Main objectiveTo determine the safety and tolerability of multiple dosing of miravirsen in subjects infected with CHC.Secondary objectivesTo assess the pharmacokinetics (PK) of multiple dosing of miravirsen administered subcutaneously to subjects…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety and tolerability will be assessed by routine clinical laboratory
assessments, physical examinations, viral signs, electrocardiograms, and
adverse events.
Secondary outcome
Pharmacokinetics will be assessed by the following parameters:
Cmax, the maximum observed plasma concentration;
tmax, the time for occurrence of Cmax;
AUC0-t, the area under the plasma concentration versus time curve from time
zero to the last sampling time (24 hours), and it will be calculated using the
linear trapetzoidal rule;
Cl/F, the total body clearance calculated as Dose/AUC, where F is the
bioavailability;
V/F, the apparent volume of distribution approximated to Dose/Cmax; and
t*, the half-life will be estimated from the drug concentration at 2 hours (C2)
and trough concentration (Ct, after 168 hours; i.e. prior to the next coming
dose)
Pharmacodynamics will be assessed by measurement of circulating HCV RNA,
miR-122 and IP-10 in plasma.
Background summary
Miravirsen (SPC3649) is a locked nucleic acid modified phosphorothioate
oligonucleotide that targets microRNA-122 (miR-122), a necessary cofactor for
HCV accumulation in plasma. Miravirsen is indicated as a possible new
treatment of Chronic Hepatitis C (CHC).
Study objective
Main objective
To determine the safety and tolerability of multiple dosing of miravirsen in
subjects infected with CHC.
Secondary objectives
To assess the pharmacokinetics (PK) of multiple dosing of miravirsen
administered subcutaneously to subjects with CHC.
To assess the effect of miravirsen on viral titer in subjects with CHC.
To assess the effect of miravirsen on circulating miR-122 and IP-10 levels in
subjects with CHC.
Study design
This is a randomized, double-blind, placebo-controlled, sequential cohort,
ascending multiple-dose study to assess safety, tolerability, pharmacokinetics
and antiviral activity of miravirsen in subjects with CHC (genotype 1).
Sequential cohorts of subjects will be randomized to miravirsen or placebo (9
active: 3 placebo). Miravirsen will be administered as subcutaneous (SC)
injections at doses of 3, 5, or 7 mg/kg given weekly for 29 days (5 doses), or
10 mg/kg every other week for 3 total doses. Placebo SC injections will be an
equivalent volume of 0.9% saline. Subjects will return for follow-up visits for
an overall study duration of 18 weeks.
Intervention
Not applicable
Study burden and risks
Miravirsen may cause the following side effects: a decrease in cholesterol, an
uncommon and minor elevation in liver enzymes (AST, ALT), and rare injection
site reactions involving short-lived skin discoloration.
The risks of drawing blood during the study include temporary discomfort from
the needle with possible bruising and swelling at the needle site and, in rare
circumstances infection.
It is not expected that participation in this study will provide any benefit
to subjects infected with CHC.
Kogle Allé 6
DK-2970
DK
Kogle Allé 6
DK-2970
DK
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-019057-17-NL |
| CCMO | NL32116.000.10 |