Phase 2, Multiple Ascending Dose Proof of Concept Study

Study Overview
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Brief Summary
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This is a phase 2a study to evaluate the safety and tolerability of multiple oral doses of CMX157 at increasing dose levels.

Detailed Description
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This is a phase 2a study to evaluate the safety and tolerability of multiple oral doses of CMX157 at increasing dose levels in hepatitis B virus(HBV) infected subjects.

Official Title
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A Phase 2, Randomized, Open-label, Ascending, Sequential Dose Group, Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of CMX157 in HBV-infected Subjects

Conditions
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Infectious Disease

Intervention / Treatment
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* Drug: CMX157
* Drug: TDF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving written informed consent. Capable of completing study requirements. Chronic hepatitis B positive. HBV treatment naïve. Exclusion Criteria: Positive result for HCV(hepatitis C virus), HDV(hepatitis D virus) or HIV(human immunodeficiency virus). History or medical condition that could impact patient safety. Current or past abuse of alcohol or illicit drugs. Abnormal laboratory value or ECG. Pregnant or breastfeeding. Clinical, histologic or laboratory evidence of significant liver fibrosis or cirrhosis. Systemic immunosuppression. Received an investigational drug or investigational vaccine within the 90 days prior to the first dose of study drug.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CMX157 5mg versus TDF<br>CMX157, 5mg tablet, 28 days versus TDF(tenofovir disoproxil fumerate) 300mg tablet, 28 days | Drug: CMX157<br>* tablet<br>* Other names: lipid conjugate TFV(tenofovir);Drug: TDF<br>* 300mg tablet<br>* Other names: tenofovir disoproxil fumerate;|
| Active Comparator: CMX157 10mg versus TDF<br>CMX157, 10mg tablet, 28 days versus TDF 300mg tablet, 28 days | Drug: CMX157<br>* tablet<br>* Other names: lipid conjugate TFV(tenofovir);Drug: TDF<br>* 300mg tablet<br>* Other names: tenofovir disoproxil fumerate;|
| Active Comparator: CMX157 25mg versus TDF<br>CMX157, 25mg tablet, 28 days versus TDF 300mg tablet, 28 days | Drug: CMX157<br>* tablet<br>* Other names: lipid conjugate TFV(tenofovir);Drug: TDF<br>* 300mg tablet<br>* Other names: tenofovir disoproxil fumerate;|
| Active Comparator: CMX157 50mg versus TDF<br>CMX157, 50mg tablet, 28 days versus TDF 300mg tablet, 28 days | Drug: CMX157<br>* tablet<br>* Other names: lipid conjugate TFV(tenofovir);Drug: TDF<br>* 300mg tablet<br>* Other names: tenofovir disoproxil fumerate;|
| Active Comparator: CMX157 100mg versus TDF<br>CMX157, 100mg tablet, 28 days versus TDF 300mg tablet, 28 days | Drug: CMX157<br>* tablet<br>* Other names: lipid conjugate TFV(tenofovir);Drug: TDF<br>* 300mg tablet<br>* Other names: tenofovir disoproxil fumerate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the safety and tolerability of increasing multiple oral doses of CMX157 in HBV + patients | Capture adverse events, physical examinations, ECGs and clinical laboratory panels | 28 days | 
| To evaluate the antiviral activity of CMX157 versus tenofovir disproxil fumarate(TDF). | HBV DNA levels | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects, Cmax. | Measuring Cmax(concentration maximum): the peak plasma concentration. | 28 days | 
| Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects: Tmax. | Measuring Tmax(time maximum): the time Cmax was observed. | 28 days | 
| Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects: AUC. | Measuring AUC(area under the curve): area under plasma concentration versus time curve. | 28 days | 
| Evaluation of the pharmacokinetics of multiple doses of oral CMX157 in HBV + subjects: Cmin. | Measuring Cmin(concentration minimum): minimum observed plasma concentration. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis B(CHB)