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

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01200420
• Other study ID #: SPC3649-203
• Secondary ID: 2010-019057-17
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2010
• Last updated: January 26, 2012
• Start date: September 2010
• Est. completion date: December 2011

Study information

• Verified date: January 2012
• Source: Santaris Pharma A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Slovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• miravirsen
SC injection
• saline
SC injection

Locations

Country	Name	City	State
Germany	J.W. Goethe University Hospital	Frankfurt
Netherlands	Academic Medical Center (AMC)	Amsterdam
Netherlands	Erasmus MC University Hospital	Rotterdam
Poland	Klinika Hepatologii i Nabytych Niedoborow Immunologicznych WUM	Warszawa
Puerto Rico	Fundacion de Investigation de Diego	San Juan
Slovakia	FNsP Bratislava, Nemocnica akad.	Bratislava,
United States	Alamo Medical Research	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Santaris Pharma A/S

Countries where clinical trial is conducted

United States,  Germany,  Netherlands,  Poland,  Puerto Rico,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	Miravirsen treatment effect on viral titer		regularly over 18 weeks	No