Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00229749
Status:
TERMINATED
Last Update Posted:
2008-04-10
First Post:
2005-09-28
Brief Title:
Study of AVI-4065 in Healthy Volunteers and Chronic Active HCV Patients
Sponsor:
Sarepta Therapeutics Inc
Organization:
Sarepta Therapeutics Inc
Study Overview
Official Title:
Exploratory Study of AVI-4065 Injection to Design Therapeutic Dosing for Chronic Active HCV Patients
Status:
TERMINATED
Status Verified Date:
2008-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Limited viral load reduction in HCV subjects
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Chronic active hepatitis C viral infections are difficult to treat current drug therapies can result in severe side effects that some patients will not tolerate AVI-4065 Injection is a new drug designed to prevent the virus from reproducing in the body We tested this drug in healthy adult volunteers to optimize the dosing regimen and are now proceeding in adult patients with chronic active hepatitis C infections Patients who have the disease and who have had treatment but without success will be recruited for the study
The treatment of HCV patients initially consisted of subcutaneous injections given twice a day for 14-days Treatment arms of 28 days twice or three-times per day have been added
The treatment of HCV patients initially consisted of subcutaneous injections given twice a day for 14-days Treatment arms of 28 days twice or three-times per day have been added
Detailed Description:
Hepatitis C virus HCV is the most common blood-borne infection in the United States and a worldwide public health problem of epidemic proportions Benign in the acute phase of infection HCV infection usually becomes chronic in 70 of those originally infected Chronic HCV infection leads to inflammation of the liver hepatitis cirrhosis end-stage liver disease and hepatocellular carcinoma In the United States alone there are over 27 million individuals with chronic HCV hepatitis Standard treatment of chronic HCV hepatitis is combination therapy for 24 to 48 weeks with alpha interferon and ribavirin This combination has limited efficacy poor tolerability and significant expense in terms of drug and ancillary laboratory testing It is well recognized that new treatment options are needed which are more efficacious potent less toxic and less expensive
AVI BioPharma has pursued discovery of a drug against HCV using proprietary Neugene or Phosphorodiamidate Morpholino Oligomer PMO synthetic chemistry Neugene PMO compounds as a drug class are considered safe in humans and do not activate complement alter clotting times or bind to α-adrenergic receptors which can produce hypotension like the phosphorothioate antisense compounds One PMO AVI-4065 has been identified as likely to inhibit all 5 genotypes of HCV based on in vitro and in vivo animal models There are specific data that confirm that AVI-4065 can inhibit HCV RNA dependent PNA polymerase RdRp encoded in NS5 and the HCV protease NS3 in a non-competitive inhibitory fashion The 50 percent Effective Concentration EC50 is 308 nM and the efficacy is nearly 100 at 3 μM These data suggest that AVI-4065 is capable of inhibiting HCV protein translation in a robust manner at concentrations that should be achievable in patients In rigorous GLP safety pharmacology and toxicity models in a variety of animal species at dosage levels up to 5 times the maximum anticipated human dosage level inclusive of non-human primates AVI-4065 was considered safe well tolerated and without dose-limiting toxicities Additionally AVI-4065 Injection was safe and well-tolerated in the three dose-escalating groups of 31 healthy volunteers Part I with no serious adverse events Adverse events that did occur were few self-limited and mild to moderate and did not require intervention this observation held true for the first HCV patients receiving AVI-4065 Injection
AVI BioPharmas first human use of AVI-4065 Injection involved an open-label multi-center exploratory dose escalating design in healthy adult volunteers The objective of this part of the study was to assess safety tolerability and to design a potentially therapeutic dosage regimen The objective of the second part of the study is to evaluate safety tolerability pharmacokinetics pharmacodynamics and signals of HCV virus response in cohorts of HCV patient volunteers that are interferon and ribavirin treatment failures
The ability of the drug to effect baseline HCV RNA levels over the study duration will be evaluated using a conventional PCR-based assay If there are promising results from this phase of the clinical trial viz a 2 log decrease in HCV RNA levels from baseline within study surveillance it will provide the rational basis for additional clinical testing of AVI-4065 Injection among HCV patients that are treatment refractory viz relapsers and non-responders
AVI BioPharma has pursued discovery of a drug against HCV using proprietary Neugene or Phosphorodiamidate Morpholino Oligomer PMO synthetic chemistry Neugene PMO compounds as a drug class are considered safe in humans and do not activate complement alter clotting times or bind to α-adrenergic receptors which can produce hypotension like the phosphorothioate antisense compounds One PMO AVI-4065 has been identified as likely to inhibit all 5 genotypes of HCV based on in vitro and in vivo animal models There are specific data that confirm that AVI-4065 can inhibit HCV RNA dependent PNA polymerase RdRp encoded in NS5 and the HCV protease NS3 in a non-competitive inhibitory fashion The 50 percent Effective Concentration EC50 is 308 nM and the efficacy is nearly 100 at 3 μM These data suggest that AVI-4065 is capable of inhibiting HCV protein translation in a robust manner at concentrations that should be achievable in patients In rigorous GLP safety pharmacology and toxicity models in a variety of animal species at dosage levels up to 5 times the maximum anticipated human dosage level inclusive of non-human primates AVI-4065 was considered safe well tolerated and without dose-limiting toxicities Additionally AVI-4065 Injection was safe and well-tolerated in the three dose-escalating groups of 31 healthy volunteers Part I with no serious adverse events Adverse events that did occur were few self-limited and mild to moderate and did not require intervention this observation held true for the first HCV patients receiving AVI-4065 Injection
AVI BioPharmas first human use of AVI-4065 Injection involved an open-label multi-center exploratory dose escalating design in healthy adult volunteers The objective of this part of the study was to assess safety tolerability and to design a potentially therapeutic dosage regimen The objective of the second part of the study is to evaluate safety tolerability pharmacokinetics pharmacodynamics and signals of HCV virus response in cohorts of HCV patient volunteers that are interferon and ribavirin treatment failures
The ability of the drug to effect baseline HCV RNA levels over the study duration will be evaluated using a conventional PCR-based assay If there are promising results from this phase of the clinical trial viz a 2 log decrease in HCV RNA levels from baseline within study surveillance it will provide the rational basis for additional clinical testing of AVI-4065 Injection among HCV patients that are treatment refractory viz relapsers and non-responders
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None