Chronic Hepatitis C Virus, Hepatitis C, Chronic, Hepatitis C, Hepatic Cirrhosis, HCV
Conditions
Brief summary
This is an open-label trial to evaluate safety and efficacy of treatment with BEM + RZR in subjects with chronic HCV infection.
Interventions
DRUGBemnifosbuvir
550 mg administered orally once a day (QD) for 8 weeks
DRUGRuzasvir
180 mg administered orally once a day (QD) for 8 weeks
Sponsors
Atea Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent * Male or female subjects between ≥ 18 years of age (or the legal age of consent per local regulations) and ≤ 85 years of age * Female subjects of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or to the use of an acceptable effective contraception * Females must have a negative pregnancy test at Screening and at Day 1 prior to dosing * Subjects must be direct-acting antiviral (DAA)-treatment-naïve, defined as never exposed to an approved or experimental DAA for HCV * Documented medical history compatible with chronic HCV * Liver disease staging assessment as follows: * Absence of cirrhosis (F0 to F3) * Compensated cirrhosis (F4)
Exclusion criteria
* Female subject is pregnant or breastfeeding * Co-infected with hepatitis B virus (HBV; positive for hepatitis B surface antigen \[HBsAg\]) and/or human immunodeficiency virus (HIV) * Abuse of alcohol and/or illicit drug use that could interfere with adherence to study requirements as judged by the investigator * Prior exposure to any HCV DAA * Use of other investigational drugs within 30 days of dosing or plans to enroll in another clinical trial of an investigational agent while participating in the present study * Subject with known allergy to the study medications or any of their components * History or signs of decompensated liver disease: ascites, variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency * Cirrhotic and has a Child-Pugh score \>6, corresponding to a Child-Pugh Class B or C * History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC * Any other clinically significant medical condition that, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of the study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Sustained Virologic Response at 12 Weeks Post-treatment (SVR12) | Day 1 through 12 weeks after end of treatment | SVR12 defined as plasma hepatitis C virus (HCV) RNA less than the lower limit of quantitation (\<LLOQ) at 12 weeks post-treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Experiencing Virologic Failure | Day 1 through 12 weeks after end of treatment | Virologic failure defined as a confirmed 1 log10 increase in HCV RNA from post-baseline nadir, or confirmed increase in HCV RNA ≥ LLOQ in any subject who achieved HCV RNA \< LLOQ. |
| Percentage of Subjects Achieving Sustained Virologic Response at 24 Weeks Post-treatment (SVR24) | Day 1 through 24 weeks after end of treatment | SVR24 defined as plasma HCV RNA less than the lower limit of quantitation (\<LLOQ) at 24 weeks post-treatment |
Countries
Brazil, Canada, India, Mauritius, Moldova, Pakistan, Philippines, Romania, South Africa, South Korea, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BEM+RZR Bemnifosbuvir (BEM; AT-527) 550 mg in combination with Ruzasvir (RZR; AT-038) 180 mg. Administered orally as two BEM tablets and two RZR capsules once a day (QD) for 8 weeks. | 275 |
| Total | 275 |
Baseline characteristics
| Characteristic | BEM+RZR |
|---|---|
| Age, Continuous | 49.6 years STANDARD_DEVIATION 13.02 |
| Compensated Cirrhosis | 37 Participants |
| Genotype (GT) GT1 | 189 Participants |
| Genotype (GT) GT2 | 7 Participants |
| Genotype (GT) GT3 | 77 Participants |
| Genotype (GT) GT4 | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 55 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 192 Participants |
| Sex: Female, Male Female | 131 Participants |
| Sex: Female, Male Male | 144 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 275 |
| other Total, other adverse events | 64 / 275 |
| serious Total, serious adverse events | 19 / 275 |
Outcome results
Primary
Percentage of Subjects Achieving Sustained Virologic Response at 12 Weeks Post-treatment (SVR12)
SVR12 defined as plasma hepatitis C virus (HCV) RNA less than the lower limit of quantitation (\<LLOQ) at 12 weeks post-treatment
Time frame: Day 1 through 12 weeks after end of treatment
Population: The primary per-protocol analysis population included subjects who met all eligibility criteria, completed treatment (defined as being ≥90% compliant with the study drug regimen), had outcomes at post-treatment week 12, and had adequate study-drug exposure corroborated by pill counts and plasma drug levels adjudicated by an independent clinical pharmacologist.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM+RZR | Percentage of Subjects Achieving Sustained Virologic Response at 12 Weeks Post-treatment (SVR12) | 210 Participants |
Secondary
Percentage of Subjects Achieving Sustained Virologic Response at 24 Weeks Post-treatment (SVR24)
SVR24 defined as plasma HCV RNA less than the lower limit of quantitation (\<LLOQ) at 24 weeks post-treatment
Time frame: Day 1 through 24 weeks after end of treatment
Population: The primary per-protocol analysis population included subjects who met all eligibility criteria, completed treatment (defined as being ≥90% compliant with the study drug regimen), had outcomes at post-treatment week 12, and had adequate study-drug exposure corroborated by pill counts and plasma drug levels adjudicated by an independent clinical pharmacologist.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM+RZR | Percentage of Subjects Achieving Sustained Virologic Response at 24 Weeks Post-treatment (SVR24) | 206 Participants |
Secondary
Percentage of Subjects Experiencing Virologic Failure
Virologic failure defined as a confirmed 1 log10 increase in HCV RNA from post-baseline nadir, or confirmed increase in HCV RNA ≥ LLOQ in any subject who achieved HCV RNA \< LLOQ.
Time frame: Day 1 through 12 weeks after end of treatment
Population: The primary per-protocol analysis population included subjects who met all eligibility criteria, completed treatment (defined as being ≥90% compliant with the study drug regimen), had outcomes at post-treatment week 12, and had adequate study-drug exposure corroborated by pill counts and plasma drug levels adjudicated by an independent clinical pharmacologist.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BEM+RZR | Percentage of Subjects Experiencing Virologic Failure | 5 Participants |