Study of AT-777 in Healthy Subjects and AT-777 in Combination With AT-527 in HCV-Infected Subjects

Study Overview
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Brief Summary
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This study has two parts. Part A will assess the safety, tolerability and pharmacokinetics (PK) of AT-777 in healthy subjects. Part B will assess the safety, antiviral activity/efficacy and PK of AT-777 in combination with AT-527 after 8 weeks of treatment in HCV-infected subjects.

Official Title
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A Phase I/IIa Study Assessing AT-777 in Healthy Subjects and AT-777 in Combination With AT-527 in HCV-Infected Subjects

Conditions
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Hepatitis C, Hepatitis C, Chronic, Chronic Hepatitis C, Hepatitis C Virus Infection, HCV Infection

Intervention / Treatment
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* Drug: AT-777
* Drug: Placebo
* Drug: AT-527


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All: Body mass index (BMI) of 18-35 kg/m2 Must agree to use protocol-specified methods of contraception Negative pregnancy test Willing to comply with the study requirements and to provide written informed consent Additional for Part A: -18-55 years of age Additional for Part B: 18-65 years of age HCV genotype 1, 2 or 3 Documented history compatible with chronic hepatitis C HCV RNA ≥ 10,000 IU/mL at Screening Exclusion Criteria: All: Pregnant or breastfeeding Abuse of alcohol or drugs Use of other investigational drugs within 30 days of dosing Other clinically significant medical conditions Additional for Part B: Prior exposure to any HCV NS5A inhibitor Cirrhosis Co-infection with hepatitis B virus or HIV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - 60 mg AT-777 single dose<br> | Drug: AT-777<br>* Administered orally as one or two 60 mg capsule(s) of AT-777 (inhibitor of HCV nonstructural protein 5A (NS5A)), depending on the arm.<br>|
| Experimental: Part A - 120 mg AT-777 single dose<br> | Drug: AT-777<br>* Administered orally as one or two 60 mg capsule(s) of AT-777 (inhibitor of HCV nonstructural protein 5A (NS5A)), depending on the arm.<br>|
| Placebo Comparator: Part A - Placebo single dose<br> | Drug: Placebo<br>* Administered orally, as one or two placebo capsules, depending on the arm.<br>|
| Experimental: Part B - 60 mg AT-777 + 550 mg AT-527 once daily for 8 weeks<br> | Drug: AT-777<br>* Administered orally as one or two 60 mg capsule(s) of AT-777 (inhibitor of HCV nonstructural protein 5A (NS5A)), depending on the arm.<br>Drug: AT-527<br>* Administered orally as one 550 mg tablet of AT-527 (nucleotide prodrug inhibitor of HCV nonstructural protein 5B (NS5B) polymerase), depending on the arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Number of subjects experiencing treatment-emergent adverse events | Through Day 6 for subjects in Part A | 
| Incidence of Treatment-Emergent Adverse Events | Number of subjects experiencing treatment-emergent adverse events | Through 4 weeks after end of treatment for subjects in Part B | 
| Antiviral Activity of AT-777 and AT-527 | Number of subjects who achieve plasma HCV RNA < lower limit of quantitation (LLOQ) and target not detected (TND) | Through 2 weeks of treatment for subjects in Part B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AT-777 maximum plasma concentration (Cmax) | PK | Day 1 for subjects in Part A | 
| AT-777 area under the concentration-time curve (AUC) | PK | Day 1 for subjects in Part A | 
| Proportion of subjects achieving sustained virologic response (SVR) | SVR defined as the HCV RNA < lower limit of quantitation (LLOQ) at 12 weeks after end of treatment | 12 weeks after end of treatment for subjects in Part B |