECONDARY outcome

Timeframe: At Week 4

Population: FAS population; all randomized participants who received at least one dose of study treatment.

RVR was defined as having an undetectable HCV RNA level at Week 4. The percentage of participants achieving RVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants Achieving Rapid Virologic Response (RVR)	57.1 percentage of participants Interval 41.0 to 72.3

SECONDARY outcome

Timeframe: At Week 12

Population: FAS population; all randomized participants who received at least one dose of study treatment.

cEVR was defined as having an undetectable HCV RNA level at Week 12. The percentage of participants achieving cEVR were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants Achieving Complete Early Virologic Response (cEVR)	95.2 percentage of participants Interval 83.8 to 99.4

SECONDARY outcome

Timeframe: At Week 24

Population: FAS population; all randomized participants who received at least one dose of study treatment.

Participants were assessed for undetectable HCV RNA levels at the end of all study therapy. The percentage of participants with undetectable HCV RNA levels at EOT were reported along with corresponding 95% Clopper-Pearson exact confidence intervals for each treatment regimen.

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Percentage of Participants Achieving Undetectable HCV Ribonucleic Acid (RNA) at the End of Treatment (EOT)	95.2 percentage of participants Interval 83.8 to 99.4

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 4, Week 8, Week 12, Week 24

Population: FAS population; all randomized participants who received at least one dose of study treatment.

HCV RNA levels were assessed at baseline (BL) and during treatment weeks 2, 4, 8, 12, and 24 using the Roche TaqMan HCV assay, and transformed to Log 10 values. HCV RNA values below the limit of reliable quantification (LoQ) or the limit of detection (LoD) at any time point were handled as follows (imputations done for computational purposes): values below the LoQ but above the LoD were imputed with the LoQ minus 0.1; values below the LoD were imputed with the value of 0 Log IU/mL. HCV RNA levels below the LoD were considered "undetectable".

Outcome measures

Measure	Vaniprevir 24 Week Arm n=42 Participants Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Mean Change From Baseline in HCV RNA (Log 10) Change From BL at Week 2 (n=42)	-5.5 Log IU/ml Standard Deviation 0.6
Mean Change From Baseline in HCV RNA (Log 10) Change From BL at Week 4 (n=42)	-6.1 Log IU/ml Standard Deviation 0.7
Mean Change From Baseline in HCV RNA (Log 10) Change From BL at Week 8 (n=42)	-6.5 Log IU/ml Standard Deviation 0.7
Mean Change From Baseline in HCV RNA (Log 10) Change From BL at Week 12 (n=41)	-6.5 Log IU/ml Standard Deviation 1.0
Mean Change From Baseline in HCV RNA (Log 10) Change From BL at Week 24 (n=39)	-6.6 Log IU/ml Standard Deviation 0.6

Adverse Events

Vaniprevir 24 Week Arm

Serious events: 3 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vaniprevir 24 Week Arm n=42 participants at risk Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Infections and infestations Pneumonia bacterial	2.4% 1/42 • Number of events 1 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Injury, poisoning and procedural complications Cervical vertebral fracture	2.4% 1/42 • Number of events 1 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Nervous system disorders Loss of consciousness	2.4% 1/42 • Number of events 1 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)

Other adverse events

Measure	Vaniprevir 24 Week Arm n=42 participants at risk Participants receive 24 weeks of vaniprevir (300 mg twice daily) with concomitant peg-IFN and RBV treatment
Skin and subcutaneous tissue disorders Alopecia	31.0% 13/42 • Number of events 13 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Skin and subcutaneous tissue disorders Dry skin	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Skin and subcutaneous tissue disorders Pruritus	33.3% 14/42 • Number of events 14 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Skin and subcutaneous tissue disorders Rash	23.8% 10/42 • Number of events 12 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Blood and lymphatic system disorders Anaemia	28.6% 12/42 • Number of events 16 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Blood and lymphatic system disorders Neutropenia	9.5% 4/42 • Number of events 6 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Abdominal discomfort	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Abdominal pain upper	21.4% 9/42 • Number of events 10 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Constipation	16.7% 7/42 • Number of events 8 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Diarrhoea	16.7% 7/42 • Number of events 8 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Dry mouth	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Dyspepsia	14.3% 6/42 • Number of events 6 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Nausea	33.3% 14/42 • Number of events 15 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Stomatitis	14.3% 6/42 • Number of events 6 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Gastrointestinal disorders Vomiting	16.7% 7/42 • Number of events 8 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
General disorders Fatigue	14.3% 6/42 • Number of events 6 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
General disorders Influenza like illness	11.9% 5/42 • Number of events 5 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
General disorders Injection site erythema	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
General disorders Injection site reaction	28.6% 12/42 • Number of events 12 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
General disorders Malaise	28.6% 12/42 • Number of events 12 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
General disorders Pyrexia	59.5% 25/42 • Number of events 31 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Infections and infestations Nasopharyngitis	23.8% 10/42 • Number of events 12 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Alanine aminotransferase increased	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Bilirubin conjugated increased	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Blood bilirubin increased	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Blood uric acid increased	7.1% 3/42 • Number of events 4 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Haemoglobin decreased	11.9% 5/42 • Number of events 5 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Neutrophil count decreased	31.0% 13/42 • Number of events 14 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations Platelet count decreased	33.3% 14/42 • Number of events 14 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Investigations White blood cell count decreased	16.7% 7/42 • Number of events 7 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Metabolism and nutrition disorders Decreased appetite	9.5% 4/42 • Number of events 4 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Musculoskeletal and connective tissue disorders Myalgia	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Nervous system disorders Dysgeusia	23.8% 10/42 • Number of events 10 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Nervous system disorders Headache	28.6% 12/42 • Number of events 13 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Psychiatric disorders Insomnia	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Respiratory, thoracic and mediastinal disorders Cough	7.1% 3/42 • Number of events 3 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.9% 5/42 • Number of events 5 • From Day 1 (post-dose) through completion of Week 24 Follow-up (up to 48 weeks)

Additional Information

Vice President, Late Stage Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

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 study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
• Publication restrictions are in place

Restriction type: OTHER