Ombitasvir/ABT-450 (Paritaprevir)/Ritonavir With Dasabuvir and Ribavirin (RBV) in Treatment Naive and Treatment Experienced Genotype 1a Hepatitis C Virus Infected Adults

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02476617
• Collaborator: (none)
• Enrollment: 25
• Arm: 1
• Duration (Months): 18

Study Details

Study Description

Brief Summary

A study to evaluate immune restoration following removal of viral antigen in non-cirrhotic hepatitis C virus (HCV) genotype (GT) 1a treatment-naïve and pegylated-interferon (pegIFN)/ribavirin (RBV) treatment-experienced adults receiving treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir coadministered with ribavirin (RBV) for 12 weeks.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C; Hepatitis C (HCV); Hepatitis C Genotype 1a	Drug: ombitasvir/paritaprevir/ritonavir; Drug: dasabuvir; Drug: ribavirin	Phase 3

Detailed Description

A study to evaluate the role of ombitasvir/paritaprevir/ritonavir and dasabuvir coadministered with RBV treatment leading to sustained virologic response 12 weeks post-dosing (SVR12) on the changes from baseline in IFN-stimulated gene (ISG) expression in peripheral blood mononucleated cells (PBMCs) in HCV GT 1a-infected adult participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study to Evaluate Immune Restoration Following Removal of Viral Antigen in Treatment-Naïve and Treatment-Experienced Adults With Genotype (GT) 1a Chronic Hepatitis C Virus (HCV) Infection Administered Ombitasvir/ ABT-450/Ritonavir With Dasabuvir and Ribavirin (RBV) for 12 Weeks
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV Ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily [QD]) + dasabuvir (250 mg twice daily [BID]) + weight based Ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided BID)	Drug: ombitasvir/paritaprevir/ritonavir; ombitasvir/ABT-450/ritonavir tablets; Other Names: ABT-267/ABT-450/ritonavir ; Drug: dasabuvir; dasabuvir tablets; Other Names: ABT-333 ; Drug: ribavirin; ribavirin tablets

Outcome Measures

Primary Outcome Measures

1. Change in Interferon (IFN)-Stimulated Genes (ISG) Expression in Peripheral Blood Mononucleated Cells (PBMCs) for Participants Achieving SVR12 [Week 0 to Post-Treatment Week 12]

   The changes from week 0 to post-treatment (PT) week 12 in key ISG expression in PBMCs for participants achieving sustained virologic response 12 weeks PT (SVR12) where SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (<LLOQ) 12 weeks after the last dose of study drug. For each key ISG, fold change was defined as the ratio of the difference between PT Week 12 and baseline expressions over the baseline expression.

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 hepatitis C viral (HCV) genotype (GT) 1a infection.

2. Chronic HCV infection.

3. Participants must be non-cirrhotic.

4. Participants must be treatment-naïve or have documentation that they were adherent to prior pegIFN/RBV combination therapy and meet the criteria of prior pegylated-interferon (pegIFN)/ribavirin (RBV) treatment failure.

5. Participants must meet specific human leukocyte antigen (HLA) allele requirements.

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 enrollment in this study, prior or current use of any investigational or commercially available anti-HCV agents other than pegIFN or RBV (including previous exposure to paritaprevir, ombitasvir, or dasabuvir), or receipt of any investigational product within 6 weeks prior to study drug administration.

5. History of 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: NCT02476617
• Other Study ID Numbers: M14-243
• First Posted: Jun 19, 2015
• Last Update Posted: Oct 3, 2017
• Last Verified: Aug 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AbbVie: Treatment naive; Interferon free; HCV; Chronic Hepatitis C; Hepatitis C Genotype 1a; Hepatitis C; pegylated-interferon (pegIFN)/ribavirin (RBV) experienced
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	The intent-to-treat (ITT) population consisted of all enrolled participants who received at least one dose of study drug.

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily [QD]) + dasabuvir (250 mg twice daily [BID]) + weight based Ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided BID)
Period Title: Overall Study
STARTED	25
COMPLETED	23
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg QD) + dasabuvir (250 mg BID) + weight based Ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided BID)
Overall Participants	25
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (12.61)
Sex: Female, Male (Count of Participants)
Female	6 24%
Male	19 76%

Outcome Measures

1. Primary Outcome

Title	Change in Interferon (IFN)-Stimulated Genes (ISG) Expression in Peripheral Blood Mononucleated Cells (PBMCs) for Participants Achieving SVR12
Description	The changes from week 0 to post-treatment (PT) week 12 in key ISG expression in PBMCs for participants achieving sustained virologic response 12 weeks PT (SVR12) where SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (<LLOQ) 12 weeks after the last dose of study drug. For each key ISG, fold change was defined as the ratio of the difference between PT Week 12 and baseline expressions over the baseline expression.
Time Frame	Week 0 to Post-Treatment Week 12

Outcome Measure Data

Analysis Population Description

All participants who achieved SVR12 and had both baseline and post-baseline value at Post-Treatment Week 12 were included in this analyses..

Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
Arm/Group Description	Ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg QD) + dasabuvir (250 mg BID) + weight based Ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided BID)
Measure Participants	21
CXCL10	-0.464 (0.6143)
ISG15	-0.148 (0.7458)
CXCL11	-0.611 (0.3090)
MX1	-0.399 (0.3013)
IFI27	-0.462 (0.4624)
OAS2	-0.168 (0.5168)
DDX60	-0.016 (0.5696)
IFIT3	-0.543 (0.3350)
IFI44	-0.467 (0.2569)
STAT1	-0.301 (0.3430)
CXCL9	-0.552 (0.2816)
IFIT1	-0.440 (0.4441)
HERC5	-0.358 (0.2827)
IRF7	-0.171 (0.4273)
OAS1	0.284 (1.4668)
PLSCR1	-0.255 (0.3688)
IRF9	-0.205 (0.2809)
IFIH1	-0.321 (0.3213)
TRIM14	0.022 (0.5282)
IRF1	-0.130 (0.6497)
IRF3	0.044 (0.6307)
STAT2	-0.051 (0.5762)
IFNG	0.516 (1.4653)
IFNL1	-0.361 (0.3753)
IFNL2	-0.199 (0.7031)
IFNL3	-0.205 (0.4306)
IFNL4	-0.228 (0.7298)
IFNGR1	-0.046 (0.3008)
ADAR	-0.212 (0.2314)
ALG10	-0.083 (0.7491)
BCHE	-0.101 (0.5739)
CCL2	0.200 (1.5071)
CCL4	0.638 (1.7396)
CD163	0.556 (2.7478)
CXCL5	1.085 (2.7539)
CXCR3	0.308 (0.5236)
DDIT4	0.029 (1.2134)
DDX58	0.388 (1.2231)
DPP4	0.869 (1.5730)
EIF2AK2	-0.317 (0.2521)
GBP1	-0.288 (0.4421)
GCKR	0.009 (0.5267)
GUCY1B3	0.350 (0.7909)
HELZ2	-0.232 (0.5124)
HERC6	-0.074 (0.3294)
IFI35	-0.023 (0.6428)
IFI44L	-0.554 (0.4068)
IFI6	-0.464 (0.3010)
IFIT2	-0.365 (0.4118)
IFIT5	-0.291 (0.2085)
IFITM1	-0.066 (0.3696)
IFITM2	0.158 (0.7905)
IFITM3	-0.423 (0.3313)
IFNA	-0.202 (0.5037)
IFNB	-0.167 (0.4427)
IL10	0.202 (0.8216)
IL18	-0.078 (0.2695)
IRF2	0.311 (1.0487)
ISG20	0.156 (1.0071)
MAP3K14	-0.072 (0.2983)
MOV10	-0.185 (0.4048)
MS4A4A	-0.005 (0.7458)
MX2	-0.101 (0.6188)
MYST1	-0.057 (0.2404)
NOS2A	0.249 (0.8288)
NT5C3	0.017 (0.3577)
OASL	-0.233 (0.6984)
PPP3CB	0.011 (0.1956)
RNASEL	0.395 (0.9973)
RSAD2	-0.406 (0.3202)
SLC27A2	0.022 (0.9149)
SOCS1	1.313 (3.5778)
SOCS3	0.025 (1.1773)
USP18	-0.288 (0.3092)

Adverse Events

Time Frame	Treatment-emergent AEs (TEAEs) and treatment-emergent SAEs (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 16 weeks).
Adverse Event Reporting Description	TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
Arm/Group Title	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
Arm/Group Description	Arm/Group Description: Ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg QD) + dasabuvir (250 mg BID) + weight based Ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided BID)
All Cause Mortality
	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
	Affected / at Risk (%)	# Events
Total	2/25 (8%)
Injury, poisoning and procedural complications
OVERDOSE	1/25 (4%)
Psychiatric disorders
ANXIETY	1/25 (4%)
Other (Not Including Serious) Adverse Events
	Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir + RBV
	Affected / at Risk (%)	# Events
Total	24/25 (96%)
Ear and labyrinth disorders
EXCESSIVE CERUMEN PRODUCTION	1/25 (4%)
VERTIGO	1/25 (4%)
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	3/25 (12%)
ABDOMINAL PAIN UPPER	1/25 (4%)
CONSTIPATION	4/25 (16%)
DIARRHOEA	5/25 (20%)
DYSPEPSIA	4/25 (16%)
DYSPHAGIA	1/25 (4%)
ERUCTATION	1/25 (4%)
FAECES DISCOLOURED	2/25 (8%)
HAEMATOCHEZIA	1/25 (4%)
IRRITABLE BOWEL SYNDROME	1/25 (4%)
NAUSEA	9/25 (36%)
RETCHING	2/25 (8%)
VOMITING	3/25 (12%)
General disorders
ASTHENIA	3/25 (12%)
CHEST DISCOMFORT	1/25 (4%)
CHEST PAIN	1/25 (4%)
CYST	1/25 (4%)
FATIGUE	16/25 (64%)
FEELING JITTERY	1/25 (4%)
MALAISE	3/25 (12%)
PAIN	1/25 (4%)
PERIPHERAL SWELLING	2/25 (8%)
Hepatobiliary disorders
BILIARY DILATATION	1/25 (4%)
Immune system disorders
HYPERSENSITIVITY	2/25 (8%)
Infections and infestations
BRONCHITIS	1/25 (4%)
EAR INFECTION	1/25 (4%)
GASTROENTERITIS VIRAL	2/25 (8%)
HERPES ZOSTER	1/25 (4%)
INFECTED DERMAL CYST	1/25 (4%)
INFLUENZA	2/25 (8%)
NASOPHARYNGITIS	3/25 (12%)
SINUSITIS	1/25 (4%)
TOOTH INFECTION	1/25 (4%)
Injury, poisoning and procedural complications
HAND FRACTURE	1/25 (4%)
JOINT DISLOCATION	1/25 (4%)
LIGAMENT SPRAIN	1/25 (4%)
MUSCLE STRAIN	1/25 (4%)
ROAD TRAFFIC ACCIDENT	1/25 (4%)
Investigations
BLOOD BILIRUBIN INCREASED	4/25 (16%)
CREATININE RENAL CLEARANCE DECREASED	1/25 (4%)
HAEMATOCRIT DECREASED	1/25 (4%)
HAEMOGLOBIN DECREASED	4/25 (16%)
Metabolism and nutrition disorders
DECREASED APPETITE	3/25 (12%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	2/25 (8%)
ARTHRITIS	1/25 (4%)
BACK PAIN	1/25 (4%)
FLANK PAIN	1/25 (4%)
MUSCULOSKELETAL STIFFNESS	1/25 (4%)
MYALGIA	3/25 (12%)
PAIN IN EXTREMITY	1/25 (4%)
SPINAL COLUMN STENOSIS	1/25 (4%)
Nervous system disorders
BURNING SENSATION	1/25 (4%)
DIZZINESS	4/25 (16%)
DYSGEUSIA	1/25 (4%)
HEADACHE	6/25 (24%)
HYPOAESTHESIA	2/25 (8%)
LOSS OF CONSCIOUSNESS	1/25 (4%)
PARAESTHESIA	1/25 (4%)
POOR QUALITY SLEEP	2/25 (8%)
RESTLESS LEGS SYNDROME	2/25 (8%)
SYNCOPE	1/25 (4%)
Psychiatric disorders
ANXIETY	4/25 (16%)
DEPRESSION	1/25 (4%)
INSOMNIA	6/25 (24%)
IRRITABILITY	4/25 (16%)
MOOD SWINGS	1/25 (4%)
TACHYPHRENIA	1/25 (4%)
Renal and urinary disorders
CHROMATURIA	1/25 (4%)
NEPHROLITHIASIS	1/25 (4%)
Respiratory, thoracic and mediastinal disorders
COUGH	1/25 (4%)
DYSPNOEA	4/25 (16%)
HAEMOPTYSIS	1/25 (4%)
NASAL CONGESTION	2/25 (8%)
OROPHARYNGEAL PAIN	1/25 (4%)
Skin and subcutaneous tissue disorders
HYPERHIDROSIS	1/25 (4%)
PRURITUS	3/25 (12%)
PSORIASIS	1/25 (4%)
RASH	3/25 (12%)
SKIN IRRITATION	1/25 (4%)

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.