LeeG3: Triple-Therapy in Patients With HCV Genotype 3 Who Previously Failed Treatment

• Sponsor: University of Calgary (Other)
• Overall Status: Completed
• CT.gov ID: NCT01585584
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 38
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to test the potential antiviral efficacy of triple-combination therapy with Peginterferon α-2b + ribavirin + boceprevir (PRB) in patients with HCV genotype 3 who previously failed Peginterferon α + ribavirin (non-responders or relapsers).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Boceprevir	Phase 3

Detailed Description

1. Obtain preliminary information on the association between important baseline and on-treatment factors and SVR in this patient population. Variables to be examined may include gender, age, advanced fibrosis or cirrhosis (F3 or F4 estimated by Fibroscan), baseline viral load, RVR, wk 8 viral load, end-of-treatment viral response.

2. Evaluate adverse events. iii) Evaluate viral resistance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Triple-Therapy With PegInterferon α-2b + Ribavirin + Boceprevir in Patients With HCV Genotype 3 Who Previously Failed Treatment With PegInterferon α + Ribavirin
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Boceprevir

Drug: Boceprevir; All patients will receive a 4-week lead-in with Peginterferon and Ribavirin therapy, followed by 24 weeks of Pegetron 1.5microg/kg + weight-based ribavirin + boceprevir 800mg tid. HCV RNA (Cobas TaqMan) will be measured at baseline and at treatment weeks 4, 6,8,12,16,20,24 and 28, and post-treatment weeks 12 and 24 (to obtain SVR-12 and SVR-24 results).; Other Names: VICTRELIS™ boceprevir capsules, 200 mg Hepatitis C Virus (HCV) Protease Inhibitor

Outcome Measures

Primary Outcome Measures

1. Sustained Virologic Response (SVR) at 24 Weeks Post Treatment [24 weeks after treatment]

   Sustained Virologic Response (SVR) is evaluated 24 weeks after end of treatment and defined as undetectable plasma HCV-RNA at follow up week 24. HCV RNA is measured using Cobas TaqMan.Of the 6 subjects who completed the treatment, 3 obtained SVR at 24 weeks post treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects will be eligible for the study if they meet the following inclusion criteria:

1. 18 years of age or older

2. Infected with HCV genotype 3 (mixed genotypes are NOT permitted)

3. Have received at least 12 weeks of previous treatment with peginterferon-α + ribavirin

4. Detectable serum HCV-RNA

5. No significant co-morbid conditions

6. Liver biopsy is not necessary

7. Cirrhotic patients will be eligible to participate if Child-Pugh class A (maximum 15% of subjects)

Exclusion Criteria:

• Subjects will be excluded from participation in this study if the following conditions are present:

1. Significant comorbidities: uncontrolled psychiatric conditions including severe depression, cardiovascular, respiratory, renal or metabolic conditions, active carcinoma.

2. Active substance abuse within the past 12 months

3. Co-infection with hepatitis B or HIV

4. Decompensated cirrhosis (Child-Pugh class B or C)

5. Significant cytopenia - any of the following: platelets <80 x 109/L, neutropenia <1.2 x 103/L, Hb <120 g/l for men or 110 g/l for women

6. Lack of informed consent

7. Previous null-responders (<2 log10 decrease at week 12 with previous PR therapy)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Calgary Liver Unit	Calgary	Alberta	Canada	T2N 4Z6

Sponsors and Collaborators

• University of Calgary
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Samuel Lee, MD, University of Calgary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sam Lee, Hepatologist, University of Calgary
• ClinicalTrials.gov Identifier: NCT01585584
• Other Study ID Numbers: MISP #39897; 24411
• First Posted: Apr 26, 2012
• Last Update Posted: Sep 21, 2015
• Last Verified: Aug 1, 2015

• Keywords provided by Sam Lee, Hepatologist, University of Calgary: Boceprevir; Hepatitis C Genotype 3
• Additional relevant MeSH terms: Hepatitis C; Hepatitis; Protease Inhibitors

Study Results

Participant Flow

Recruitment Details	It was hoped that 21 patients with chronic HCV genotype 3 who had failed to achieve an SVR with a standard course of treatment with Peginterferon α + ribavirin (PR) would be selected from the University of Calgary Liver Unit (UCLU) database. 11 patients were able to be enrolled in the study.The last patient completed the study in December 2014.
Pre-assignment Detail	Of the 11 patients who were enrolled in the study, 1 patient was a screen failure.

Arm/Group Title	Victrelis Triple
Arm/Group Description	All patients will receive a 4-week lead-in with peginterferon and ribavirin therapy, followed by 24 weeks of Pegetron 1.5mg/kg + weight-based ribavirin + boceprevir 800mg tid (Victrelis Triple)
Period Title: Overall Study
STARTED	10
COMPLETED	6
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Victrelis Triple
Arm/Group Description	All patients will receive a 4-week lead-in with peginterferon and ribavirin therapy, followed by 24 weeks of Pegetron 1.5mg/kg + weight-based ribavirin + boceprevir 800mg tid (Victrelis Triple)
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.3 (6.945)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
Region of Enrollment (participants) [Number]
Canada	10 100%

Outcome Measures

1. Primary Outcome

Title	Sustained Virologic Response (SVR) at 24 Weeks Post Treatment
Description	Sustained Virologic Response (SVR) is evaluated 24 weeks after end of treatment and defined as undetectable plasma HCV-RNA at follow up week 24. HCV RNA is measured using Cobas TaqMan.Of the 6 subjects who completed the treatment, 3 obtained SVR at 24 weeks post treatment.
Time Frame	24 weeks after treatment

Outcome Measure Data

Analysis Population Description

Patients who completed full course of treatment

Arm/Group Title	Victrelis Triple
Arm/Group Description	All patients will receive a 4-week lead-in with peginterferon and ribavirin therapy, followed by 24 weeks of Pegetron 1.5mg/kg + weight-based ribavirin + boceprevir 800mg tid (Victrelis Triple)
Measure Participants	6
Subjects who completed treatment	6 60%
Subjects who obtained SVR 24	3 30%

Adverse Events

Time Frame	52 weeks
Arm/Group Title	Victrelis Triple
Arm/Group Description	All patients will receive a 4-week lead-in with peginterferon and ribavirin therapy, followed by 24 weeks of Pegetron 1.5mg/kg + weight-based ribavirin + boceprevir 800mg tid (Victrelis Triple)
All Cause Mortality
	Victrelis Triple
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Victrelis Triple
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Infections and infestations
Emergency room visit due to suspected celulitis	1/10 (10%)	1
Reproductive system and breast disorders
Pregnancy in spouse	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Victrelis Triple
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	9/10 (90%)
Anisocytosis	1/10 (10%)
Delayed healing	3/10 (30%)
Increased LDL	1/10 (10%)
Hypercholesterolemia	2/10 (20%)
Hypertriglyceridemia	5/10 (50%)
Hypoalbuminema	4/10 (40%)
Hypochloremia	3/10 (30%)
Hypochromia	1/10 (10%)
Hyponatremia	1/10 (10%)
Increased INR	3/10 (30%)
Increased leukocytes	1/10 (10%)
Increased neutrophils	1/10 (10%)
Leukopenia	8/10 (80%)
Low HDL	1/10 (10%)
Lymphopenia	3/10 (30%)
Neutropenia	8/10 (80%)
Nose bleed	3/10 (30%)
Polychromasia	2/10 (20%)
Thrombocytopenia	8/10 (80%)
Low LDL	1/10 (10%)
Cardiac disorders
Orthostatic hypotension	2/10 (20%)
Transient heart rate increase	1/10 (10%)
Ear and labyrinth disorders
Dizziness	5/10 (50%)
Pulsatile tinnitus	2/10 (20%)
Endocrine disorders
Hypothyroidism	2/10 (20%)
Eye disorders
Blurred vision	3/10 (30%)
Irritated eyes	4/10 (40%)
Gastrointestinal disorders
Constipation	1/10 (10%)
Diarrhea	4/10 (40%)
Dysgeusia	8/10 (80%)
Dysphagia	1/10 (10%)
Nausea	5/10 (50%)
Tongue discolouration	1/10 (10%)
Indigestion	5/10 (50%)
Vomiting	2/10 (20%)
General disorders
Abdominal pain	3/10 (30%)
Chills	8/10 (80%)
Dry mouth	6/10 (60%)
Dry nose	1/10 (10%)
Fatigue	8/10 (80%)
Fever	7/10 (70%)
Headache	7/10 (70%)
Hyperactivity	1/10 (10%)
Insomnia	10/10 (100%)
Sinus congestion	3/10 (30%)
Peripheral edema	1/10 (10%)
Weight loss	5/10 (50%)
Immune system disorders
Worsening of psoriasis	2/10 (20%)
Infections and infestations
Cellulitis	1/10 (10%)
Metabolism and nutrition disorders
Anorexia	6/10 (60%)
Musculoskeletal and connective tissue disorders
Chest pain	2/10 (20%)
Joint pain	6/10 (60%)
Muscle pain	9/10 (90%)
Weakness	2/10 (20%)
Nervous system disorders
Numbness/tingling	2/10 (20%)
Resltess legs	1/10 (10%)
Psychiatric disorders
Anxiety	1/10 (10%)
Despressed mood	1/10 (10%)
Difficulty concentrating	2/10 (20%)
Feeling overwhlemed	1/10 (10%)
Irritability	4/10 (40%)
Memory impairment	1/10 (10%)
Renal and urinary disorders
Diuresis	3/10 (30%)
Respiratory, thoracic and mediastinal disorders
Chest pain on inspiration	1/10 (10%)
Dyspnea	1/10 (10%)
Exerional dyspnea	4/10 (40%)
Lung congestion	1/10 (10%)
Non-productive cough	4/10 (40%)
Productive cough	1/10 (10%)
Skin and subcutaneous tissue disorders
Alopecia	3/10 (30%)
Apthous ulcers	2/10 (20%)
Brittle nails	1/10 (10%)
Dry skin	6/10 (60%)
Local injection site reactions	9/10 (90%)
Itchiness	7/10 (70%)
Rash	6/10 (60%)
Skin tags	1/10 (10%)
Tender gums	2/10 (20%)
Vascular disorders
Vasculitis	1/10 (10%)

Limitations/Caveats

Small sample size (n=11)

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.