Hepatitis C, Chronic
Conditions
Keywords
Chronic Hepatitis C, Genotype 1, Hepatitis C, Liver Diseases, Hepatitis, Ribavirin, Antiviral Agents, Anti-infective Agents, Protease Inhibitors, NS5a Inhibitors, Viral
Brief summary
The purpose of this study was to evaluate the safety, tolerability, and efficacy of 12 weeks of treatment with sovaprevir, ACH-0143102, and ribavirin (RBV) in genotype-1 (GT-1), treatment-naive, hepatitis C virus (HCV) participants.
Interventions
DRUGSovaprevir
Nonstructural protein 3/4A protease inhibitor.
DRUGACH-3102
Nonstructural protein 5A inhibitor.
DRUGRibavirin
DRUGPlacebo
Sponsors
Achillion, a wholly owned subsidiary of Alexion
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chronic HCV infection. * HCV GT-1. * HCV ribonucleic acid \> 10,000 international units/milliliter at screening. * Female participants must be willing to use 2 effective methods of contraception, one of which must be a barrier method, during the dosing period and 6 months after the last dose of RBV. Females of childbearing potential must have a negative pregnancy test at screening and baseline. * Male participants must be willing to use an effective barrier method of contraception throughout the dosing period and for 6 months. * Signed and dated written informed consent form. * Willing to participate in all study activities and all study requirements (including effective contraception) during the study period. * Treatment-naïve participants were defined as those participants who have never received pegylated interferon, RBV, or a direct-acting anti-viral agent for the treatment of chronic HCV infection. * A liver biopsy within the last 3 years without evidence of cirrhosis.
Exclusion criteria
* Body mass index \> 36.0 kilograms/meter squared. * Pregnant or nursing (lactating) female participants confirmed by a positive human chorionic gonadotropin laboratory test or contemplating pregnancy. * Participation in any interventional clinical trial within 35 days prior to first study medication dose administration on Day 1. * Known human immunodeficiency virus (HIV)-1 or HIV-2 infection/serology and/or positive hepatitis B surface antigen. * Use of dietary supplements, grapefruit juice, herbal supplements, cytochrome P450 (CYP) 2C8 substrates, CYP3A4 inducers and inhibitors, P-glycoprotein inducers and substrates, organic-anion-transporting polypeptide inhibitors and substrates, and potent inducers of other CYP enzymes within 14 days prior to dosing through 7 days following completion of study medications. * Clinically significant laboratory abnormality at screening (specified in protocol). * Other forms of liver disease. * History of severe or uncontrolled psychiatric disease. * History of malignancy of any organ system, treated or untreated within the past 5 years. * History of major organ transplantation. * Use of bone marrow colony stimulating factor agents within 3 months prior to baseline. * History of seizure disorder requiring ongoing medical therapy. * History of known coagulopathy including hemophilia. * History of hemoglobinopathy, including sickle cell anemia and thalassemia. * History of immunologically mediated disease (specified in protocol). * History of clinical evidence of significant chronic cardiac disease ( specified in protocol). * Electrocardiogram with any clinically significant abnormality. * Structural or functional cardiac abnormalities (specified in protocol). * History of chronic obstructive pulmonary disease, emphysema, or other chronic lung disease. * Participants currently abusing amphetamines, cocaine or opiates, or with ongoing alcohol abuse in the judgement of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Of Sustained Virologic Response 4 Weeks (SVR4) After The Completion Of Treatment | Four weeks after the completion of treatment | Incidence of SVR4 after the completion of dosing, reported as hepatitis C virus (HCV) ribonucleic acid less than the lower limit of quantification, in participants who received active treatment (sovaprevir and ACH-0143102 in combination with RBV) as compared to those who received placebo. |
| Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | 12 weeks | To determine the safety and tolerability of 12 weeks of sovaprevir/ACH-0143102/RBV treatment in participants with chronic genotype-1 (GT-1) HCV, the following criteria will be used: the number of participants with discontinuations due to adverse events (AEs), treatment-emergent Grade 3/Grade 4 (G3/G4) AEs, treatment-emergent G3/G4 laboratory abnormalities, and clinically significant electrocardiograms (ECGs). |
Participant flow
Recruitment details
Participants were recruited from 7 sites in the United States and 1 site in Canada between 07 May 2013 and 04 April 2014.
Pre-assignment details
Participants were screened within 4 weeks (-28 to -1 days) before administration of the study drug. Participants who meet all eligibility criteria were instructed to arrive at the study center on baseline day.
Participants by arm
| Arm | Count |
|---|---|
| Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg Sovaprevir 200 mg qd + ACH-3102 150 mg loading dose on Day 1, followed by 50 mg qd + RBV weight-based 1000-1200 mg qd for 12 weeks. | 10 |
| Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg Sovaprevir 400 mg qd + ACH-3102 150 mg loading dose on Day 1, followed by 50 mg qd + RBV weight-based 1000-1200 mg qd for 12 weeks. | 10 |
| Placebo Placebo for sovaprevir capsule qd + placebo for ACH-3102 150 mg loading dose on Day 1 followed, by placebo for 50 mg qd + placebo for weight-based RBV qd for 12 weeks. | 10 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Non-compliance with Study Drug | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 29 Participants | 10 Participants | 9 Participants |
| Age, Continuous | 53.8 Years STANDARD_DEVIATION 8.58 | 51.7 Years STANDARD_DEVIATION 9.4 | 50.7 Years STANDARD_DEVIATION 8.51 | 50.5 Years STANDARD_DEVIATION 11.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 26 Participants | 9 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 175.6 Centimeters STANDARD_DEVIATION 7.53 | 171.8 Centimeters STANDARD_DEVIATION 9.66 | 169.7 Centimeters STANDARD_DEVIATION 9.76 | 170.1 Centimeters STANDARD_DEVIATION 11.14 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 22 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 18 Participants | 6 Participants | 6 Participants |
| Weight | 81.5 Kilograms STANDARD_DEVIATION 11.9 | 80.2 Kilograms STANDARD_DEVIATION 12.1 | 81.5 Kilograms STANDARD_DEVIATION 9.88 | 78.1 Kilograms STANDARD_DEVIATION 15.02 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 | 1 / 10 | 0 / 10 |
Outcome results
Primary
Incidence Of Sustained Virologic Response 4 Weeks (SVR4) After The Completion Of Treatment
Incidence of SVR4 after the completion of dosing, reported as hepatitis C virus (HCV) ribonucleic acid less than the lower limit of quantification, in participants who received active treatment (sovaprevir and ACH-0143102 in combination with RBV) as compared to those who received placebo.
Time frame: Four weeks after the completion of treatment
Population: The analysis population for SVR4 was the full analysis (FA) set, defined as all randomized participants who received at least 1 dose of the study drug and had at least 1 baseline/post HCV RNA assessment. For this study, the FA set and the safety population were the same.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Incidence Of Sustained Virologic Response 4 Weeks (SVR4) After The Completion Of Treatment | 50 Percentage of participants with SVR4 |
| Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Incidence Of Sustained Virologic Response 4 Weeks (SVR4) After The Completion Of Treatment | 70 Percentage of participants with SVR4 |
| Placebo | Incidence Of Sustained Virologic Response 4 Weeks (SVR4) After The Completion Of Treatment | 0 Percentage of participants with SVR4 |
Comparison: Differences in proportions between Group 1 (sovaprevir 200 mg plus ACH-3102 150/50 mg plus RBV) and overall placebo (placebo from Group 1 and Group 2 combined) along with corresponding 95% confidence intervals for risk difference calculated using exact unconditional methods were obtained.95% CI: [1.8, 82.7]
Comparison: Differences in proportions between Group 2 (sovaprevir 400 mg plus ACH-3102 150/50 mg plus RBV) and overall placebo (placebo from Group 1 and Group 2 combined) along with corresponding 95% confidence intervals for risk difference calculated using exact unconditional methods were obtained.95% CI: [24.2, 93.6]
Primary
Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants
To determine the safety and tolerability of 12 weeks of sovaprevir/ACH-0143102/RBV treatment in participants with chronic genotype-1 (GT-1) HCV, the following criteria will be used: the number of participants with discontinuations due to adverse events (AEs), treatment-emergent Grade 3/Grade 4 (G3/G4) AEs, treatment-emergent G3/G4 laboratory abnormalities, and clinically significant electrocardiograms (ECGs).
Time frame: 12 weeks
Population: The analysis population for safety and tolerability was the safety population, defined as all randomized participants who received at least 1 dose of study drug. For this study, the safety population and the FA set were the same.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Discontinuations due to AEs | 0 participants |
| Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Treatment Emergent G3/G4 AEs | 0 participants |
| Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Treatment Emergent G3/G4 Abnormalities | 3 participants |
| Sovaprevir 200 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Clinically Significant ECGs | 0 participants |
| Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Clinically Significant ECGs | 0 participants |
| Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Discontinuations due to AEs | 0 participants |
| Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Treatment Emergent G3/G4 Abnormalities | 2 participants |
| Sovaprevir 400 mg, ACH-3102 150/50 mg, RBV 1000-1200 mg | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Treatment Emergent G3/G4 AEs | 0 participants |
| Placebo | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Clinically Significant ECGs | 0 participants |
| Placebo | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Treatment Emergent G3/G4 AEs | 0 participants |
| Placebo | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Treatment Emergent G3/G4 Abnormalities | 0 participants |
| Placebo | Safety And Tolerability Of 12 Weeks Of Sovaprevir And ACH-3102 In Combination With RBV In GT-1 HCV Participants | Discontinuations due to AEs | 0 participants |