GEODE II: Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With Low-Dose Ribavirin QD in Subjects With Genotype 1a Chronic Hepatitis C Virus Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02609659
• Collaborator: (none)
• Enrollment: 105
• Arm: 1
• Actual Duration (Months): 14

Study Details

Study Description

Brief Summary

This study seeks to assess the safety and efficacy of treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir with low-dose ribavirin in non-cirrhotic, genotype 1a (GT1a) hepatitis C virus infected participants who are treatment-naïve or treatment-experienced with Interferon (IFN) or Pegylated Interferon (pegIFN) with or without Ribavirin (RBV).

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C Virus (HCV)	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Drug: ribavirin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 105 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With Low-Dose Ribavirin QD in Subjects With Genotype 1a Chronic Hepatitis C Virus Infection (GEODE II)
• Actual Study Start Date: Oct 28, 2015
• Actual Primary Completion Date: Oct 7, 2016
• Actual Study Completion Date: Dec 28, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 3-DAA + RBV 600 mg 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.	Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir; Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet; Other Names: Viekira Pak paritaprevir also known as ABT-450 ombitasvir also known as ABT-267 dasabuvir also known as ABT-333 ; Drug: ribavirin; Tablet

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after the last actual dose of study drug]

   SVR12 was defined as plasma 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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in participants in the treatment arm 3-DAA + RBV 600 mg) for 12 weeks compared with the historical control rate for subjects treated with 3-DAA + weight-based RBV for 12 weeks.

2. Percentage of Participants With Hemoglobin < 10 g/dL During Treatment [up to 12 weeks]

   The percentage of participants with hemoglobin <10 g/dL during treatment is provided.

3. Mean Change in Hemoglobin Values From Baseline to End of Treatment [Baseline (Day 1) to Weeks 2, 4, 8, and 12, and the Final Treatment Visit (up to 12 weeks)]

   The mean change in hemoglobin (g/L) from baseline to each study visit and to the final treatment visit (up to 12 weeks) is provided.

Secondary Outcome Measures

1. Percentage of Participants With On-treatment Virologic Failure [Up to 12 weeks]

   On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of treatment.

2. Percentage of Participants With Post-treatment Relapse [From the end of treatment through 12 weeks after the last dose of study drug]

   Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug, excluding reinfection, among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Chronic hepatitis C virus (HCV) infection

• Non-cirrhotic subjects

• Screening laboratory results showing HCV Genotype 1a (HCV GT1a) infection

• HCV treatment-naïve or if treated previously, only with interferon (IFN) or pegylated interferon (pegINF) with or without ribavirin (RBV)

Exclusion Criteria:

• Pregnant or breastfeeding women

• Positive for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab)

• HCV genotype of any subtype other than GT1a or unable to subtype

• Prior or current use of any investigational or commercially available anti-HCV agents other than IFN, pegIFN or RBV. Subjects with previous participation in trials of investigational direct-acting antiviral agents (DAAs) may be enrolled if they can produce documentation that they received only placebo.

• Current enrollment in another interventional clinical study or receipt of any investigational product within 6 weeks prior to study drug administration.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02609659
• Other Study ID Numbers: M15-582
• First Posted: Nov 20, 2015
• Last Update Posted: Dec 10, 2019
• Last Verified: Sep 1, 2017

• Keywords provided by AbbVie: Chronic Hepatitis C Infection
• Additional relevant MeSH terms: Infections; Hepatitis A; Virus Diseases; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Period Title: Overall Study
STARTED	105
COMPLETED	97
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Overall Participants	105
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.8 (13.03)
Sex: Female, Male (Count of Participants)
Female	55 52.4%
Male	50 47.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Description	SVR12 was defined as plasma 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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in participants in the treatment arm 3-DAA + RBV 600 mg) for 12 weeks compared with the historical control rate for subjects treated with 3-DAA + weight-based RBV for 12 weeks.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat population: all participants who received at least 1 dose of study drug; participants with missing data after flanking imputation were counted as nonresponders.

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Measure Participants	105
Number (95% Confidence Interval) [percentage of participants]	89.5 85.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	3-DAA + RBV 600 mg
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the 3-DAA + RBV 600 mg treatment group as compared with the historical rate for 3-DAA + weight-based RBV was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 92% to achieve noninferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	percentage of participants
	Estimated Value	89.5
	Confidence Interval	(2-Sided) 95%; 83.7 to 95.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Hemoglobin < 10 g/dL During Treatment
Description	The percentage of participants with hemoglobin <10 g/dL during treatment is provided.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (ITT population) with at least one post-baseline hemoglobin value through the final treatment value.

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Measure Participants	104
Number [percentage of participants]	0 0%

3. Primary Outcome

Title	Mean Change in Hemoglobin Values From Baseline to End of Treatment
Description	The mean change in hemoglobin (g/L) from baseline to each study visit and to the final treatment visit (up to 12 weeks) is provided.
Time Frame	Baseline (Day 1) to Weeks 2, 4, 8, and 12, and the Final Treatment Visit (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (ITT population) with a hemoglobin value at baseline and at given timepoint.

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Measure Participants	104
Week 2	-6.4 (8.17)
Week 4	-8.9 (9.37)
Week 8	-11.2 (9.85)
Week 12	-12.4 (10.06)
Final Treatment Visit	-12.1 (9.90)

4. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Failure
Description	On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of treatment.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug (ITT population).

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Measure Participants	105
Number [percentage of participants]	1.0 1%

5. Secondary Outcome

Title	Percentage of Participants With Post-treatment Relapse
Description	Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug, excluding reinfection, among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment.
Time Frame	From the end of treatment through 12 weeks after the last dose of study drug

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA <LLOQ at the final treatment visit.

Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
Measure Participants	97
Number [percentage of participants]	4.1 3.9%

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) and serious adverse events (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 or serious adverse event that begins or worsens in severity after initiation of study drug until 30 days after the last dose of study drug.
Arm/Group Title	3-DAA + RBV 600 mg
Arm/Group Description	3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) plus RBV (ribavirin [600 mg once daily]) for 12 weeks.
All Cause Mortality
	3-DAA + RBV 600 mg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	3-DAA + RBV 600 mg
	Affected / at Risk (%)	# Events
Total	3/105 (2.9%)
Gastrointestinal disorders
CYCLIC VOMITING SYNDROME	1/105 (1%)
Psychiatric disorders
BIPOLAR I DISORDER	1/105 (1%)
PSYCHOTIC DISORDER	1/105 (1%)
Other (Not Including Serious) Adverse Events
	3-DAA + RBV 600 mg
	Affected / at Risk (%)	# Events
Total	53/105 (50.5%)
Gastrointestinal disorders
CONSTIPATION	6/105 (5.7%)
DIARRHOEA	9/105 (8.6%)
NAUSEA	11/105 (10.5%)
General disorders
FATIGUE	29/105 (27.6%)
Infections and infestations
INFLUENZA	6/105 (5.7%)
Musculoskeletal and connective tissue disorders
BACK PAIN	6/105 (5.7%)
Nervous system disorders
HEADACHE	14/105 (13.3%)
Psychiatric disorders
ANXIETY	7/105 (6.7%)
INSOMNIA	12/105 (11.4%)

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.