Ignite Creation Date:
2024-05-05 @ 10:45 PM
Last Modification Date:
2024-10-26 @ 10:24 AM
Study NCT ID:
NCT01185028
Status:
COMPLETED
Last Update Posted:
2021-10-05
First Post:
2010-08-18
Brief Title:
A Safety and Tolerability Study of Nitazoxanide in HIV-HCV Treatment Failures
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Open-Label Safety and Tolerability Study of Nitazoxanide Pegylated-Interferon Alfa 2a and Ribavirin in HIVHCV Co-Infected Genotype 1 Prior Treatment Relapsers and Non-Responders
Status:
COMPLETED
Status Verified Date:
2013-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Chronic hepatitis C CHC is a major health problem that particularly affects individuals with human immunodeficiency virus HIV infection and can lead to cirrhosis and liver failure Standard treatment for people with HIV and CHC is a 48-week course of pegylated-interferon alfa 2a peg-IFN and ribavirin RBV but better treatments are needed for those who either do not respond to the drugs or who relapse after treatment
Nitazoxanide has been approved by the Food and Drug Administration primarily to treat diarrhea caused by parasites and it has been studied in the treatment of CHC infection However it has not been tested in persons infected with HIV and CHC co-infection Researchers are interested in determining whether nitazoxanide is a safe and tolerable treatment for CHC in individuals with HIV
Objectives
- To assess the safety and tolerability of using nitazoxanide to treat chronic hepatitis C infection in individuals with HIV who have not responded to standard treatment for hepatitis C
Eligibility
- Individuals at least 18 years of age who have been diagnosed with both HIV and chronic hepatitis C and who have either not responded to or relapsed after previous hepatitis C treatment
Design
Participants will be screened with a physical examination and medical history blood and urine tests imaging studies possible heart lung and psychological tests and a liver biopsy if one has not been done in the past 3 years
Participants will receive nitazoxanide the medication being studied to take by mouth for 4 weeks and will provide blood samples during this time
After 4 weeks participants will receive the first dose of peg-IFN and RBV Participants will have weekly injections of peg-IFN and continue to take nitazoxanide and RBV by mouth for 48 weeks Individuals who are slow to respond to this combined CHC treatment nitazoxanide peg-IFN and RBV by week 12 will continue to have the combined treatment for an extended period a total of 72 weeks
Participants will have study visits to provide blood samples and have other tests two times in the first month of combined treatment and then at months 2 3 4 7 10 13 19 and month 25 only in participants slow to respond to combined treatment
Some participants who are on specific HIV treatment regimens may enroll in a substudy that will require three separate 12-hour visits for repeated blood samples and other tests during the initial 4-week nitazoxanide treatment
Chronic hepatitis C CHC is a major health problem that particularly affects individuals with human immunodeficiency virus HIV infection and can lead to cirrhosis and liver failure Standard treatment for people with HIV and CHC is a 48-week course of pegylated-interferon alfa 2a peg-IFN and ribavirin RBV but better treatments are needed for those who either do not respond to the drugs or who relapse after treatment
Nitazoxanide has been approved by the Food and Drug Administration primarily to treat diarrhea caused by parasites and it has been studied in the treatment of CHC infection However it has not been tested in persons infected with HIV and CHC co-infection Researchers are interested in determining whether nitazoxanide is a safe and tolerable treatment for CHC in individuals with HIV
Objectives
- To assess the safety and tolerability of using nitazoxanide to treat chronic hepatitis C infection in individuals with HIV who have not responded to standard treatment for hepatitis C
Eligibility
- Individuals at least 18 years of age who have been diagnosed with both HIV and chronic hepatitis C and who have either not responded to or relapsed after previous hepatitis C treatment
Design
Participants will be screened with a physical examination and medical history blood and urine tests imaging studies possible heart lung and psychological tests and a liver biopsy if one has not been done in the past 3 years
Participants will receive nitazoxanide the medication being studied to take by mouth for 4 weeks and will provide blood samples during this time
After 4 weeks participants will receive the first dose of peg-IFN and RBV Participants will have weekly injections of peg-IFN and continue to take nitazoxanide and RBV by mouth for 48 weeks Individuals who are slow to respond to this combined CHC treatment nitazoxanide peg-IFN and RBV by week 12 will continue to have the combined treatment for an extended period a total of 72 weeks
Participants will have study visits to provide blood samples and have other tests two times in the first month of combined treatment and then at months 2 3 4 7 10 13 19 and month 25 only in participants slow to respond to combined treatment
Some participants who are on specific HIV treatment regimens may enroll in a substudy that will require three separate 12-hour visits for repeated blood samples and other tests during the initial 4-week nitazoxanide treatment
Detailed Description:
Chronic hepatitis C CHC viral infection is a major health problem affecting 130-170 million worldwide and 27-39 million in the US more than 3 times those with HIV infection One-third of persons with HIV have CHC a more rapid progression to cirrhosis and liver failure with liver disease as one of the leading causes of mortality
Standard treatment pegylated-interferon IFN alfa and ribavirin RBV has an efficacy sustained virologic response SVR of less than 50 in those with HCV genotype 1 GT 1 and only about 25 of those with HIV-HCV GT1 co-infection SVR is even lower in those retreated who were prior treatment relapsers or non-responders few published studies exist especially in those with HIV Improved therapy is imperative given increasing morbidity and mortality and the proportion of persons who are relapsers or non-responders Newer and promising anti-HCV therapies directly acting antivirals DAA are in development However only 2 are in Phase 3 clinical trials and most remain far from FDA approval
An oral agent nitazoxanide NTZ with broad in vitro anti-microbial activity and a good safety profile has higher efficacy rates in treatment na ve participants mono-infected with HCV GT 1 or 4 There have not been studies in HIV co-infected persons nor pharmacokinetic PK studies in liver or renal disease In vitro studies suggest that NTZ has both a direct suppressive effect on HCV replication as well as a sensitizing effect on IFN-mediated suppression of HCV replication yet the exact mechanism of action giving rise to higher SVR rates is not well understood
This is an open-label study in 35 HIV-HCV GT 1 co infected persons prior relapsers n25 or non-responders n10 after a full course of IFN and RBV therapy Participants will receive 4 weeks of NTZ lead-in therapy followed by NTZpeg-IFNRBV triple combination therapy for an additional 48 weeks Slow responders will receive 72 weeks of triple therapy after the 4-week NTZ lead-in
The primary endpoint is safety and tolerability of NTZ Secondary endpoints are exploratory 1 efficacy rate estimation 2 viral dynamics assessment and determination of predictive response 3 pharmacologic level assessment 4 indirect mechanistic action evaluation of NTZ through virologic response and 5 IFN-stimulated genetic expression evaluation and determination of predictive response There will be a sub-study evaluating the PK of NTZ in a group of 10 participants who are on a ritonavir-based HIV antiretroviral regimen
Standard treatment pegylated-interferon IFN alfa and ribavirin RBV has an efficacy sustained virologic response SVR of less than 50 in those with HCV genotype 1 GT 1 and only about 25 of those with HIV-HCV GT1 co-infection SVR is even lower in those retreated who were prior treatment relapsers or non-responders few published studies exist especially in those with HIV Improved therapy is imperative given increasing morbidity and mortality and the proportion of persons who are relapsers or non-responders Newer and promising anti-HCV therapies directly acting antivirals DAA are in development However only 2 are in Phase 3 clinical trials and most remain far from FDA approval
An oral agent nitazoxanide NTZ with broad in vitro anti-microbial activity and a good safety profile has higher efficacy rates in treatment na ve participants mono-infected with HCV GT 1 or 4 There have not been studies in HIV co-infected persons nor pharmacokinetic PK studies in liver or renal disease In vitro studies suggest that NTZ has both a direct suppressive effect on HCV replication as well as a sensitizing effect on IFN-mediated suppression of HCV replication yet the exact mechanism of action giving rise to higher SVR rates is not well understood
This is an open-label study in 35 HIV-HCV GT 1 co infected persons prior relapsers n25 or non-responders n10 after a full course of IFN and RBV therapy Participants will receive 4 weeks of NTZ lead-in therapy followed by NTZpeg-IFNRBV triple combination therapy for an additional 48 weeks Slow responders will receive 72 weeks of triple therapy after the 4-week NTZ lead-in
The primary endpoint is safety and tolerability of NTZ Secondary endpoints are exploratory 1 efficacy rate estimation 2 viral dynamics assessment and determination of predictive response 3 pharmacologic level assessment 4 indirect mechanistic action evaluation of NTZ through virologic response and 5 IFN-stimulated genetic expression evaluation and determination of predictive response There will be a sub-study evaluating the PK of NTZ in a group of 10 participants who are on a ritonavir-based HIV antiretroviral regimen
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 10-CC-0183 | None | None | None |