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A Study to Evaluate the Safety and Effect of the Experimental Drugs ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Subjects With Chronic Hepatitis C (PEARL-II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01674725
Recruitment Status : Completed
First Posted : August 29, 2012
Results First Posted : January 6, 2015
Last Update Posted : November 10, 2015
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Hepatitis C Infection
Interventions Drug: ABT-450/r/ABT-267, ABT-333
Drug: Ribavirin
Enrollment 187
Recruitment Details  
Pre-assignment Details  
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
Period Title: Overall Study
Started 92 95
Completed 89 94
Not Completed 3 1
Reason Not Completed
Adverse Event             1             0
Did not receive study drug             1             0
Withdrawal by Subject             1             0
Lost to Follow-up             0             1
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333 Total
Hide Arm/Group Description ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 91 95 186
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 91 participants 95 participants 186 participants
54.2  (10.90) 54.2  (10.51) 54.2  (10.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 91 participants 95 participants 186 participants
Female
46
  50.5%
38
  40.0%
84
  45.2%
Male
45
  49.5%
57
  60.0%
102
  54.8%
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Primary Analyses
Hide Description

The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.

The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b infection treated with telaprevir and peginterferon (pegIFN)/RBV.

Time Frame 12 weeks after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HCV subgenotype 1B (GT1b) infection who received at least 1 dose of coformulated ABT-450/r/ABT-267 and ABT-333, with or without RBV (intent-to-treat [ITT GT1b] population); participants with missing data were counted as non-responders.
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description:
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
Overall Number of Participants Analyzed 88 91
Measure Type: Number
Unit of Measure: percentage of participants
97.7 100
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABT-450/r/ABT-267 and ABT-333
Comments Planned enrollment is 210 to allow ≥200 GT1b-infected participants to be treated with combination formulation of ABT-450/r/ABT-267 and ABT-333 with and without RBV. Enrollment terminated after 187 participants were randomized. Assuming a rate of 82% in each arm, a sample size of 90 participants per arm will have >90% power to demonstrate noninferiority of each arm to the historical rate based on the normal approximation of a single binomial proportion in a one-sample test for superiority.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333 treatment group as compared with the historical rate for telaprevir plus pegIFN-RBV was analyzed; the lower confidence bound of the 2-sided 95% confidence interval for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 64% to achieve noninferiority.
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 100
Confidence Interval (2-Sided) 95%
95.9 to 100.0
Estimation Comments 95% CI was calculated using the Wilson score method for the single proportion because the point estimate was 100%.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABT-450/r/ABT-267 and ABT-333, Plus RBV
Comments Assuming a rate of 82% in each arm, a sample size of 90 participants per arm will have >90% power to demonstrate noninferiority of each arm to the historical rate based on the normal approximation of a single binomial proportion in a one-sample test for superiority.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group as compared with the historical rate for telaprevir plus pegIFN-RBV was analyzed; the lower confidence bound of the 2-sided 95% confidence interval for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 64% to achieve noninferiority.
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 97.7
Confidence Interval (2-Sided) 95%
94.6 to 100.0
Estimation Comments 95% CI was calculated using the normal approximation to the binomial distribution.
2.Secondary Outcome
Title Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment
Hide Description The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment.
Time Frame Baseline (Day 1) and Week 12 (End of Treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HCV subgenotype 1B (GT1b) infection who received at least 1 dose of coformulated ABT-450/r/ABT-267 and ABT-333, with or without RBV (intent-to-treat [ITT GT1b]) and had hemoglobin ≥ LLN reference range at baseline.
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description:
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
Overall Number of Participants Analyzed 88 91
Measure Type: Number
Unit of Measure: percentage of participants
42.0 5.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABT-450/r/ABT-267 and ABT-333, Plus RBV, ABT-450/r/ABT-267 and ABT-333
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Secondary Analyses
Hide Description

The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.

The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b treated with telaprevir and pegIFN/RBV; and the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333 compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV.

Time Frame 12 weeks after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HCV subgenotype 1B (GT1b) infection who received at least 1 dose of coformulated ABT-450/r/ABT-267 and ABT-333, with or without RBV (intent-to-treat [ITT GT1b] population); participants with missing data were counted as non-responders.
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description:
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
Overall Number of Participants Analyzed 88 91
Measure Type: Number
Unit of Measure: percentage of participants
97.7 100
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABT-450/r/ABT-267 and ABT-333, Plus RBV
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 97.7
Confidence Interval (2-Sided) 95%
94.6 to 100.0
Estimation Comments 95% CI was calculated using the normal approximation to the binomial distribution; the lower confidence bound for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 75% to achieve superiority.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ABT-450/r/ABT-267 and ABT-333
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 100
Confidence Interval (2-Sided) 95%
95.9 to 100
Estimation Comments 95% CI was calculated using the Wilson score method for the single proportion; the lower confidence bound for the percentage of participants with sustained virologic response at 12 weeks after treatment must exceed 75% to achieve superiority
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ABT-450/r/ABT-267 and ABT-333, Plus RBV, ABT-450/r/ABT-267 and ABT-333
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333 treatment group as compared with the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group was analyzed using a noninferiority margin of -10.5%; the lower confidence bound of the 2-sided 95% confidence interval for the difference in percentage of participants with sustained virologic response at 12 weeks after treatment must exceed -10.5% to achieve noninferiority.
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-0.8 to 5.4
Estimation Comments 95% CI was calculated using the normal approximation to the binomial distribution.
4.Secondary Outcome
Title Percentage of Participants With Virologic Failure During Treatment
Hide Description Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment).
Time Frame Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HCV subgenotype 1B (GT1b) infection who received at least 1 dose of coformulated ABT-450/r/ABT-267 and ABT-333, with or without RBV (intent-to-treat [ITT GT1b] population).
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description:
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
Overall Number of Participants Analyzed 88 91
Measure Type: Number
Unit of Measure: percentage of participants
Rebound 0 0
Failure to Suppress 0 0
5.Secondary Outcome
Title Percentage of Participants With Virologic Relapse After Treatment
Hide Description Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period. 95% CI was calculated using the Wilson score method for the single proportion because the point estimate was 0%.
Time Frame Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-Treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HCV subgenotype 1B (GT1b) infection who received at least 1 dose of coformulated ABT-450/r/ABT-267 and ABT-333, with or without RBV (ITT GT1b population) with HCV RNA < LLOQ at the final treatment visit and completed treatment.
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description:
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
Overall Number of Participants Analyzed 86 91
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0.0 to 4.3)
0
(0.0 to 4.1)
Time Frame AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of participation in the study (up to 64 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Hide Arm/Group Description ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks
All-Cause Mortality
ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Affected / at Risk (%) Affected / at Risk (%)
Total   2/91 (2.20%)   2/95 (2.11%) 
Gastrointestinal disorders     
PANCREATITIS  1  1/91 (1.10%)  0/95 (0.00%) 
Infections and infestations     
CELLULITIS  1  0/91 (0.00%)  1/95 (1.05%) 
Musculoskeletal and connective tissue disorders     
OSTEOARTHRITIS  1  1/91 (1.10%)  0/95 (0.00%) 
Renal and urinary disorders     
NEPHROLITHIASIS  1  0/91 (0.00%)  1/95 (1.05%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ABT-450/r/ABT-267 and ABT-333, Plus RBV ABT-450/r/ABT-267 and ABT-333
Affected / at Risk (%) Affected / at Risk (%)
Total   71/91 (78.02%)   62/95 (65.26%) 
Blood and lymphatic system disorders     
ANAEMIA  1  10/91 (10.99%)  0/95 (0.00%) 
Cardiac disorders     
PALPITATIONS  1  5/91 (5.49%)  2/95 (2.11%) 
Gastrointestinal disorders     
CONSTIPATION  1  5/91 (5.49%)  1/95 (1.05%) 
DIARRHOEA  1  12/91 (13.19%)  12/95 (12.63%) 
NAUSEA  1  19/91 (20.88%)  6/95 (6.32%) 
General disorders     
ASTHENIA  1  11/91 (12.09%)  7/95 (7.37%) 
FATIGUE  1  29/91 (31.87%)  16/95 (16.84%) 
IRRITABILITY  1  5/91 (5.49%)  1/95 (1.05%) 
PYREXIA  1  6/91 (6.59%)  8/95 (8.42%) 
Hepatobiliary disorders     
HYPERBILIRUBINAEMIA  1  5/91 (5.49%)  2/95 (2.11%) 
Infections and infestations     
INFLUENZA  1  2/91 (2.20%)  6/95 (6.32%) 
NASOPHARYNGITIS  1  6/91 (6.59%)  6/95 (6.32%) 
Investigations     
BLOOD BILIRUBIN INCREASED  1  8/91 (8.79%)  0/95 (0.00%) 
Metabolism and nutrition disorders     
DECREASED APPETITE  1  9/91 (9.89%)  2/95 (2.11%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  6/91 (6.59%)  6/95 (6.32%) 
MYALGIA  1  6/91 (6.59%)  4/95 (4.21%) 
Nervous system disorders     
DIZZINESS  1  8/91 (8.79%)  3/95 (3.16%) 
HEADACHE  1  22/91 (24.18%)  22/95 (23.16%) 
Psychiatric disorders     
INSOMNIA  1  13/91 (14.29%)  3/95 (3.16%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  3/91 (3.30%)  7/95 (7.37%) 
DYSPNOEA  1  8/91 (8.79%)  2/95 (2.11%) 
DYSPNOEA EXERTIONAL  1  5/91 (5.49%)  1/95 (1.05%) 
Skin and subcutaneous tissue disorders     
PRURITUS  1  13/91 (14.29%)  8/95 (8.42%) 
RASH  1  8/91 (8.79%)  1/95 (1.05%) 
Vascular disorders     
HYPERTENSION  1  5/91 (5.49%)  4/95 (4.21%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Information
Organization: AbbVie
Phone: 800-633-9110
Layout table for additonal information
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01674725    
Other Study ID Numbers: M13-389
2011-005740-95 ( EudraCT Number )
First Submitted: July 27, 2012
First Posted: August 29, 2012
Results First Submitted: December 23, 2014
Results First Posted: January 6, 2015
Last Update Posted: November 10, 2015