Multiple Ascending Dose Study of Miravirsen in Treatment-Naïve Chronic Hepatitis C Subjects

Study Overview
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Brief Summary
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The main purpose of this study is to determine the safety and tolerability of multiple dosing of miravirsen in subjects infected with chronic hepatitis C. Secondary purpose includes assessment of pharmacokinetics of miravirsen and assessment of miravirsen's effect on HCV viral titer.

Official Title
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A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Assess Safety, Tolerability, Pharmacokinetics and Antiviral Activity of SPC3649 (Miravirsen) Administered to Treatment-Naïve Subjects With Chronic Hepatitis C (CHC) Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: miravirsen
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 18-38 kg/m2 Treatment-naïve to interferon-alpha based therapies HCV genotype 1 Clinical and laboratory findings consistent with a clinical diagnosis of CHC, including: Previous documentation of positive HCV serology (HCV antibody or HCV RNA) at least 24 weeks prior to enrollment, OR Positive HCV serology (HCV antibody or HCV RNA) with a prior remote risk factor (more than 24 weeks prior to Screening) for the acquisition of hepatitis C Serum HCV RNA > 75,000 IU/mL at Screening (North American sites only). Liver biopsy within 36 months of Day 1, indicating the absence of cirrhosis Screening hematology, clinical chemistries, coagulation and urinalysis are not clinically significant and the following criteria are met: Platelets >100,000/mm3 Total WBC > 3000/mm3 and ANC >1500/mm3 Hemoglobin > 11 g/dL for females and > 12 g/dL for males Total and direct bilirubin, WNL (except for clearly documented Gilbert's Syndrome) ALT < 5 x ULN Serum creatinine WNL and creatinine clearance as calculated by the Cockcroft-Gault formula > 80 ml/min Negative results on the following Screening laboratory tests: urine or serum pregnancy test (for women of childbearing potential), hepatitis B surface antigen and human immunodeficiency virus (HIV) antibody. For men and women of childbearing potential, willingness to utilize adequate contraception and not become pregnant (or have their partner become pregnant) during the full course of the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to Screening). IUD, Depo-Provera, Norplant System implants, bilateral tubal ligation, vasectomy, condom or diaphragm plus either contraceptive sponge, foam or jelly and abstinence. Exclusion Criteria: Other known cause of liver disease except for CHC History or symptoms of decompensated liver disease: Child-Pugh Class B or C, including ascites, hepatic encephalopathy, esophageal variceal bleeding, fibrosis or other signs of hepatic insufficiency or portal hypertension History of hepatocellular carcinoma (HCC) on imaging studies or serum alpha-fetoprotein (AFP) > 50 ng/mL at Screening Concurrent clinically significant medical diagnosis (other than hepatitis C-related conditions) that would potentially interfere with the subjects study compliance or confound study results Concurrent social conditions (e.g. drugs, alcohol, transportation) which would potentially interfere with the subject's study compliance Clinically significant illness within 30 days preceding entry into the study Participated in an investigational drug study within 30 days or 5 half-lives, whichever is longer, prior to the start of study medication.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: miravirsen<br>Dose escalation study with review of safety data following each cohort. | Drug: miravirsen<br>* SC injection<br>* Other names: SPC3649;|
| Placebo Comparator: saline<br>Dose escalation study with review of safety data following each cohort. | Drug: saline<br>* SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Safety evaluation will study the adverse event (AE) profile, clinical laboratory safety tests, vital signs, 12 lead and ECG monitoring. | regularly over 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Appropriate PK parameters, e.g. maximum observed plasma drug concentrations, area under the plasma concentration-time curves, the apparent terminal rate constant and corresponding half-life for miravirsen. | continuously over 4 weeks | 
| Miravirsen treatment effect on viral titer |  | regularly over 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antisense, miR-122 antagonist, host factor, CHC