Ombitasvir/ABT-450/Ritonavir and Dasabuvir Therapy With Low Dose Ribavirin (RBV), Full Dose RBV or RBV Add-On in Treatment Naive Genotype 1a Hepatitis C Virus Infected Adults

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02493855
• Collaborator: (none)
• Enrollment: 46
• Arms: 3
• Actual Duration (Months): 18

Study Details

Study Description

Brief Summary

To evaluate the effect of ribavirin on second phase plasma hepatitis C virus (HCV) ribonucleic acid (RNA) decline in participants who receive ombitasvir/ABT-450/ritonavir and dasabuvir with full dose ribavirin, low dose ribavirin or without ribavirin for 2 weeks in treatment-naive HCV genotype (GT) 1a-infected adults.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C; Hepatitis C (HCV); Hepatitis C Genotype 1a	Drug: Ombitasvir/ABT-450/Ritonavir; Drug: Dasabuvir; Drug: Ribavirin (RBV)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study to Evaluate the Kinetics of Viral Load Decline With Ombitasvir/ABT 450/Ritonavir (Ombitasvir/ABT-450/r) and Dasabuvir Therapy With Low Dose Ribavirin (RBV), Full Dose RBV or RBV Add-On in Treatment Naïve Adults With Genotype 1a Chronic Hepatitis C Virus (HCV) Infection
• Actual Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Ribavirin Full Dose for Last 10 Weeks Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks.	Drug: Ombitasvir/ABT-450/Ritonavir; Ombitasvir/ABT-450/ritonavir combination tablets; Other Names: ABT-267/ABT-450/ritonavir ; Drug: Dasabuvir; Dasabuvir tablets; Other Names: ABT-333 ; Drug: Ribavirin (RBV); Ribavirin tablets
Experimental: Arm B: Ribavirin Full Dose for 12 Weeks Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks.	Drug: Ombitasvir/ABT-450/Ritonavir; Ombitasvir/ABT-450/ritonavir combination tablets; Other Names: ABT-267/ABT-450/ritonavir ; Drug: Dasabuvir; Dasabuvir tablets; Other Names: ABT-333 ; Drug: Ribavirin (RBV); Ribavirin tablets
Experimental: Arm C: Ribavirin Low-dose for 12 Weeks Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks.	Drug: Ombitasvir/ABT-450/Ritonavir; Ombitasvir/ABT-450/ritonavir combination tablets; Other Names: ABT-267/ABT-450/ritonavir ; Drug: Dasabuvir; Dasabuvir tablets; Other Names: ABT-333 ; Drug: Ribavirin (RBV); Ribavirin tablets

Outcome Measures

Primary Outcome Measures

1. Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment [From Week 0 to Week 2]

   HCV viral kinetics in plasma during therapy were modeled through non-linear mixed effect models, including a rapid first phase of initial decline and a slower second phase decline. The slope of the second phase decline was estimated for each treatment arm.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Screening laboratory result indicating HCV genotype 1 (GT1) a infection.

2. Chronic HCV infection.

3. Subjects must be non-cirrhotic.

4. Subjects must be able to understand and adhere to the study visit schedule and all protocol requirements as well as voluntarily sign and date an institutional review board (IRB) approved informed consent.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.

2. Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) positive immunoassay.

3. Clinically significant abnormalities or co-morbidities, other than HCV infection, that make the subject unsuitable for this study or treatment.

4. Current enrollment in another interventional clinical study. Previous use of any HCV treatments including pegylated interferon (pegIFN), ribavirin, or any direct acting antiviral agent, either investigational or approved, for HCV including protease inhibitors, nucleoside or non-nucleoside polymerase inhibitors, or nonstructural viral protein 5A (NS5A) inhibitors.

5. History or solid organ transplant.

6. Screening laboratory analysis that shows abnormal results.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: Emily Dumas, PhD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02493855
• Other Study ID Numbers: M14-242; 2014-001478-32
• First Posted: Jul 10, 2015
• Last Update Posted: Oct 31, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by AbbVie: Treatment naive; HCV; Interferon free; Hepatitis C Genotype 1a; Chronic Hepatitis C; Hepatitis C
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Recruitment Details	This study was conducted at one clinic in France and one clinic in the United States. Participants were treatment-naïve adults with hepatitis C virus (HCV) genotype (GT)1a infection without cirrhosis.
Pre-assignment Detail	Participants were randomized to Arms A or B in a 1:1 ratio first, and once those arms fully enrolled, Arm C was enrolled. Randomization to Arms A and B was stratified by site.

Arm/Group Title	Arm A: Ribavirin Full Dose for Last 10 Weeks	Arm B: Ribavirin Full Dose for 12 Weeks	Arm C: Ribavirin Low-dose for 12 Weeks
Arm/Group Description	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks.	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks.	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks.
Period Title: Overall Study
STARTED	21	19	6
COMPLETED	19	18	6
NOT COMPLETED	2	1	0

Baseline Characteristics

Arm/Group Title	Arm A: Ribavirin Full Dose for Last 10 Weeks	Arm B: Ribavirin Full Dose for 12 Weeks	Arm C: Ribavirin Low-dose for 12 Weeks	Total
Arm/Group Description	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks.	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks.	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks.	Total of all reporting groups
Overall Participants	21	19	6	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.9 (11.96)	46.0 (12.78)	36.7 (15.79)	44.3 (12.88)
Age, Customized (Count of Participants)
< 55 years	17 81%	14 73.7%	5 83.3%	36 78.3%
≥ 55 - 65 years	4 19%	5 26.3%	1 16.7%	10 21.7%
≥ 65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 52.4%	12 63.2%	4 66.7%	27 58.7%
Male	10 47.6%	7 36.8%	2 33.3%	19 41.3%
Race/Ethnicity, Customized (Count of Participants)
White	16 76.2%	14 73.7%	4 66.7%	34 73.9%
Black of African American	4 19%	3 15.8%	1 16.7%	8 17.4%
Asian	0 0%	0 0%	0 0%	0 0%
American Indian or Alaskan Native	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Mutli Race	1 4.8%	2 10.5%	1 16.7%	4 8.7%

Outcome Measures

1. Primary Outcome

Title	Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment
Description	HCV viral kinetics in plasma during therapy were modeled through non-linear mixed effect models, including a rapid first phase of initial decline and a slower second phase decline. The slope of the second phase decline was estimated for each treatment arm.
Time Frame	From Week 0 to Week 2

Outcome Measure Data

Analysis Population Description

Participants with evaluable HCV RNA to calculate the slope of the second phase. Three participants were excluded due to algorithm non-convergence in the non-linear modeling process.

Arm/Group Title	Arm A: Ribavirin Full Dose for Last 10 Weeks	Arm B: Ribavirin Full Dose for 12 Weeks	Arm C: Ribavirin Low-dose for 12 Weeks
Arm/Group Description	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks.	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks.	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks.
Measure Participants	20	17	6
Median (Full Range) [1/day]	0.0036	0.0046	0.0051

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A: Ribavirin Full Dose for Last 10 Weeks, Arm B: Ribavirin Full Dose for 12 Weeks
	Comments
	Type of Statistical Test	Superiority
	Comments	This study was an exploratory study to evaluate the effect of ribavirin on the slope of the second phase of HCV RNA decline in participants who received the 3-direct-acting antiviral agent regimen.
Statistical Test of Hypothesis	p-Value	0.311
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B: Ribavirin Full Dose for 12 Weeks, Arm C: Ribavirin Low-dose for 12 Weeks
	Comments
	Type of Statistical Test	Superiority
	Comments	This study was an exploratory study to evaluate the effect of ribavirin on the slope of the second phase of HCV RNA decline in participants who received the 3-direct-acting antiviral agent regimen.
Statistical Test of Hypothesis	p-Value	0.561
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Adverse Events

Time Frame	From first dose of study drug until 30 days after last dose; up to 16 weeks.
Arm/Group Title	Arm A: Ribavirin Full Dose for Last 10 Weeks		Arm B: Ribavirin Full Dose for 12 Weeks		Arm C: Ribavirin Low-dose for 12 Weeks
Arm/Group Description	Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks.		Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks.		Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks.
All Cause Mortality
	Arm A: Ribavirin Full Dose for Last 10 Weeks		Arm B: Ribavirin Full Dose for 12 Weeks		Arm C: Ribavirin Low-dose for 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A: Ribavirin Full Dose for Last 10 Weeks		Arm B: Ribavirin Full Dose for 12 Weeks		Arm C: Ribavirin Low-dose for 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/21 (4.8%)		0/19 (0%)		0/6 (0%)
Psychiatric disorders
DEPRESSION	1/21 (4.8%)		0/19 (0%)		0/6 (0%)
DRUG DEPENDENCE	1/21 (4.8%)		0/19 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Arm A: Ribavirin Full Dose for Last 10 Weeks		Arm B: Ribavirin Full Dose for 12 Weeks		Arm C: Ribavirin Low-dose for 12 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/21 (81%)		16/19 (84.2%)		6/6 (100%)
Blood and lymphatic system disorders
ANAEMIA	4/21 (19%)		4/19 (21.1%)		2/6 (33.3%)
INCREASED TENDENCY TO BRUISE	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
LYMPHADENOPATHY	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Cardiac disorders
PALPITATIONS	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Ear and labyrinth disorders
VERTIGO	0/21 (0%)		2/19 (10.5%)		0/6 (0%)
Eye disorders
DRY EYE	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	1/21 (4.8%)		1/19 (5.3%)		0/6 (0%)
ABDOMINAL PAIN	3/21 (14.3%)		3/19 (15.8%)		1/6 (16.7%)
ABDOMINAL PAIN UPPER	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
CONSTIPATION	2/21 (9.5%)		0/19 (0%)		1/6 (16.7%)
DIARRHOEA	1/21 (4.8%)		0/19 (0%)		1/6 (16.7%)
DRY MOUTH	1/21 (4.8%)		1/19 (5.3%)		2/6 (33.3%)
DYSPEPSIA	0/21 (0%)		2/19 (10.5%)		3/6 (50%)
HAEMATOCHEZIA	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
NAUSEA	3/21 (14.3%)		3/19 (15.8%)		2/6 (33.3%)
RECTAL HAEMORRHAGE	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
VOMITING	3/21 (14.3%)		0/19 (0%)		1/6 (16.7%)
General disorders
ASTHENIA	3/21 (14.3%)		3/19 (15.8%)		0/6 (0%)
FATIGUE	5/21 (23.8%)		7/19 (36.8%)		2/6 (33.3%)
FEELING ABNORMAL	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
PYREXIA	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
Hepatobiliary disorders
HYPERBILIRUBINAEMIA	2/21 (9.5%)		0/19 (0%)		2/6 (33.3%)
HYPERTRANSAMINASAEMIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Infections and infestations
BRONCHITIS	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
FUNGAL SKIN INFECTION	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
INFLUENZA	1/21 (4.8%)		0/19 (0%)		0/6 (0%)
ORAL CANDIDIASIS	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
UPPER RESPIRATORY TRACT INFECTION	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
URINARY TRACT INFECTION	1/21 (4.8%)		0/19 (0%)		1/6 (16.7%)
Injury, poisoning and procedural complications
LIMB INJURY	1/21 (4.8%)		0/19 (0%)		1/6 (16.7%)
PROCEDURAL HEADACHE	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
PROCEDURAL PAIN	7/21 (33.3%)		5/19 (26.3%)		5/6 (83.3%)
Investigations
ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
ALANINE AMINOTRANSFERASE INCREASED	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
BODY TEMPERATURE FLUCTUATION	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
GLUCOSE URINE PRESENT	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
HAEMOGLOBIN DECREASED	1/21 (4.8%)		3/19 (15.8%)		0/6 (0%)
INTERNATIONAL NORMALISED RATIO INCREASED	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
PROTHROMBIN LEVEL INCREASED	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Metabolism and nutrition disorders
DEHYDRATION	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
HYPERGLYCAEMIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
HYPERMAGNESAEMIA	0/21 (0%)		1/19 (5.3%)		1/6 (16.7%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
BACK PAIN	2/21 (9.5%)		1/19 (5.3%)		2/6 (33.3%)
FLANK PAIN	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
MUSCLE TIGHTNESS	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
MUSCULOSKELETAL CHEST PAIN	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
MUSCULOSKELETAL PAIN	2/21 (9.5%)		1/19 (5.3%)		0/6 (0%)
MYALGIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Nervous system disorders
AMNESIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
DIZZINESS	0/21 (0%)		2/19 (10.5%)		0/6 (0%)
HEADACHE	4/21 (19%)		4/19 (21.1%)		0/6 (0%)
MEMORY IMPAIRMENT	0/21 (0%)		3/19 (15.8%)		0/6 (0%)
MIGRAINE	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
SYNCOPE	1/21 (4.8%)		1/19 (5.3%)		0/6 (0%)
Psychiatric disorders
ANXIETY	1/21 (4.8%)		0/19 (0%)		1/6 (16.7%)
CONFUSIONAL STATE	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
DEPRESSED MOOD	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
DEPRESSION	3/21 (14.3%)		2/19 (10.5%)		0/6 (0%)
EMOTIONAL DISTRESS	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
INSOMNIA	3/21 (14.3%)		3/19 (15.8%)		0/6 (0%)
IRRITABILITY	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
MOOD SWINGS	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
SLEEP DISORDER	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
Renal and urinary disorders
CHROMATURIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
DYSURIA	0/21 (0%)		0/19 (0%)		1/6 (16.7%)
Reproductive system and breast disorders
POLYMENORRHOEA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
DYSPNOEA	2/21 (9.5%)		0/19 (0%)		1/6 (16.7%)
OROPHARYNGEAL PAIN	1/21 (4.8%)		1/19 (5.3%)		1/6 (16.7%)
RESPIRATORY TRACT CONGESTION	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
SINUS CONGESTION	0/21 (0%)		1/19 (5.3%)		1/6 (16.7%)
Skin and subcutaneous tissue disorders
ALOPECIA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
ANGIOEDEMA	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
DERMATITIS CONTACT	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
DRY SKIN	0/21 (0%)		2/19 (10.5%)		0/6 (0%)
PRURITUS	3/21 (14.3%)		6/19 (31.6%)		1/6 (16.7%)
RASH	0/21 (0%)		1/19 (5.3%)		2/6 (33.3%)
RASH GENERALISED	0/21 (0%)		1/19 (5.3%)		0/6 (0%)
Vascular disorders
FLUSHING	0/21 (0%)		1/19 (5.3%)		1/6 (16.7%)
HYPOTENSION	0/21 (0%)		1/19 (5.3%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.