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Efficacy of Pegylated Interferon Plus Ribavirin Plus Nitazoxanide in HCV Genotype 4 and HIV Coinfection

Primary Purpose

HCV Coinfection, HIV Infection

Status

Unknown status

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Nitazoxanide

About this trial

This is an interventional treatment trial for HCV Coinfection focused on measuring HIV, genotype 4 HCV, pegylated interferon, ribavirin, nitazoxanide

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

HIV infection.
Infection with HCV genotype 4.
No prior treatment with any interferon or no response to a previous treatment with Peg-IFN plus RBV. The lack of response will include both nonresponders, and those who showed relapse.
Stable antiretroviral therapy 24 weeks before starting the study drugs, with undetectable plasma HIV RNA during that period of time.
Commitment to use two non-hormonal contraception during the study and up to 24 weeks after treatment.
Acceptance to give written informed consent to participate in the trial.

Exclusion Criteria:

Antiretroviral therapy including didanosine, stavudine, zidovudine and abacavir.
Decompensated cirrhosis.
Presence of other significant liver diseases, including chronic hepatitis or acute hepatitis B, acute hepatitis hepatitis A, hemochromatosis or deficiency of alpha-1 antitrypsin.
Pregnancy and lactation.
Men planning pregnancy with their partners during the study and up to 24 weeks after treatment.
Active or uncontrolled depression, other psychiatric illness, or disease during the previous year which may, in the investigator's opinion, prevent participation in the study.
Previous suicide attempt.
Active thyroid disease or poorly controlled with treatment.
Previous autoimmune diseases such as inflammatory bowel disease, psoriasis serious, or rheumatoid arthritis, which may be exacerbated by interferon.
Chemotherapy or immunomodulatory 24 weeks before starting the study.
Serious illness, including cancer or unstable coronary disease, 24 weeks before starting the study.
Any chronic disease which, in the opinion of the investigator, may prevent complete the study.
Presence of acute or active opportunistic infections 48 weeks before starting the study.
Evidence of hepatocellular carcinoma or alpha-fetoprotein levels ≥ 50 ng / ml, unless an imaging technique shows no evidence of liver tumor, all obtained 24 weeks before starting the study.
Hemoglobinopathy or other conditions that may facilitate hemolysis.
Solid organ or bone marrow transplant.
Known hypersensitivity to any of the drugs under study.
Active consumption of drugs or alcohol in the opinion of the investigator would interfere with participation in the study. The use of methadone or other opiate replacement therapy is not considered an exclusion criterion.
Serious side effects from treatment with Peg-IFN plus RBV in patients with prior failure of such treatment.

Sites / Locations

H.U. Valme

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nitazoxanide

Arm Description

Outcomes

Primary Outcome Measures

Sustained virological response

The proportion of patients with HCV RNA ≤10 IU/ml 24 weeks after finishing the programmed length of treatment (52 weeks).

Secondary Outcome Measures

Safety of Peg-interferon plus ribavirin plus nitazoxanide

The proportion of patients with grade 3 or 4 adverse events according to the WHO classification.

Full Information

NCT ID

NCT01529073

First Posted

February 5, 2012

Last Updated

January 13, 2015

Sponsor

Juan Macías

Collaborators

Spanish National Health System

1. Study Identification

Unique Protocol Identification Number

NCT01529073

Brief Title

Efficacy of Pegylated Interferon Plus Ribavirin Plus Nitazoxanide in HCV Genotype 4 and HIV Coinfection

Official Title

Phase II Clinical Trial to Evaluate the Antiviral Activity of Pegylated Interferon Plus Ribavirin Plus Nitazoxanide in Individuals With Chronic Hepatitis Due to HCV Genotype 4 and Coinfected by HIV

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Unknown status

Study Start Date

February 2012 (undefined)

Primary Completion Date

February 2015 (Anticipated)

Study Completion Date

February 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Juan Macías

Collaborators

Spanish National Health System

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Objectives: 1. Primary objective: To Evaluate the rate of sustained virological response (SVR) of pegylated interferon alfa-2b (Peg-IFN) plus ribavirin (RBV) plus nitazoxanide (NTZ) in patients coinfected by HIV and HCV genotype 4 (HCV-4), never treated before (naïve) and with a treatment failure to a standard therapy with Peg-IFN plus RBV (experienced), and to compare it with the rate of SVR of these patients with Peg-IFN plus RBV is a historical cohort. 2. Secondary objectives: In naive, as well as in experienced patients: a) To evaluate the virological activity at weeks 4 and 12 after starting the combination of Peg-IFN plus RBV plus NTZ in HIV/HCV-4-coinfected patients. b) To analyze the safety of Peg-IFN plus RBV plus NTZ in HIV/HCV-4-coinfected patients. Design: Pilot clinical trial without control to evaluate efficacy and safety (phase II). Patients: Individuals with HIV infection and with confirmed chronic HCV infection. Treatment: NTZ 500 mg every 12 hours during 4 weeks, followed by NTZ 500 mg every 12 hours plus Peg-IFN plus weigh-adjusted RBV for 48 weeks. Total duration of therapy: 52 weeks. Primary variable: The proportion of patients with HCV RNA ≤10 IU/ml 24 weeks after finishing the programmed length of treatment. Secondary variables: 1. The frequency of individuals with HCV RNA ≤10 IU/ml 12 weeks after finishing the programmed length of treatment. 2. The proportion of patients with HCV RNA ≤10 IU/ml at 4 and 12 weeks after adding PegIFN plus RBV to NTZ. 3. The frequency of severe adverse events.

Detailed Description

Main Objective To evaluate the SVR rate of treatment with Peg-IFN alfa-2b plus RBV and NTZ in patients coinfected with HIV and HCV genotype 4, both never exposed to therapy against HCV or who failed a previous treatment with Peg-IFN plus RBV, and to compare with the SVR rate obtained in patients with Peg-IFN plus RBV in a historical cohort. Secondary objectives: In naive, as well as in experienced patients: To evaluate the virological activity at weeks 4 and 12 after starting the combination of Peg-IFN plus RBV plus NTZ in HIV/HCV-4-coinfected patients. To analyze the safety of Peg-IFN plus RBV plus NTZ in HIV/HCV-4-coinfected patients. Design Single arm pilot clinical trial to evaluate safety and efficacy (phase II). Disease or disorder under study Coinfection with HIV and HCV genotype 4. Drugs under study Nitazoxanide 500 mg every 12 hours for 4 weeks followed by nitazoxanide 500 mg every 12 hours plus pegylated interferon alfa-2b 1.5 mcg/kg/week and weight-adjusted ribavirin for 48 weeks. Study Population and total number of subjects Patients infected with HIV-1 with chronic HCV genotype 4 who meet the selection criteria. Number of patients included in the study: 45.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HCV Coinfection, HIV Infection

Keywords

HIV, genotype 4 HCV, pegylated interferon, ribavirin, nitazoxanide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nitazoxanide

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Nitazoxanide

Other Intervention Name(s)

Alinia, Annita, Daxon, Dexidex, Kidonax, Mitafar, Pacovanton, Paramix, Nitax, Zox, Nitazox, Niazid, Toza

Intervention Description

Nitazoxanide 500 mg bid po for 4 weeks, followed by nitazoxanide 500 mg bid plus pegylated interferon alpha 2b 1.5 mg/kg/week sc plus weight-adjusted ribavirin po for 48 weeks.

Primary Outcome Measure Information:

Title

Sustained virological response

Description

The proportion of patients with HCV RNA ≤10 IU/ml 24 weeks after finishing the programmed length of treatment (52 weeks).

Time Frame

24 weeks after finishing the scheduled treatment

Secondary Outcome Measure Information:

Title

Safety of Peg-interferon plus ribavirin plus nitazoxanide

Description

The proportion of patients with grade 3 or 4 adverse events according to the WHO classification.

Time Frame

Every 4 weeks until 28 weeks of treatment, then every 8 weeks until the end of treatment (52 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HIV infection. Infection with HCV genotype 4. No prior treatment with any interferon or no response to a previous treatment with Peg-IFN plus RBV. The lack of response will include both nonresponders, and those who showed relapse. Stable antiretroviral therapy 24 weeks before starting the study drugs, with undetectable plasma HIV RNA during that period of time. Commitment to use two non-hormonal contraception during the study and up to 24 weeks after treatment. Acceptance to give written informed consent to participate in the trial. Exclusion Criteria: Antiretroviral therapy including didanosine, stavudine, zidovudine and abacavir. Decompensated cirrhosis. Presence of other significant liver diseases, including chronic hepatitis or acute hepatitis B, acute hepatitis hepatitis A, hemochromatosis or deficiency of alpha-1 antitrypsin. Pregnancy and lactation. Men planning pregnancy with their partners during the study and up to 24 weeks after treatment. Active or uncontrolled depression, other psychiatric illness, or disease during the previous year which may, in the investigator's opinion, prevent participation in the study. Previous suicide attempt. Active thyroid disease or poorly controlled with treatment. Previous autoimmune diseases such as inflammatory bowel disease, psoriasis serious, or rheumatoid arthritis, which may be exacerbated by interferon. Chemotherapy or immunomodulatory 24 weeks before starting the study. Serious illness, including cancer or unstable coronary disease, 24 weeks before starting the study. Any chronic disease which, in the opinion of the investigator, may prevent complete the study. Presence of acute or active opportunistic infections 48 weeks before starting the study. Evidence of hepatocellular carcinoma or alpha-fetoprotein levels ≥ 50 ng / ml, unless an imaging technique shows no evidence of liver tumor, all obtained 24 weeks before starting the study. Hemoglobinopathy or other conditions that may facilitate hemolysis. Solid organ or bone marrow transplant. Known hypersensitivity to any of the drugs under study. Active consumption of drugs or alcohol in the opinion of the investigator would interfere with participation in the study. The use of methadone or other opiate replacement therapy is not considered an exclusion criterion. Serious side effects from treatment with Peg-IFN plus RBV in patients with prior failure of such treatment.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan Macías, MD, PhD

Organizational Affiliation

Infectious Diseases and Microbiology Unit. Hospital Universitario de Valme. Servicio Andaluz de Salud

Official's Role

Principal Investigator

Facility Information:

Facility Name

H.U. Valme

City

Seville

ZIP/Postal Code

41014

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

26640956

Citation

Macias J, Lopez-Cortes LF, Tellez F, Recio E, Ojeda-Burgos G, Rios MJ, Rivero-Juarez A, Delgado M, Rivas-Jeremias, Pineda JA. Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection. PLoS One. 2015 Dec 7;10(12):e0143492. doi: 10.1371/journal.pone.0143492. eCollection 2015.

Results Reference

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Efficacy of Pegylated Interferon Plus Ribavirin Plus Nitazoxanide in HCV Genotype 4 and HIV Coinfection

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