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-NaÃ¯ve Subjects with Chronic Hepatitis C (CHC) Infectio

Phase 2

Completed

Conditions: Hepatitis C
liver inflammation
10047438

Registration Number: NL-OMON34513

Lead Sponsor: Santaris Pharma A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 16

Inclusion Criteria

1. Male or female, age 18 to 65 years, inclusive
2. BMI 18-38 kg/m2
3. Treatment-naïve to interferon-alpha based therapies
4. HCV genotype 1
5. Clinical and laboratory findings consistent with a clinical diagnosis of Chronic Hepatitis C (CHC), including:
a. Previous documentation of positive HCV serology (HCV antibody or HCV RNA) at least 24 weeks prior to enrollment,
OR
b. 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
6. Serum HCV RNA > 75,000 IU/mL at Screening
7. Screening hematology, clinical chemistries, coagulation and urinalysis are not clinically significant and the following criteria are met:
a. Platelets >100,000/mm3
b. Total WBC > 3000/mm3 and ANC >1500/mm3
c. Hemoglobin > 11 g/dL for females and > 12 g/dL for males
d. Total and direct bilirubin, WNL (except for clearly documented Gilbert*s Syndrome)
e. ALT < 3 x ULN
f. Serum creatinine WNL and estimated creatinine clearance rate as calculated by the Cockcroft-Gault formula > 80 ml/min
8. 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.
9. 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.
• For female study participants, adequate birth control methods will be defined as: intrauterine device or double barrier contraception, i.e., condom plus diaphragm, condom or diaphragm plus spermicidal gel /foam.
• For males study participants, adequate birth control methods will be defined as: double barrier contraception, i.e., condom plus diaphragm; condom or diaphragm plus spermicidal gel/foam. ;Note: Females who are not of childbearing potential must meet one of the following criteria:
• Post-menopause - defined as one year without menses or follicle-stimulating hormone (FSH) of >40 U/mL
• Surgical menopause - hysterectomy, bilateral oophorectomy, or bilateral tubal ligation.

Exclusion Criteria

Subjects who meet any of the following criteria at Screening are not eligible to participate in this study:
1. Other known cause of liver disease except for CHC
2. 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
3. History of hepatocellular carcinoma (HCC) on imaging studies or serum alpha-fetoprotein (AFP) > 50 ng/mL at Screening
4. Concurrent clinically significant medical diagnosis (other than hepatitis C-related conditions) that would potentially interfere with the subjects study compliance or confound study results
5. Concurrent social conditions (e.g. drugs, alcohol, transportation) which would potentially interfere with the subject*s study compliance
6. Clinically significant illness within 30 days preceding entry into the study
7. Participated in an investigational drug study within 30 days or 5 half-lives, whichever is longer, prior to the start of study medication.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety and tolerability will be assessed by routine clinical laboratory<br /><br>assessments, physical examinations, viral signs, electrocardiograms, and<br /><br>adverse events.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Pharmacokinetics will be assessed by the following parameters:<br /><br>Cmax, the maximum observed plasma concentration;<br /><br>tmax, the time for occurrence of Cmax;<br /><br>AUC0-t, the area under the plasma concentration versus time curve from time<br /><br>zero to the last sampling time (24 hours), and it will be calculated using the<br /><br>linear trapetzoidal rule;<br /><br>Cl/F, the total body clearance calculated as Dose/AUC, where F is the<br /><br>bioavailability;<br /><br>V/F, the apparent volume of distribution approximated to Dose/Cmax; and<br /><br>t*, the half-life will be estimated from the drug concentration at 2 hours (C2)<br /><br>and trough concentration (Ct, after 168 hours; i.e. prior to the next coming<br /><br>dose)<br /><br>Pharmacodynamics will be assessed by measurement of circulating HCV RNA,<br /><br>miR-122 and IP-10 in plasma. </p><br>