A Study of Vaniprevir (MK-7009) in Participants With Chronic Hepatitis C Infection After Participation in Other Vaniprevir Studies (MK-7009-028)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00943761
• Collaborator: (none)
• Enrollment: 45
• Arms: 2
• Actual Duration (Months): 43.2

Study Details

Study Description

Brief Summary

This study will provide vaniprevir 600 mg or 300 mg twice daily in combination with pegylated interferon (peg-IFN) and ribavirin (RBV) to participants with chronic hepatitis C virus (HCV) infection who did not achieve viral eradication while participating in a prior vaniprevir clinical trial (MK-7009-004, NCT00518622; MK-7009-007, NCT00704405; MK-7009-009, NCT00704184; and MK-7009-029, NCT00954993).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Vaniprevir 600 mg b.i.d.; Drug: Vaniprevir 300 mg b.i.d.; Drug: Pegylated interferon; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Open Label Study of MK-7009 Administered Concomitantly With Pegylated Interferon Alfa-2a and Ribavirin to Patients With Chronic Hepatitis C Infection After Participation in Other MK-7009 Clinical Trials
• Actual Study Start Date: Oct 23, 2009
• Actual Primary Completion Date: May 29, 2013
• Actual Study Completion Date: May 29, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vaniprevir 300 mg b.i.d. + peg-IFN + RBV Participants received vaniprevir 300 mg twice daily (b.i.d.) in combination peg-IFN 180 mcg weekly and ribavirin (1000 or 1200 mg) administered as a divided dose twice daily.	Drug: Vaniprevir 300 mg b.i.d.; Oral capsules containing 150 mg vaniprevir, two in the morning and two in the evening, for 48 weeks; Drug: Pegylated interferon; Prefilled syringe containing 180 µg/0.5 mL peg-IFN, for weekly subcutaneous injection, for 48 weeks; Other Names: PEGASYS™ ; Drug: Ribavirin; Oral tablets containing 200 mg RBV, 5 or 6 tablets, dosage based on the participant's weight (<75 kg or ≥75 kg, respectively), for 48 weeks; Other Names: COPEGUS™
Experimental: Vaniprevir 600 mg b.i.d. + peg-IFN + RBV Participants received vaniprevir 600 mg b.i.d. in combination peg-IFN 180 mcg weekly and ribavirin (1000 or 1200 mg) administered as a divided dose twice daily.	Drug: Vaniprevir 600 mg b.i.d.; Oral capsules containing 150 mg vaniprevir, four in the morning and four in the evening, for 48 weeks; Drug: Pegylated interferon; Prefilled syringe containing 180 µg/0.5 mL peg-IFN, for weekly subcutaneous injection, for 48 weeks; Other Names: PEGASYS™ ; Drug: Ribavirin; Oral tablets containing 200 mg RBV, 5 or 6 tablets, dosage based on the participant's weight (<75 kg or ≥75 kg, respectively), for 48 weeks; Other Names: COPEGUS™

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced an Adverse Event [up to 72 weeks]

   An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.

2. Number of Participants Who Experienced a Serious Adverse Event [up to 72 weeks]

   Serious adverse event is defined as any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, was a congenital anomaly or birth defect, was a cancer, or was an overdose.

3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event [48 weeks]

   An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.

4. Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After the End of Treatment (SVR24) [72 weeks]

   SVR24 is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) 24 weeks after the end of vaniprevir study therapy. HCV RNA plasma levels were assessed using the Roche COBAS Taqman assay (or equivalent) with the limit of quantification (LoQ) of at least 25 IU/mL and the limit of detection (LoD) of at least 10 IU/mL.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Participant has participated in a prior vaniprevir clinical trial

• Participant agrees to use acceptable birth control method during treatment

Exclusion criteria:

• More than one year has passed since the participant was determined to be eligible for enrollment in protocol 028

• Participant discontinued vaniprevir and/or peg-IFN and/or RBV in the prior study due to a safety or tolerability issue

• Participant received any investigational therapy for HCV after participating in the prior study

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: NCT00943761
• Other Study ID Numbers: 7009-028; 2009_615; 2009-013053-15
• First Posted: Jul 22, 2009
• Last Update Posted: Feb 8, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Merck Sharp & Dohme LLC: hepatitis C
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Interferons; Ribavirin

Study Results

Participant Flow

Arm/Group Title	Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV	Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination pegylated interferon (peg-IFN) 180 mcg weekly and ribavirin (RBV) 1000 or 1200 mg administered as a divided dose twice daily.	Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and ribavirin 1000 or 1200 mg administered as a divided dose twice daily.
Period Title: Overall Study
STARTED	21	24
COMPLETED	17	23
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV	Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV	Total
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.	Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and ribavirin 1000 or 1200 mg administered as a divided dose twice daily.	Total of all reporting groups
Overall Participants	21	24	45
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.5 (7.4)	48.1 (8.4)	50.2 (8.1)
Sex: Female, Male (Count of Participants)
Female	7 33.3%	4 16.7%	11 24.4%
Male	14 66.7%	20 83.3%	34 75.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced an Adverse Event
Description	An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time Frame	up to 72 weeks

Outcome Measure Data

Analysis Population Description

All participants as treated population consists of all participants who received at least one dose of study treatment.

Arm/Group Title	Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV	Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.	Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and ribavirin 1000 or 1200 mg administered as a divided dose twice daily.
Measure Participants	21	24
Number [Participants]	21 100%	23 95.8%

2. Primary Outcome

Title	Number of Participants Who Experienced a Serious Adverse Event
Description	Serious adverse event is defined as any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, was a congenital anomaly or birth defect, was a cancer, or was an overdose.
Time Frame	up to 72 weeks

Outcome Measure Data

Analysis Population Description

All participants as treated population consists of all participants who received at least one dose of study treatment.

Arm/Group Title	Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV	Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.	Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and ribavirin 1000 or 1200 mg administered as a divided dose twice daily.
Measure Participants	21	24
Number [Participants]	4 19%	1 4.2%

3. Primary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
Description	An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

All participants as treated population consists of all participants who received at least one dose of study treatment.

Arm/Group Title	Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV	Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.	Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and ribavirin 1000 or 1200 mg administered as a divided dose twice daily.
Measure Participants	21	24
Number [Participants]	2 9.5%	1 4.2%

4. Primary Outcome

Title	Percentage of Participants Who Achieved Sustained Viral Response 24 Weeks After the End of Treatment (SVR24)
Description	SVR24 is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) 24 weeks after the end of vaniprevir study therapy. HCV RNA plasma levels were assessed using the Roche COBAS Taqman assay (or equivalent) with the limit of quantification (LoQ) of at least 25 IU/mL and the limit of detection (LoD) of at least 10 IU/mL.
Time Frame	72 weeks

Outcome Measure Data

Analysis Population Description

Population includes only a subset of participants previously treated with placebo + peg-IFN + RBV in a vaniprevir study and excludes participants for failure to receive >=1 dose of study drug, lack of any post-allocation endpoint data subsequent to >=1 dose of study drug, lack of baseline data, or missing data due to discontinuation from the study

Arm/Group Title	Vaniprevir 300 mg b.i.d. + Peg-IFN + RBV	Vaniprevir 600 mg b.i.d. + Peg-IFN + RBV
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.	Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and ribavirin 1000 or 1200 mg administered as a divided dose twice daily.
Measure Participants	18	17
Number (95% Confidence Interval) [Percentage of participants]	66.7 317.6%	70.6 294.2%

Adverse Events

Time Frame	up to 72 weeks
Arm/Group Title	Vaniprevir 300 mg Bid + Peg-IFN + RBV		Vaniprevir 600 mg Bid + Peg-IFN + RBV
Arm/Group Description	Participants received vaniprevir 300 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.		Participants received vaniprevir 600 mg twice daily in combination peg-IFN 180 mcg weekly and RBV 1000 or 1200 mg administered as a divided dose twice daily.
All Cause Mortality
	Vaniprevir 300 mg Bid + Peg-IFN + RBV		Vaniprevir 600 mg Bid + Peg-IFN + RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vaniprevir 300 mg Bid + Peg-IFN + RBV		Vaniprevir 600 mg Bid + Peg-IFN + RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/21 (19%)		1/24 (4.2%)
Blood and lymphatic system disorders
Anaemia	1/21 (4.8%)	1	0/24 (0%)	0
Gastrointestinal disorders
Constipation	1/21 (4.8%)	1	0/24 (0%)	0
Diarrhoea	1/21 (4.8%)	1	0/24 (0%)	0
Investigations
Alanine aminotransferase increased	1/21 (4.8%)	1	0/24 (0%)	0
Aspartate aminotransferase increased	1/21 (4.8%)	1	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/21 (0%)	0	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	Vaniprevir 300 mg Bid + Peg-IFN + RBV		Vaniprevir 600 mg Bid + Peg-IFN + RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		23/24 (95.8%)
Blood and lymphatic system disorders
Anaemia	5/21 (23.8%)	5	0/24 (0%)	0
Neutropenia	2/21 (9.5%)	3	2/24 (8.3%)	3
Gastrointestinal disorders
Abdominal distension	0/21 (0%)	0	2/24 (8.3%)	2
Abdominal pain	2/21 (9.5%)	2	3/24 (12.5%)	3
Abdominal pain upper	2/21 (9.5%)	2	2/24 (8.3%)	2
Constipation	2/21 (9.5%)	3	3/24 (12.5%)	3
Diarrhoea	5/21 (23.8%)	5	9/24 (37.5%)	14
Dyspepsia	1/21 (4.8%)	1	2/24 (8.3%)	2
Flatulence	0/21 (0%)	0	2/24 (8.3%)	2
Gastrooesophageal reflux disease	0/21 (0%)	0	3/24 (12.5%)	3
Haemorrhoids	0/21 (0%)	0	3/24 (12.5%)	3
Mouth ulceration	1/21 (4.8%)	1	3/24 (12.5%)	3
Nausea	8/21 (38.1%)	8	14/24 (58.3%)	17
Vomiting	3/21 (14.3%)	4	2/24 (8.3%)	4
General disorders
Asthenia	4/21 (19%)	4	6/24 (25%)	6
Fatigue	7/21 (33.3%)	7	5/24 (20.8%)	5
Influenza like illness	3/21 (14.3%)	4	4/24 (16.7%)	4
Irritability	2/21 (9.5%)	2	3/24 (12.5%)	3
Pyrexia	5/21 (23.8%)	6	3/24 (12.5%)	3
Infections and infestations
Nasopharyngitis	2/21 (9.5%)	2	3/24 (12.5%)	4
Urinary tract infection	3/21 (14.3%)	4	0/24 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	0/21 (0%)	0	2/24 (8.3%)	7
Investigations
Alanine aminotransferase increased	0/21 (0%)	0	2/24 (8.3%)	3
Aspartate aminotransferase increased	0/21 (0%)	0	2/24 (8.3%)	3
Weight decreased	2/21 (9.5%)	2	0/24 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	2/21 (9.5%)	3	5/24 (20.8%)	5
Hypokalaemia	2/21 (9.5%)	2	0/24 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	4/21 (19%)	5	2/24 (8.3%)	3
Back pain	1/21 (4.8%)	1	4/24 (16.7%)	5
Muscle spasms	3/21 (14.3%)	3	1/24 (4.2%)	1
Myalgia	3/21 (14.3%)	3	3/24 (12.5%)	3
Nervous system disorders
Dizziness	2/21 (9.5%)	4	3/24 (12.5%)	4
Headache	7/21 (33.3%)	7	9/24 (37.5%)	17
Sciatica	2/21 (9.5%)	2	0/24 (0%)	0
Tremor	2/21 (9.5%)	2	0/24 (0%)	0
Psychiatric disorders
Insomnia	3/21 (14.3%)	3	5/24 (20.8%)	5
Sleep disorder	3/21 (14.3%)	4	5/24 (20.8%)	5
Respiratory, thoracic and mediastinal disorders
Cough	2/21 (9.5%)	2	7/24 (29.2%)	7
Dyspnoea	1/21 (4.8%)	1	2/24 (8.3%)	2
Oropharyngeal pain	2/21 (9.5%)	2	3/24 (12.5%)	3
Productive cough	0/21 (0%)	0	2/24 (8.3%)	2
Skin and subcutaneous tissue disorders
Dermatitis	1/21 (4.8%)	1	2/24 (8.3%)	2
Dry skin	0/21 (0%)	0	2/24 (8.3%)	2
Eczema	2/21 (9.5%)	2	3/24 (12.5%)	3
Erythema	1/21 (4.8%)	1	3/24 (12.5%)	3
Pruritus	5/21 (23.8%)	5	6/24 (25%)	10
Rash	3/21 (14.3%)	3	1/24 (4.2%)	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 study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.