Clinical trial NCT01200420: Multiple Ascending Dose Study of Miravirsen in Treatment-Naïve Chronic Hepatitis C Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Antisense
miR-122 antagonist
host factor
CHC
Lead sponsor: Santaris Pharma A/S
Sponsor class: INDUSTRY
First posted: 2010-09-13
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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.

Primary outcomes:
measure: Safety and tolerability
timeFrame: regularly over 18 weeks
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: continuously over 4 weeks
measure: Miravirsen treatment effect on viral titer
timeFrame: regularly over 18 weeks
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Frankfurt
country: Germany
facility: J.W. Goethe University Hospital
city: Amsterdam
country: Netherlands
facility: Academic Medical Center (AMC)
city: Rotterdam
country: Netherlands
facility: Erasmus MC University Hospital
city: Warszawa
country: Poland
facility: Klinika Hepatologii i Nabytych Niedoborow Immunologicznych WUM
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigation de Diego
city: Bratislava,
country: Slovakia
facility: FNsP Bratislava, Nemocnica akad.
Study officials:
affiliation: J.W. Goethe University Hospital, Frankfurt
name: Stefan Zeuzem, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.