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A Study to Evaluate the Efficacy and Safety of Three Experimental Drugs Compared With Telaprevir (a Licensed Product) for Treatment of Chronic Hepatitis C Infection in Treatment-experienced Adults (MALACHITE 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: NCT01854528
Recruitment Status : Completed
First Posted : May 15, 2013
Results First Posted : February 11, 2016
Last Update Posted : June 6, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie

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
Drug: Pegylated Interferon a-2a (PegINF)
Drug: Telaprevir
Enrollment 148
Recruitment Details  
Pre-assignment Details A total of 154 participants were randomized: 6 participants did not receive at least 1 dose of study drug and were excluded from the analyses; 148 participants received at least 1 dose and were included in the intent-to-treat (ITT) population.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description 3-DAA (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. TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Period Title: Overall Study
Started 101 47
Completed 101 32
Not Completed 0 15
Reason Not Completed
Adverse Event             0             4
Withdrawal by Subject             0             2
Virologic Failure             0             9
Arm/Group Title 3-DAA/RBV TPV/RBV Total
Hide Arm/Group Description 3-DAA (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. TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information. Total of all reporting groups
Overall Number of Baseline Participants 101 47 148
Hide Baseline Analysis Population Description
All randomized participants who received at least 1 dose of study drug (ITT population) were included in baseline analysis population.
Age, Continuous  
Median (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 47 participants 148 participants
46.9  (12.15) 45.0  (10.35) 46.3  (11.61)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 47 participants 148 participants
Female
46
  45.5%
19
  40.4%
65
  43.9%
Male
55
  54.5%
28
  59.6%
83
  56.1%
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment
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.
Time Frame 12 weeks after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population: All randomized participants who received at least 1 dose of study drug.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description:
3-DAA (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.
TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Overall Number of Participants Analyzed 101 47
Measure Type: Number
Unit of Measure: percentage of participants
100.0 66.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3-DAA/RBV, TPV/RBV
Comments P-value for the difference in sustained virologic response rates 12 weeks after the last dose between treatment groups with HCV subgenotype (1a, non-1a) from stratum adjusted Mantel-Haenszel with previous type of response to pegIFN/RBV treatment (relapser, partial or null responder) as strata.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Stratum adjusted Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 34.26
Confidence Interval (2-Sided) 95%
21.09 to 47.42
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline to Final Treatment Visit in the Mental Component Summary (MCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2)
Hide Description The SF-36v2 is a general health-related quality of life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises a total of 36 items (questions) targeting a participant's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Domain scores were aggregated into an MCS score (from 0 to 100; a higher score indicates better mental function and well-being).
Time Frame Baseline and Final Treatment Visit (up to Week 12 for 3-DAA/RBV and up to Week 24 or 48 for TPV/RBV)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population with evaluable data.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description:
3-DAA (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.
TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Overall Number of Participants Analyzed 101 45
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.3  (8.32) -9.8  (11.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3-DAA/RBV, TPV/RBV
Comments P-value from ANCOVA model including baseline score and region as covariates and treatment arm as a factor.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 8.64
Confidence Interval (2-Sided) 95%
5.43 to 11.85
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline to Final Treatment Visit in the Physical Component Summary (PCS) Score of the Short-Form 36 Health Survey - Version 2 (SF-36v2)
Hide Description The SF-36v2 is a general health-related quality of life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises a total of 36 items (questions) targeting a participant's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Domain scores were aggregated into a PCS score (range = 0 to 100; a higher score indicates better mental function and well-being).
Time Frame Baseline and Final Treatment Visit (up to Week 12 for 3-DAA/RBV and up to Week 24 or 48 for TPV/RBV)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population with evaluable data.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description:
3-DAA (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.
TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Overall Number of Participants Analyzed 101 45
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.4  (7.16) -7.7  (7.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3-DAA/RBV, TPV/RBV
Comments P-value from ANCOVA model including baseline score and region as covariates and treatment arm as a factor.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 7.55
Confidence Interval (2-Sided) 95%
5.11 to 9.98
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment
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]) 24 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.
Time Frame 24 weeks after the last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population with evaluable data.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description:
3-DAA (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.
TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Overall Number of Participants Analyzed 101 47
Measure Type: Number
Unit of Measure: percentage of participants
99.0 66.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 3-DAA/RBV, TPV/RBV
Comments P-value from logistic regression model including treatment arm, baseline log10 HCV RNA level, HCV subgenotype, and previous response to pegIFN/RBV treatment as predictors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 54.7
Confidence Interval (2-Sided) 95%
6.9 to 435.1
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Virologic Failure During Treatment
Hide Description Virologic failure during treatment was defined as HCV ribonucleic acid (RNA) confirmed greater than or equal to the lower limit of quantification (≥ LLOQ) after HCV RNA < LLOQ during treatment or confirmed HCV RNA ≥ LLOQ at the end of treatment.
Time Frame Baseline to end of treatment (12 weeks for 3-DAA/RBV and 24 or 48 weeks for TPV/RBV)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description:
3-DAA (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.
TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Overall Number of Participants Analyzed 101 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0.0 to 3.7)
19.1
(7.9 to 30.4)
6.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.
Time Frame Between end of treatment (Week 12 for 3-DAA/RBV and Week 24 or 48 for TPV/RBV) and Post-treatment (up to Week 12 Post-treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description:
3-DAA (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.
TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
Overall Number of Participants Analyzed 101 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0
(0.0 to 3.7)
6.3
(0.0 to 14.6)
Time Frame AEs were collected from the time of study drug administration to 30 days after last dose of study drug (up to 52 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (total up to 101 weeks).
Adverse Event Reporting Description AEs were collected from first dose to 30 days after last dose (16 weeks for 12-week treatment, 28 weeks for 24-week treatment, 52 weeks for 48-week treatment); SAEs were collected from the time that informed consent was obtained to end of study (up to 65 weeks for 12-week treatment, 77 weeks for 24-week treatment, 101 weeks for 48-week treatment).
 
Arm/Group Title 3-DAA/RBV TPV/RBV
Hide Arm/Group Description 3-DAA (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. TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously [SC] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information.
All-Cause Mortality
3-DAA/RBV TPV/RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
3-DAA/RBV TPV/RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   1/101 (0.99%)   5/47 (10.64%) 
Blood and lymphatic system disorders     
ANAEMIA  1  0/101 (0.00%)  2/47 (4.26%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  0/101 (0.00%)  1/47 (2.13%) 
General disorders     
INJECTION SITE PHLEBITIS  1  0/101 (0.00%)  1/47 (2.13%) 
Infections and infestations     
APPENDICITIS  1  1/101 (0.99%)  0/47 (0.00%) 
DIARRHOEA INFECTIOUS  1  0/101 (0.00%)  1/47 (2.13%) 
STAPHYLOCOCCAL SEPSIS  1  0/101 (0.00%)  1/47 (2.13%) 
Nervous system disorders     
EPILEPSY  1  1/101 (0.99%)  0/47 (0.00%) 
Skin and subcutaneous tissue disorders     
ECZEMA  1  0/101 (0.00%)  1/47 (2.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
3-DAA/RBV TPV/RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   54/101 (53.47%)   43/47 (91.49%) 
Blood and lymphatic system disorders     
ANAEMIA  1  3/101 (2.97%)  14/47 (29.79%) 
LEUKOPENIA  1  0/101 (0.00%)  5/47 (10.64%) 
NEUTROPENIA  1  1/101 (0.99%)  12/47 (25.53%) 
THROMBOCYTOPENIA  1  0/101 (0.00%)  4/47 (8.51%) 
Gastrointestinal disorders     
ABDOMINAL PAIN  1  3/101 (2.97%)  4/47 (8.51%) 
ABDOMINAL PAIN UPPER  1  3/101 (2.97%)  4/47 (8.51%) 
ANAL PRURITUS  1  0/101 (0.00%)  12/47 (25.53%) 
APHTHOUS STOMATITIS  1  0/101 (0.00%)  3/47 (6.38%) 
HAEMORRHOIDS  1  0/101 (0.00%)  3/47 (6.38%) 
NAUSEA  1  10/101 (9.90%)  20/47 (42.55%) 
VOMITING  1  3/101 (2.97%)  7/47 (14.89%) 
General disorders     
ASTHENIA  1  8/101 (7.92%)  16/47 (34.04%) 
CHEST PAIN  1  0/101 (0.00%)  3/47 (6.38%) 
CHILLS  1  3/101 (2.97%)  5/47 (10.64%) 
FATIGUE  1  12/101 (11.88%)  12/47 (25.53%) 
GENERAL PHYSICAL HEALTH DETERIORATION  1  0/101 (0.00%)  3/47 (6.38%) 
INFLUENZA LIKE ILLNESS  1  0/101 (0.00%)  4/47 (8.51%) 
INJECTION SITE ERYTHEMA  1  0/101 (0.00%)  3/47 (6.38%) 
PYREXIA  1  2/101 (1.98%)  15/47 (31.91%) 
Infections and infestations     
GASTROENTERITIS  1  2/101 (1.98%)  3/47 (6.38%) 
NASOPHARYNGITIS  1  5/101 (4.95%)  5/47 (10.64%) 
Metabolism and nutrition disorders     
DECREASED APPETITE  1  3/101 (2.97%)  8/47 (17.02%) 
HYPERTRIGLYCERIDAEMIA  1  1/101 (0.99%)  3/47 (6.38%) 
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  3/101 (2.97%)  8/47 (17.02%) 
MUSCLE SPASMS  1  2/101 (1.98%)  3/47 (6.38%) 
MYALGIA  1  3/101 (2.97%)  9/47 (19.15%) 
Nervous system disorders     
DIZZINESS  1  5/101 (4.95%)  7/47 (14.89%) 
DYSGEUSIA  1  1/101 (0.99%)  4/47 (8.51%) 
HEADACHE  1  29/101 (28.71%)  21/47 (44.68%) 
LETHARGY  1  5/101 (4.95%)  3/47 (6.38%) 
PARAESTHESIA  1  0/101 (0.00%)  3/47 (6.38%) 
Psychiatric disorders     
DEPRESSED MOOD  1  0/101 (0.00%)  3/47 (6.38%) 
DEPRESSION  1  0/101 (0.00%)  3/47 (6.38%) 
INSOMNIA  1  6/101 (5.94%)  10/47 (21.28%) 
IRRITABILITY  1  2/101 (1.98%)  5/47 (10.64%) 
Respiratory, thoracic and mediastinal disorders     
COUGH  1  7/101 (6.93%)  12/47 (25.53%) 
OROPHARYNGEAL PAIN  1  1/101 (0.99%)  3/47 (6.38%) 
Skin and subcutaneous tissue disorders     
ALOPECIA  1  0/101 (0.00%)  6/47 (12.77%) 
DRY SKIN  1  0/101 (0.00%)  7/47 (14.89%) 
ECZEMA  1  0/101 (0.00%)  3/47 (6.38%) 
PRURITUS  1  13/101 (12.87%)  19/47 (40.43%) 
PRURITUS GENERALISED  1  0/101 (0.00%)  3/47 (6.38%) 
RASH  1  3/101 (2.97%)  12/47 (25.53%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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
ClinicalTrials.gov Identifier: NCT01854528    
Other Study ID Numbers: M13-862
2012-003738-18 ( EudraCT Number )
First Submitted: May 13, 2013
First Posted: May 15, 2013
Results First Submitted: November 24, 2015
Results First Posted: February 11, 2016
Last Update Posted: June 6, 2018