Real World Study: Genotype 1 Chronic Hepatitis C Virus Treatment and Evaluation of Real World SVR and PRO

• Sponsor: Kaiser Permanente (Other)
• Overall Status: Completed
• CT.gov ID: NCT02461745
• Collaborator: AbbVie (Industry)
• Enrollment: 200
• Locations: 4
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 50
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

This is a Phase IV, open-label, multi-center study to evaluate the real world sustained virological response rate, subject adherence, and subject reported outcomes during and after treatment of non-cirrhotic genotype 1 chronic hepatitis C subjects aged 18 years and older, with VIEKIRA PAK (ombitasvir, paritaprevir/r, dasabuvir), with or without RBV (ribavirin).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: ombitasvir, paritaprevir/r, dasabuvir + ribavirin; Drug: ombitasvir, paritaprevir/r, dasabuvir	Phase 4

Detailed Description

This is a Phase IV, open-label, multi-center study to evaluate the real world sustained virological response rate, subject adherence, and subject reported outcomes during and after treatment of non-cirrhotic genotype 1 chronic hepatitis C subjects aged 18 years and older, with the AbbVie 3 direct-acting antiviral (3-DAA) regimen of VIEKIRA PAK (ombitasvir, paritaprevir/r, dasabuvir), with or without RBV (ribavirin).

Subjects may be treatment-naïve or treatment experienced with pegylated-interferon based regimens excluding regimens with direct-acting antiviral agents. The study will be conducted at multiple Kaiser Permanente Southern California Medical Centers.

The primary objective of this open label study is to evaluate the rate of sustained virological response rate 12 weeks after completion of treatment (SVR12) with VIEKIRA PAK, with or without ribavirin in a large real world setting.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase IV, Multisite Study of the Treatment of Chronic Hepatitis C Virus Infection Genotype 1 in a Real World Large Health Maintenance Organization: An Evaluation of Real World Sustained Virological Response and Patient Reported Outcomes
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Genotype 1a Study participants with chronic Hepatitis C Genotype 1A receiving VIEKIRA PAK (two 12.5/75/50 mg ombitasvir, paritaprevir, ritonavir tablets, and two 250 mg dasabuvir tablets) and RBV (ribavirin tablets) for 12 weeks.	Drug: ombitasvir, paritaprevir/r, dasabuvir + ribavirin; VIEKIRA PAK (two 12.5/75/50 mg ombitasvir, paritaprevir, ritonavir tablets, and two 250 mg dasabuvir tablets) + RBV (ribavirin tablets) for 12 weeks; Other Names: VIEKIRA PAK + RBV
Active Comparator: Genotype 1b Study participants with chronic Hepatitis C Genotype 1B receiving VIEKIRA PAK (two 12.5/75/50 mg ombitasvir, paritaprevir, ritonavir tablets, and two 250 mg dasabuvir tablets) for 12 weeks.	Drug: ombitasvir, paritaprevir/r, dasabuvir; VIEKIRA PAK (two 12.5/75/50 mg ombitasvir, paritaprevir, ritonavir tablets, and two 250 mg dasabuvir tablets); Other Names: VIEKIRA PAK

Outcome Measures

Primary Outcome Measures

1. Sustained Virological Response (SVR) at Week 12 [12 weeks]

   Percentage of study participants achieving sustained virological response (SVR) at Week 12 per protocol among study participants who completed 12-week course of treatment.

Secondary Outcome Measures

1. Sustained Virological Response (SVR) at Week 4 [4 weeks]

   Percentage of study participants achieving sustained virological response (SVR) at Week 4 per protocol among subjects who completed 12-week course of treatment in the study.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria

• Male or female at least 18 years of age at time of screening.

• Subject, if female must not use estrogen-containing hormonal contraception including oral, injectable, implantable, patch and ring varieties during study drug treatment

• Subject, if male, who is not surgically sterile and is sexually active with female partner of childbearing potential must agree to practice 2 effective contraceptive methods for study duration

• Subject must have at least one of the following indicators of chronic hepatitis C virus infection prior to study enrollment: Positive anti-HCV antibody or HCV RNA > 10,000 IU/mL at least 6 months before screening, and positive for HCV RNA at the time of screening, or HCV RNA > 10,000 IU/mL at screening and liver biopsy consistent with chronic HCV infection

• Subject has a screening laboratory result indicating HCV genotype 1-infection

Key Exclusion Criteria

• Subject, if female is pregnant or is breastfeeding, of if male, with female partner who is currently pregnant

• Subject has positive test result for hepatitis B surface antigen or confirmed positive anti-HIV antibody test

• Subject received study contraindicated medications prior to study drug administration

• Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inducers of cytochrome P450 2C8 (CYP2C8) or strong inhibitors of CYP2C8 within 2 weeks of the respective medication/supplement prior to initial dose of study drug.

• Clinically significant abnormalities or co-morbidities, other than HCV infection that in opinion of the investigator makes subject unsuitable for this study or drug regimen

• Current enrollment in another interventional clinical study or prior or current use of any investigational or commercially available anti-HCV agents other than interferon or ribavirin including previous exposure to ABT450 (paritaprevir) , ABT-267 (ombitasvir) or ABT-333 (dasabuvir) or receipt of any investigational product within 6 weeks prior to study drug administration

• Prior treatment of chronic HCV infection with a direct acting antiviral agent(s): telaprevir, boceprevir, sofosbuvir, simeprevir, or other direct acting antiviral

• History of solid organ transplant

• Evidence of cirrhosis

• History of liver decompensation: ascites noted on a physical exam, imaging or other test; variceal bleeding; hepatic encephalopathy

• Confirmed presence of hepatocellular carcinoma indicated on computed tomography, magnetic resonance, or other imaging techniques within 3 months prior to screening

• HCV genotype performed during screening indicates infection with any genotype other than genotype 1

• Recent history of drug or alcohol abuse that could, in the opinion of the investigator, affect adherence to the study protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Medical Center	Irvine	California	United States	92618
2	Kaiser Permanente Medical Center	Los Angeles	California	United States	90027
3	Kaiser Permanente Medical Center	San Diego	California	United States	92154
4	Kaiser Permanente Medical Center	San Marcos	California	United States	92078

Sponsors and Collaborators

• Kaiser Permanente
• AbbVie

Investigators

• Principal Investigator: Lisa M Nyberg, MD, Kaiser Permanente

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 1, 2016

More Information

Publications

None provided.

• Responsible Party: Kaiser Permanente
• ClinicalTrials.gov Identifier: NCT02461745
• Other Study ID Numbers: KPSC IRB 10568
• First Posted: Jun 3, 2015
• Last Update Posted: Jan 22, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Kaiser Permanente: VIEKIRA PAK
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ribavirin; Ritonavir

Study Results

Participant Flow

Recruitment Details	Recruitment period started in June 2015 until October 2016 at four (4) different Kaiser Permanente Southern California medical clinics.
Pre-assignment Detail	228 study participants screened for the study had 28 days from signing the study consent form to their first dose of study drug to confirm their eligibility to continue with the study. The screening period was also used as a wash-out period for concomitant medications that may interact with the study drug.

Arm/Group Title	Genotype 1a	Genotype 1b
Arm/Group Description	Study participants with chronic Hepatitis C Genotype 1a receiving VIEKIRA PAK and Ribavirin for 12 weeks.	Study participants with chronic Hepatitis C Genotype 1b receiving VIEKIRA PAK for 12 weeks.
Period Title: Overall Study
STARTED	130	70
COMPLETED	116	66
NOT COMPLETED	14	4

Baseline Characteristics

Arm/Group Title	Genotype 1a	Genotype 1b	Total
Arm/Group Description	Study participants with chronic Hepatitis C Genotype 1a receiving VIEKIRA PAK and Ribavirin for 12 weeks.	Study participants with chronic Hepatitis C Genotype 1b receiving VIEKIRA PAK for 12 weeks.	Total of all reporting groups
Overall Participants	130	70	200
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56.64	60.87	58.12
Sex: Female, Male (Count of Participants)
Female	49 37.7%	31 44.3%	80 40%
Male	81 62.3%	39 55.7%	120 60%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	5 3.8%	6 8.6%	11 5.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 1.5%	5 7.1%	7 3.5%
White	121 93.1%	56 80%	177 88.5%
More than one race	1 0.8%	2 2.9%	3 1.5%
Unknown or Not Reported	1 0.8%	1 1.4%	2 1%
Region of Enrollment (Count of Participants)
United States	130 100%	70 100%	200 100%
Baseline HCV RNA (Count of Participants)
<800,000 IU/mL	27 20.8%	17 24.3%	44 22%
Between 800,000 - 6 million	74 56.9%	43 61.4%	117 58.5%
>6 million	29 22.3%	10 14.3%	39 19.5%
Treatment-experience (Count of Participants)
Experienced	22 16.9%	9 12.9%	31 15.5%
Naive	108 83.1%	61 87.1%	169 84.5%

Outcome Measures

1. Primary Outcome

Title	Sustained Virological Response (SVR) at Week 12
Description	Percentage of study participants achieving sustained virological response (SVR) at Week 12 per protocol among study participants who completed 12-week course of treatment.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genotype 1a	Genotype 1b
Arm/Group Description	Study participants with chronic Hepatitis C Genotype 1a receiving VIEKIRA PAK and Ribavirin for 12 weeks.	Study participants with chronic Hepatitis C Genotype 1b receiving VIEKIRA PAK for 12 weeks.
Measure Participants	123	67
Count of Participants [Participants]	116 89.2%	66 94.3%

2. Secondary Outcome

Title	Sustained Virological Response (SVR) at Week 4
Description	Percentage of study participants achieving sustained virological response (SVR) at Week 4 per protocol among subjects who completed 12-week course of treatment in the study.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Genotype 1a	Genotype 1b
Arm/Group Description	Study participants with chronic Hepatitis C Genotype 1A receiving VIEKIRA PAK and Ribavirin for 12 weeks.	Study participants with chronic Hepatitis C Genotype 1B receiving VIEKIRA PAK for 12 weeks.
Measure Participants	122	66
Count of Participants [Participants]	116 89.2%	65 92.9%

Adverse Events

Time Frame	Adverse events are collected from enrolled study participants during the treatment period (12 weeks) through an additional 12 weeks post treatment. For enrolled study participants that discontinued from the study, adverse events are collected during the treatment period until their last completed study visit.
Adverse Event Reporting Description	Adverse events reported in the table below are those that are considered possibly or definitely related to the VIEKIRA PAK (ombitasvir, paritaprevir/r, dasabuvir) and/or RBV (ribavirin tablets). Although adverse events data was collected from all subjects who receive at least one dose of the study drug regardless of their relationship to either VIEKIRA PARK and/or RBV, the analysis of the safety data was focused on those that are treatment-related, which is provided below.
Arm/Group Title	Genotype 1a		Genotype 1b
Arm/Group Description	Study participants with chronic Hepatitis C Genotype 1a receiving VIEKIRA PAK and Ribavirin for 12 weeks.		Study participants with chronic Hepatitis C Genotype 1b receiving VIEKIRA PAK for 12 weeks.
All Cause Mortality
	Genotype 1a		Genotype 1b
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/130 (0%)		0/70 (0%)
Serious Adverse Events
	Genotype 1a		Genotype 1b
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/130 (3.1%)		3/70 (4.3%)
Cardiac disorders
Acute Congestive Heart Failure	1/130 (0.8%)	1	0/70 (0%)	0
Gastrointestinal disorders
Acute Pancreatitis	0/130 (0%)	0	1/70 (1.4%)	1
Infections and infestations
Cellulitis/ Sepsis	1/130 (0.8%)	1	0/70 (0%)	0
Nervous system disorders
Guillain Barre Syndrome	1/130 (0.8%)	1	0/70 (0%)	0
Psychiatric disorders
Acute Psychosis	1/130 (0.8%)	1	0/70 (0%)	0
Renal and urinary disorders
Urothelial Carcinoma	0/130 (0%)	0	1/70 (1.4%)	1
Skin and subcutaneous tissue disorders
Small Cell Carcinoma	0/130 (0%)	0	1/70 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Genotype 1a		Genotype 1b
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	102/130 (78.5%)		30/70 (42.9%)
Gastrointestinal disorders
Nausea	20/130 (15.4%)	20	4/70 (5.7%)	4
Diarrhea	5/130 (3.8%)	5	4/70 (5.7%)	4
Musculoskeletal and connective tissue disorders
Fatigue	35/130 (26.9%)	35	10/70 (14.3%)	10
Nervous system disorders
Headache	16/130 (12.3%)	16	5/70 (7.1%)	5
Insomnia	13/130 (10%)	13	1/70 (1.4%)	1
Skin and subcutaneous tissue disorders
Pruritus	7/130 (5.4%)	7	3/70 (4.3%)	3
Rash	6/130 (4.6%)	6	3/70 (4.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.