A Study to Evaluate the Efficacy and Safety of Boceprevir Added to Standard of Care Therapy in Previously Treated Participants With Chronic Hepatitis C Genotype 1 and Cirrhosis (MK-3034-105)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01756079
• Collaborator: (none)
• Enrollment: 58
• Arm: 1
• Actual Duration (Months): 33.3

Study Details

Study Description

Brief Summary

This study is being done to find out if the addition of boceprevir to standard of care (SOC) treatment with peginterferon alfa-2b (PegIFN-2b) + ribavirin (RBV) is effective for participants with chronic hepatitis C (CHC) genotype 1 and cirrhosis who were not successfully treated by previous SOC. All participants will receive treatment with SOC alone for 4 weeks and then boceprevir will be added to the treatment regimen for 44 additional weeks of combined treatment.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: boceprevir; Biological: PegIFN-2b; Drug: RBV	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-centre Single-arm Study to Evaluate the Efficacy and Safety of BOCEPREVIR 44 Weeks in Addition to Standard of Care (SOC) in Previously Treatment Failure (Relapser, Non-responders, Both Partial and Null) Patients With Chronic Hepatitis C Genotype 1 (G1) and Cirrhosis (F4 Metavir). (MK-3034-105)
• Actual Study Start Date: Feb 6, 2013
• Actual Primary Completion Date: Nov 17, 2015
• Actual Study Completion Date: Nov 17, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: PegIFN-2b + RBV+ boceprevir Participants will receive PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks and then will receive 44 additional weeks of treatment with PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day).

Drug: boceprevir; Other Names: SCH 503034 ; Biological: PegIFN-2b; Other Names: Peginterferon alfa-2b PegIntron SCH 054031 ; Drug: RBV; Other Names: Ribavirin Rebetol

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Achieve Sustained Virological Response at Follow-up Week 24 (SVR24) [Week 72 (24 weeks after end of treatment)]

   Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using a polymerase chain reaction assay. SVR24 was defined as HCV RNA less than the Limit of Quantification (<25 International Units (IU)/mL) 24 weeks after the end of the Treatment Period.

2. Percentage of Participants With One or More Adverse Events [Up to 48 weeks (Lead-in and Treatment Periods)]

   Adverse events were monitored during the Lead-in and Treatment Periods

3. Percentage of Participants With an Adverse Event Leading to Discontinuation of Study Medication [Up to 48 weeks (Lead-in and Treatment Periods)]

   Adverse events were monitored during the Lead-in and Treatment Periods

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Weight between 40 kg and 125 kg

• Documented CHC genotype 1 infection

• Previous course of treatment with SOC (PegIFN-2a or PegIFN-2b + RBV) with a documented non-response

• Documented diagnosis of cirrhosis

• No evidence of hepatocellular carcinoma (HCC) by ultrasound

• Participant and partner of participant must agree to use 2 effective contraceptives as specified for at least 2 weeks prior to Day 1 of treatment and continue until at least 6 months after last dose of study drug (7 months for male participants)

Exclusion criteria:

• Co-infection with human immunodeficiency virus (HIV) or hepatitis B virus

• Use of any investigational drugs within 30 days prior to study enrollment

• Participation in any other clinical trial within 30 days of study enrollment or intention to participate in another clinical trial during this study

• Evidence of present or previous decompensated liver disease including, but not limited to, a history or presence of clinical ascites or hepatic encephalopathy. Only participants with large (F3) esophageal varices, as determined in an esophagogastroduodenoscopy (EGD) performed within the past 12 months according to international guidelines will be excluded.

• Clinically significant ocular examination findings

• Pre-existing significant psychiatric condition(s)

• Clinical diagnosis of active or recent substance abuse

• Evidence of active or suspected malignancy, or a history of malignancy, within the last 3 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin)

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: NCT01756079
• Other Study ID Numbers: 3034-105; 2012-002772-13
• First Posted: Dec 24, 2012
• Last Update Posted: Sep 5, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ribavirin; Peginterferon alfa-2b

Study Results

Participant Flow

Pre-assignment Detail	A total of 130 participants were screened. Sixty participants passed screening, but 2 of these participants were excluded before assignment because standard of care treatment was not received during the Lead-in Period.

Arm/Group Title	Overall Participants
Arm/Group Description	Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day). After completion of treatment, follow-up continued for an additional 24 weeks.
Period Title: Lead-in: Day 0 to Week 4
STARTED	58
COMPLETED	58
NOT COMPLETED	0
Period Title: Lead-in: Day 0 to Week 4
STARTED	58
Treated in Treatment Period	54
COMPLETED	23
NOT COMPLETED	35

Baseline Characteristics

Arm/Group Title	Overall Participants
Arm/Group Description	Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day). After completion of treatment, follow-up continued for an additional 24 weeks.
Overall Participants	58
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.3 (9.2)
Sex: Female, Male (Count of Participants)
Female	19 32.8%
Male	39 67.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Achieve Sustained Virological Response at Follow-up Week 24 (SVR24)
Description	Hepatitis C Virus (HCV) ribonucleic acid (RNA) was measured using a polymerase chain reaction assay. SVR24 was defined as HCV RNA less than the Limit of Quantification (<25 International Units (IU)/mL) 24 weeks after the end of the Treatment Period.
Time Frame	Week 72 (24 weeks after end of treatment)

Outcome Measure Data

Analysis Population Description

The Intent to Treat population included all participants who received at least 1 administration of boceprevir during the Treatment Period.

Arm/Group Title	Overall Participants
Arm/Group Description	Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day). After completion of treatment, follow-up continued for an additional 24 weeks.
Measure Participants	54
Number (95% Confidence Interval) [Percentage of participants]	35.2 60.7%

2. Primary Outcome

Title	Percentage of Participants With One or More Adverse Events
Description	Adverse events were monitored during the Lead-in and Treatment Periods
Time Frame	Up to 48 weeks (Lead-in and Treatment Periods)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set 2 included all participants who received boceprevir during the Treatment Period

Arm/Group Title	Overall Participants
Arm/Group Description	Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day).
Measure Participants	54
Number [Percentage of participants]	98.1 169.1%

3. Primary Outcome

Title	Percentage of Participants With an Adverse Event Leading to Discontinuation of Study Medication
Description	Adverse events were monitored during the Lead-in and Treatment Periods
Time Frame	Up to 48 weeks (Lead-in and Treatment Periods)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set 2 included all participants who received boceprevir during the Treatment Period

Arm/Group Title	Overall Participants
Arm/Group Description	Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day).
Measure Participants	54
Number [Percentage of participants]	9.3 16%

Adverse Events

Time Frame	Up to 72 weeks (including Lead-in, Treatment, and Follow-up Periods)
Adverse Event Reporting Description	Safety Analysis Set 1 included all participants who received PegIFN-2b + RBV during the Lead-in Period
Arm/Group Title	Overall Participants: Lead-in, Treatment and Follow-up
Arm/Group Description	Participants received PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) for 4 weeks during the Lead-in Period and then 44 additional weeks of treatment in the Treatment Period receiving PegIFN-2b (once weekly, 1.5 µg/kg subcutaneously) + RBV (capsules, orally, weight-based dose from 800-1400 mg/day divided into two daily doses) + boceprevir (capsules, orally, 800 mg three times per day). After completion of treatment, follow-up continued for an additional 24 weeks.
All Cause Mortality
	Overall Participants: Lead-in, Treatment and Follow-up
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Overall Participants: Lead-in, Treatment and Follow-up
	Affected / at Risk (%)	# Events
Total	10/58 (17.2%)
Blood and lymphatic system disorders
Anaemia	4/58 (6.9%)	5
Gastrointestinal disorders
Nausea	1/58 (1.7%)	1
Vomiting	2/58 (3.4%)	2
General disorders
Asthenia	1/58 (1.7%)	1
Chest pain	1/58 (1.7%)	1
Hyperpyrexia	1/58 (1.7%)	1
Pyrexia	2/58 (3.4%)	2
Infections and infestations
Parathyroid fever	1/58 (1.7%)	1
Pneumonia	2/58 (3.4%)	2
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/58 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma	3/58 (5.2%)	3
Nervous system disorders
Encephalopathy	1/58 (1.7%)	1
Headache	1/58 (1.7%)	1
Psychiatric disorders
Confusional state	1/58 (1.7%)	1
Renal and urinary disorders
Renal impairment	1/58 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/58 (1.7%)	1
Vascular disorders
Hypotension	1/58 (1.7%)	1
Peripheral artery stenosis	1/58 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Overall Participants: Lead-in, Treatment and Follow-up
	Affected / at Risk (%)	# Events
Total	56/58 (96.6%)
Blood and lymphatic system disorders
Anaemia	44/58 (75.9%)	82
Leukopenia	5/58 (8.6%)	5
Neutropenia	16/58 (27.6%)	22
Thrombocytopenia	7/58 (12.1%)	8
Endocrine disorders
Hypothyroidism	3/58 (5.2%)	3
Eye disorders
Lacrimation increased	3/58 (5.2%)	3
Gastrointestinal disorders
Nausea	12/58 (20.7%)	13
Vomiting	6/58 (10.3%)	10
Abdominal distension	3/58 (5.2%)	4
Constipation	3/58 (5.2%)	3
Diarrhoea	7/58 (12.1%)	7
Dry mouth	5/58 (8.6%)	5
Dyspepsia	7/58 (12.1%)	9
General disorders
Adverse drug reaction	11/58 (19%)	11
Asthenia	35/58 (60.3%)	42
Influenza like illness	5/58 (8.6%)	12
Pyrexia	15/58 (25.9%)	35
Fatigue	3/58 (5.2%)	3
Injury, poisoning and procedural complications
Accidental overdose	5/58 (8.6%)	5
Metabolism and nutrition disorders
Decreased appetite	12/58 (20.7%)	13
Musculoskeletal and connective tissue disorders
Arthralgia	5/58 (8.6%)	6
Myalgia	5/58 (8.6%)	5
Nervous system disorders
Headache	6/58 (10.3%)	8
Dysgeusia	14/58 (24.1%)	15
Syncope	3/58 (5.2%)	3
Psychiatric disorders
Insomnia	7/58 (12.1%)	7
Irritability	3/58 (5.2%)	3
Renal and urinary disorders
Nocturia	4/58 (6.9%)	4
Pollakiuria	3/58 (5.2%)	3
Respiratory, thoracic and mediastinal disorders
Cough	15/58 (25.9%)	15
Dyspnoea	7/58 (12.1%)	7
Skin and subcutaneous tissue disorders
Alopecia	4/58 (6.9%)	4
Dry skin	5/58 (8.6%)	6
Pruritus generalized	3/58 (5.2%)	3
Rash	3/58 (5.2%)	3
Vascular disorders
Hypotension	3/58 (5.2%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation.