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

NCT ID: NCT01200420

Last Updated: 2012-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-30

Study Completion Date

2011-12-31

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.

Detailed Description

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Conditions

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Hepatitis C

Keywords

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Antisense miR-122 antagonist host factor CHC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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miravirsen

Dose escalation study with review of safety data following each cohort.

Group Type EXPERIMENTAL

miravirsen

Intervention Type DRUG

SC injection

saline

Dose escalation study with review of safety data following each cohort.

Group Type PLACEBO_COMPARATOR

saline

Intervention Type DRUG

SC injection

Interventions

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miravirsen

SC injection

Intervention Type DRUG

saline

SC injection

Intervention Type DRUG

Other Intervention Names

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SPC3649

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Santaris Pharma A/S

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stefan Zeuzem, MD

Role: PRINCIPAL_INVESTIGATOR

J.W. Goethe University Hospital, Frankfurt

Locations

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Alamo Medical Research

San Antonio, Texas, United States

Site Status

J.W. Goethe University Hospital

Frankfurt, , Germany

Site Status

Academic Medical Center (AMC)

Amsterdam, , Netherlands

Site Status

Erasmus MC University Hospital

Rotterdam, , Netherlands

Site Status

Klinika Hepatologii i Nabytych Niedoborow Immunologicznych WUM

Warsaw, , Poland

Site Status

Fundacion de Investigation de Diego

San Juan, , Puerto Rico

Site Status

FNsP Bratislava, Nemocnica akad.

Bratislava, , Slovakia

Site Status

Countries

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Romania United States Germany Netherlands Poland Puerto Rico Slovakia

References

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Ottosen S, Parsley TB, Yang L, Zeh K, van Doorn LJ, van der Veer E, Raney AK, Hodges MR, Patick AK. In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122. Antimicrob Agents Chemother. 2015 Jan;59(1):599-608. doi: 10.1128/AAC.04220-14. Epub 2014 Nov 10.

Reference Type DERIVED
PMID: 25385103 (View on PubMed)

Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013 May 2;368(18):1685-94. doi: 10.1056/NEJMoa1209026. Epub 2013 Mar 27.

Reference Type DERIVED
PMID: 23534542 (View on PubMed)

Other Identifiers

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2010-019057-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SPC3649-203

Identifier Type: -

Identifier Source: org_study_id