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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-003687-52 | EudraCT Number |
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The purpose of this study is to evaluate the safety and antiviral activity of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) with and without ribavirin (RBV) in patients with chronic hepatitis C virus genotype 1b (HCV GT1b) infection without cirrhosis.
A randomized, double-blind, multicenter study to evaluate the safety and antiviral activity of the combination of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 with and without ribavirin (RBV) in treatment-naïve, noncirrhotic participants with chronic hepatitis C virus genotype 1b (HCV GT1b) infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | Experimental | 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 and ABT-333, Plus Placebo RBV | Experimental | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABT-450/r/ABT-267, ABT-333 | Drug | Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate | 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, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN). | 12 weeks after last dose of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV | 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 endpoint was 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, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dan Cohen, MD | AbbVie | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24795200 | Background | Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, Tam E, Marinho RT, Tsai N, Nyberg A, Box TD, Younes Z, Enayati P, Green S, Baruch Y, Bhandari BR, Caruntu FA, Sepe T, Chulanov V, Janczewska E, Rizzardini G, Gervain J, Planas R, Moreno C, Hassanein T, Xie W, King M, Podsadecki T, Reddy KR; PEARL-III Study; PEARL-IV Study. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014 May 22;370(21):1983-92. doi: 10.1056/NEJMoa1402338. Epub 2014 May 4. | |
| 29377566 |
| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | ABT-450/r/ABT-267 and ABT-333, Plus RBV | 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 |
| FG001 | ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized participants who received at least 1 dose of study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | ABT-450/r/ABT-267 and ABT-333, Plus RBV | 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 |
| BG001 | ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analyses of Each Treatment Arm Compared to Historical Rate | 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, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN). | All randomized participants who received at least 1 dose of study drug (intent-to-treat [ITT] population); participants with missing data were counted as non-responders. | Posted | Number | percentage of participants | 12 weeks after last dose of study drug |
|
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 65 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ABT-450/r/ABT-267 and ABT-333, Plus RBV | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ATRIAL FIBRILLATION | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 16.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Information | AbbVie (prior sponsor, Abbott) | 800-633-9110 |
| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| C588260 | dasabuvir |
| C586094 | ombitasvir |
| C585405 | paritaprevir |
| C000607373 | Viekira Pak |
| D012254 | Ribavirin |
| ID | Term |
|---|---|
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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|
| Ribavirin | Drug | Capsule |
|
| Placebo for ribavirin | Drug | Capsule |
|
| 12 weeks after last dose of study drug |
| Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment | 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. | Baseline (Day 1) and Week 12 (End of Treatment) |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate | The percentage of participants with sustained virologic response (plasma HCV RNA 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, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV. | 12 weeks after last dose of study drug |
| Percentage of Participants With Virologic Failure During Treatment | 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). | Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12 |
| Percentage of Participants With Virologic Relapse After Treatment | Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (\ | Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-treatment) |
| Derived |
| Feld JJ, Bernstein DE, Younes Z, Vlierberghe HV, Larsen L, Tatsch F, Ferenci P. Ribavirin dose management in HCV patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin. Liver Int. 2018 Sep;38(9):1571-1575. doi: 10.1111/liv.13708. Epub 2018 Mar 14. |
ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 | ABT-450/r/ABT-267 and ABT-333, Plus RBV | 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 |
| OG001 | ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks |
|
|
|
| Secondary | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Noninferiority Analysis of ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV Compared With ABT-450/r/ABT-267 and ABT-333, Plus RBV | 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 endpoint was 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, plus placebo RBV compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV. | All randomized participants who received at least 1 dose of study drug (ITT population); participants with missing data were counted as non-responders. | Posted | Number | percentage of participants | 12 weeks after last dose of study drug |
|
|
|
|
| Secondary | Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment | 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. | All randomized participants who received at least 1 dose of study drug (ITT population) and had hemoglobin ≥ LLN reference range at baseline. | Posted | Number | percentage of participants | Baseline (Day 1) and Week 12 (End of Treatment) |
|
|
|
|
| Secondary | Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Superiority Analyses of Each Treatment Arm Compared to Historical Rate | The percentage of participants with sustained virologic response (plasma HCV RNA 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, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b treated with telaprevir and pegIFN/RBV. | All randomized participants who received at least 1 dose of study drug (ITT population); participants with missing data were counted as non-responders. | Posted | Number | percentage of particpants | 12 weeks after last dose of study drug |
|
|
|
|
| Secondary | Percentage of Participants With Virologic Failure During Treatment | 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). | All randomized participants who received at least 1 dose of study drug (ITT population). | Posted | Number | percentage of participants | Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12 |
|
|
|
| Secondary | Percentage of Participants With Virologic Relapse After Treatment | Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (\ | All randomized participants who received at least 1 dose of study drug (ITT population) with HCV RNA < LLOQ at the final treatment visit and completed treatment. | Posted | Number | percentage of participants | Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-treatment) |
|
|
|
| 4 |
| 210 |
| 133 |
| 210 |
| EG001 | ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks | 4 | 209 | 97 | 209 |
| CORONARY ARTERY DISEASE | Cardiac disorders | MedDRA 16.0 | Systematic Assessment |
|
| ARTHRITIS | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| INTRADUCTAL PROLIFERATIVE BREAST LESION | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.0 | Systematic Assessment |
|
| NEPHROLITHIASIS | Renal and urinary disorders | MedDRA 16.0 | Systematic Assessment |
|
| EPIDIDYMITIS | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
|
| UTERINE POLYP | Reproductive system and breast disorders | MedDRA 16.0 | Systematic Assessment |
|
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| DYSPEPSIA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| ASTHENIA | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| FATIGUE | General disorders | MedDRA 16.0 | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
|
| INSOMNIA | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
|
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 16.0 | Systematic Assessment |
|
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | MedDRA 16.0 | Systematic Assessment |
|
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.
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Noninferiority of the rate of sustained virologic response at 12 weeks after treatment for the ABT-450/r/ABT-267 and ABT-333, plus placebo RBV 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% CI for the difference in percentage of participants with sustained virologic response at 12 weeks after treatment must exceed -10.5% to achieve noninferiority. |
| Superiority or Other (legacy) |
| For the secondary efficacy endpoint of sustained virologic response at 12 weeks after treatment, based on a 2-sided significance level of 0.05 and an underlying rate of 92% or higher in each arm, a sample size of 200 participants per treatment arm provides >90% power to demonstrate superiority of each regimen to the historical rate for telaprevir plus pegIFN and RBV therapy (84%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority). | Percentage of Participants | 99.5 | 2-Sided | 95 | 98.6 | 100.0 | 95% CI 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 84% to achieve superiority. | Superiority or Other (legacy) |