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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Santaris Pharma A/S
ClinicalTrials.gov Identifier:
NCT01200420
First received: September 9, 2010
Last updated: January 26, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: miravirsen
Drug: saline
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Santaris Pharma A/S:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: regularly over 18 weeks ] [ Designated as safety issue: Yes ]
    Safety evaluation will study the adverse event (AE) profile, clinical laboratory safety tests, vital signs, 12 lead and ECG monitoring.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: continuously over 4 weeks ] [ Designated as safety issue: No ]
    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.

  • Miravirsen treatment effect on viral titer [ Time Frame: regularly over 18 weeks ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: September 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: miravirsen
Dose escalation study with review of safety data following each cohort.
Drug: miravirsen
SC injection
Other Name: SPC3649
Placebo Comparator: saline
Dose escalation study with review of safety data following each cohort.
Drug: saline
SC injection

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200420

Locations
United States, Texas
Alamo Medical Research
San Antonio, Texas, United States
Germany
J.W. Goethe University Hospital
Frankfurt, Germany, D-60590
Netherlands
Academic Medical Center (AMC)
Amsterdam, Netherlands, 22660 1100 D
Erasmus MC University Hospital
Rotterdam, Netherlands, 3015 CE
Poland
Klinika Hepatologii i Nabytych Niedoborow Immunologicznych WUM
Warszawa, Poland, 01-201
Puerto Rico
Fundacion de Investigation de Diego
San Juan, Puerto Rico
Slovakia
FNsP Bratislava, Nemocnica akad.
Bratislava,, Slovakia, 833 05
Sponsors and Collaborators
Santaris Pharma A/S
Investigators
Principal Investigator: Stefan Zeuzem, MD J.W. Goethe University Hospital, Frankfurt
  More Information

No publications provided by Santaris Pharma A/S

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Santaris Pharma A/S
ClinicalTrials.gov Identifier: NCT01200420     History of Changes
Other Study ID Numbers: SPC3649-203, 2010-019057-17
Study First Received: September 9, 2010
Last Updated: January 26, 2012
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Slovakia: State Institute for Drug Control

Keywords provided by Santaris Pharma A/S:
Antisense
miR-122 antagonist
host factor
CHC

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on July 20, 2014