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HepatitisPhase 4NCT01443923

Boceprevir Drug Combination for Hepatitis C Treatment in People With and Without HIV

A Phase 4 study testing Boceprevir, Peg-Interferon-alfa 2B and Ribavirin in people with Hepatitis and HIV/AIDS, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Background: Standard treatment for the hepatitis C virus (HCV) is a combination of the drugs peg-IFN and ribavirin. However, this treatment is not very effective in people with a serious type of HCV (HCV genotype 1) and also in people who have human immunodeficiency virus (HIV) coinfection. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis, HIV/AIDS
What is being tested?
Boceprevir, Peg-Interferon-alfa 2B and Ribavirin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
2 sitesUnited States
Study dates
Sep 2011to Sep 2013
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • To be eligible for participation on this protocol, a participant must satisfy all of the following conditions:
  • Be greater than or equal to18 years old and have an identifiable primary care provider.
  • Have documented chronic HCV infection by demonstration of a positive test for hepatitis C antibody and HCV RNA of 2,000 IU/mL or greater.
  • Infected with HCV GT-1 virus.
  • If coinfected, have either documentation of HIV-1 infection by licensed enzyme-linked immunosorbent assay (ELISA) confirmed by a Western Blot or history of HIV RNA of 1,000 copies/mL or greater.
  • If coinfected, must meet one of the following prior to enrollment:
Show all 24Show fewer
  • If on a stable non-NNRTI or non-PI antiretroviral regimen that HAS NOT changed within the past 6 months, must have an HIV-1 VL of less than 400 copies/mL for at least 3 months; or
  • If on a current antiretroviral regimen that HAS changed within the past 6 months, have an HIV-1 VL of less than 50 copies/mL for at least 3 months; or
  • Be a long-term nonprogressor as documented in the medica record.
  • Have histopathologic features consistent with chronic HCV infection at the time of enrollment. A liver biopsy within 3 years (36 calendar months) prior to screening may be used as the baseline biopsy. Participants can opt out of a liver biopsy if they had one more than 3 years prior and have a contraindication, such as receipt of chronic anticoagulation therapy. Participants with decompensated liver disease are excluded from the study.
  • Are na(SqrRoot) ve to prior IFN-based treatment for HCV.
  • Have CD4 cell counts greater than or equal to 100 cells/mm(3).
  • Willing to have genetic testing.
  • Not pregnant or breastfeeding. Serum pregnancy test must be negative at screening for female participants.
  • Agree not to become pregnant if a female of childbearing potential while on the study and for at least 6 months after stopping RBV. Because of the potential teratogenic effects of RBV treatment, subjects and their partners must remain abstinent or use two methods of birth control, which may be selected from the following list (oral contraceptive concentrations are decreased, and may not be effective when used during BOC treatment and, therefore, are not included in this list):
  • Surgical sterilization of either partner
  • Intrauterine device
  • Male or female condoms with or without a spermicide
  • Diaphragm, cervical cap, or sponge
  • Male participants who are not documented to be sterile must agree to either abstain from intercourse or consistently use a condom while their female partner (if applicable) agrees to use one of the appropriate medically accepted methods of birth control listed above from the date of screening until 6 months after the last dose of RBV.
  • Be able and willing to either learn to safely inject medication or find another person to inject the medication for him/her.
  • Be willing to allow storage of blood or tissue samples for future research.
  • Co-enrollment Guidelines:
  • Participants may be enrolled in other NIH protocols as long as the amount of research blood drawn does not exceed the acceptable NIH guidelines and the protocol does not include other experimental therapies (including expanded access/compassionate use of HIV antiretrovirals).

Who cannot join

  • A participant will be ineligible to participate on this study if any of the following criteria are met:
  • Use of other experimental therapies (including expanded access/compassionate use of HIV antiretrovirals) within 30 days or 5 half-lives (whichever is longer), prior to enrollment.
  • Current use of an efavirenz-based (or other NNRTI) or protease inhibitor HIV antiretroviral regimen.
  • Use of any of the following medications within 6 weeks prior to enrollment.
  • Alfuzosin (Uroxatral )
  • Alprazolam (Xanax )
Show all 81Show fewer
  • Atorvastatin (Lipitor )
  • AZT or zidovudine (Retrovir )
  • Carbamazepine (Tegretol )
  • Cisapride (Propulsid )
  • Colchicine (Colcrys ) - If patient has renal or hepatic impairment.
  • DDI or didanosine (Videx )
  • d4T or stavudine (Zerit )
  • Delaviridine (Rescriptor )
  • Digoxin (Lanoxin )
  • Dihydroergotamine
  • Drosperinone (Yaz )
  • Efavirenz (Sustiva )
  • Ergonovine (Ergotrate )
  • Ergotamine (Cafergot )
  • Etravirine (Intelence )
  • Ganciclovir (Cytovene )
  • Immunosuppressive therapy (including oral steroids)
  • ---Use of any use of any immunosuppressive therapy, including systemic steroids (prednisone equivalent of greater than 10 mg/day) for a duration of 6 weeks or more within 6 months prior to enrollment. Use of inhaled/nasal steroids should be avoided.
  • Isoniazid or INH (Ingredient in Rifater )
  • Ketoconazole (Nizoral )
  • Lovastatin (Mevacor )
  • Methylergonovine (Methergine )
  • Midazolam given orally (Versed )
  • Nevirapine (Viramune )
  • Phenobarbital (Luminal )
  • Phenytoin (Dilantin )
  • Pimozide (Orap )
  • Pyrazinamide (Ingredient in Rifater )
  • Rifabutin (Mycobutin )
  • Rifampin/rifampicin
  • Rilpivirine (Edurant )
  • Sildenafil (Viagra ) - Phosphodiesterase type 5 inhibitors are prohibited when used for pulmonary hypertension
  • Simvistatin (Zocor )
  • St. Johns s Wort
  • Tadalafil (Cialis ) - Phosphodiesterase type 5 inhibitors are prohibited when used for pulmonary hypertension
  • Thalidomide (Thalomid )
  • Theophylline (Slo-Phylllin )
  • Triazolam (Halcion )
  • Vardenafil (Levitra ) - Phosphodiesterase type 5 inhibitors are prohibited when used for pulmonary hypertension
  • Warfarin (Coumadin )
  • Zalcitabine (Hivid )
  • There may be other brand names for these products listed above.
  • Has ingested silymarin (milk thistle), s-adenosylmethionine (SAM-e), glycyrrhizin, Sho-saiko-to (SST), or other herbal supplements that may be either liver beneficial or toxic, within 28 days prior to enrollment.
  • Mixed HCV genotypes (e.g., 1 \& 2, 1 \& 3, 1 \& 4) (mixed genotype 1a/1b can be included).
  • Has any other known, or clinically suspected, cause of liver disease, including active hepatitis B.
  • For participants with cirrhosis, a Child Turcotte Pugh score greater than 7, or Child s B or C cirrhosis.
  • Certain abnormal hematological and biochemical parameters, including:
  • Neutrophil count less than1000 cells/mm3
  • Hemoglobin less than10g/dL
  • Platelet count less than or equal to 50,000 cells/mm3
  • Estimated glomerular filtration rate less than50 mL/min/1.73 m(2), calculated automatically by the NIH lab using the original MDRD (modification of diet in renal disease) study equation
  • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than or equal to10 time ULN
  • Prothrombin time International Normalized Ratio (PT-INR) less than2 and/or on chronic anticoagulation medications
  • If total bilirubin is greater than 1.5 mg/dL, then direct bilirubin can be no more than 70% of the total, up to a direct bilirubin of 2.0 mg/dL.
  • Alpha-fetoprotein less than20 ng/mL, unless an ultrasound, computerized tomography scan (CT), or magnetic resonance imaging (MRI) has been performed to rule out hepatoma.
  • Hepatic mass suggestive of hepatocellular carcinoma as detected by ultrasound scan, dual-phase CT, or MRI.
  • History of esophageal or gastric varices.
  • Any neoplastic disease or any nonmetastatic skin, cervical, or anal cancer that has been resected in the past 5 years EXCEPT Kaposi s sarcoma not requiring systemic chemotherapy.
  • Prior organ transplantation other than cornea or hair.
  • Evidence of severe cardiac disease (greater than or equal to Grade 3 congestive cardiac failure, symptomatic coronary artery disease, significant arrhythmias, or uncontrolled hypertension) despite intervention or medical therapy.
  • Evidence of severe chronic pulmonary disease with functional impairment.
  • Severe psychiatric disorder that would interfere with adherence to protocol requirements, and that is not stably treated.
  • Evidence of autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis.
  • Evidence of an uncontrolled seizure disorder defined as more than 1 episode of generalized seizure within the past year.
  • Chronic pancreatitis based on clinical history.
  • History of severe retinopathy.
  • History of hemophilia.
  • Any hemoglobinopathy (e.g., Thalassemia, sickle cell disease).
  • Active systemic infections other than HCV and HIV-1.
  • Evidence of gastrointestinal malabsorption, chronic nausea, or vomiting.
  • Has any systemic illness that will make it unlikely that the participant will be able to return for the required study visits.
  • Any condition that, in the opinion of the investigator, contraindicates participation in this protocol.
  • Because there are insufficient data regarding the safety and efficacy of BOC, PEG, or RBV in the pediatric population, children are excluded from this study.
  • Pregnancy: Pregnant women are excluded from this study because the effects of BOC, PEG, and RBV on the developing human fetus are unknown. Preclinical animal data indicate that the use of RBV treatment during pregnancy is potentially teratogenic.
  • Breastfeeding: Because there is an unknown but potential risk for adverse effects in nursing infants secondary to treatment of the mother with BOC, PEG, or RBV, breastfeeding women are excluded from this study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

  • Unity Health Care, Inc./DC General

    Washington D.C., District of Columbia, 20002

Other trials in United States

About this study

Official title: An Open Label, On-Treatment Trial to Assess the Effect of HIV-1 Coinfection on Therapeutic Responses Using Boceprevir, Peg-Interferon-alfa-2b and Ribavirin in HCV Genotype 1, IFN Treatment-Naive Subjects With or Without HIV-1

Background:

  • Standard treatment for the hepatitis C virus (HCV) is a combination of the drugs peg-IFN and ribavirin. However, this treatment is not very effective in people with a serious type of HCV (HCV genotype 1) and also in people who have human immunodeficiency virus (HIV) coinfection. Researchers want to add a new drug, boceprevir to see if it can improve treatment results in people with both HCV genotype 1 and HIV. Boceprevir used in combination with peg-IFN and ribavirin has been recently approved for the treatment of people with HCV genotype 1 infection only, and is currently being studied in those with HIV and HCV.
Read more

Objectives:

  • To test boceprevir, peg-IFN, and ribavirin as a treatment for HCV genotype 1 in people with HCV monoinfection compared to those with both HIV and HCV infections.

Eligibility:

  • Individuals at least 18 years of age who have HCV genotype 1 infection, and have not received interferon treatment for HCV
  • Half of the study participants will also have HIV infection.

Design:

  • Participants will be screened with a medical history and physical exam. They will also have blood and urine tests.
  • Participants will also have heart and liver function tests, and answer questions about mood and depression.
  • Those in the study will receive ribavirin tablets to take twice a day, and peg-IFN to inject under the skin weekly.
  • Two weeks after starting treatment, participants will have blood tests to study the treatment.
  • Four weeks after starting treatment, participants will start taking boceprevir three times a day.
  • Participants will have regular study visits with blood samples and other tests. The length of therapy will depend on the level of virus detected in the blood at several clinic visits. Those who do not respond well to the medicines at 12 weeks will stop treatment. The full length of treatment is 48 weeks.
Read the detailed description

Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the United States, an estimated 4.1 million people are infected and HCV is the principal cause of death from liver disease and leading indication for liver transplantation. A combination of ribavirin (RBV) and pegylated interferon (peg-IFN) is the currently recommended therapy for chronic HCV infection. However, this therapy achieves viral clearance in only 19% to 52% of patients infected with HCV genotype 1 and 76% to 80% of patients infected with genotypes 2 and 3. Current therapy is also associated with a high incidence of adverse events and low cure rates in several populations. Novel therapies that do not rely on an interferon backbone will be required to enhance cure rates in various populations. Recent data show that adding an HCV serine protease inhibitor (such as boceprevir [BOC]) to peg-IFN and RBV results in HCV eradication rates of 70% to 80% among HCV-monoinfected subjects. However, whether human immunodeficiency virus (HIV)-infected subjects will have similar rates of response to triple combination therapy is presently not known. Previous data have suggested that HIV-infected patients with chronic HCV infection have much lower eradication rates to peg-IFN and RBV than HCV-monoinfected subjects. This study will explore whether HIV/HCV-coinfected subjects have a lower response rate to a BOC/peg-IFN/RBV regimen than HCV-monoinfected subjects. Participants who have chronic hepatitis C genotype 1 monoinfection (N=50) or coinfection with HIV-1 (N=50), and who are na(SqrRoot) ve to IFN-based HCV treatment, will receive combination therapy with BOC (800 mg three times a day, every 7 to 9 hours, with food), weekly peg-IFN alpha-2b (1.5 mcg/kg/week) and twice daily RBV (weight based) for a maximum of 44 weeks, after a 4-week lead-in of peg-IFN and RBV. BOC received recent FDA approval for treating HCV monoinfection in combination with peg-IFN and RBV, and the approved labeling will be followed in this study. The primary endpoint is comparative efficacy in HCV-monoinfected and HIV/HCV-coinfected subjects. Secondary endpoints include determination of host predictors for therapeutic response, emergence of resistance biomarkers, and early viral kinetics. The findings from this study will aid in the understanding of whether HIV infection affects HCV antiviral and host responses to combination therapy using BOC/peg-IFN alfa-2b/RBV.

Conditions
Hepatitis, HIV/AIDS
Being tested
Boceprevir, Peg-Interferon-alfa 2B, Ribavirin
Keywords
Hepatitis, Immunological Response, Virological Response, Resistance Mutations, Viral Kinetics, Hepatitis C, HCV
Medical subject headings
Hepatitis, Acquired Immunodeficiency Syndrome, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BoceprevirDrug

  • Peg-Interferon-alfa 2BDrug

  • RibavirinDrug

Study groups in NCT01443923
Study groupRoleWhat they receive
1-HCVActive comparatorHepatitis C Mono-infected
Receives: Drug: Boceprevir; Drug: Peg-Interferon-alfa 2B; Drug: Ribavirin
2 HCV/HIVActive comparatorHepatitis C and HIV co-Infected
Receives: Drug: Boceprevir; Drug: Peg-Interferon-alfa 2B; Drug: Ribavirin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy, Defined as Sustained Viral Response (SVR) Six Months After the End of Specified Treatment.

    Measured: 6 months post treatment

Secondary outcomes (4)

  1. Change in Early HCV Viral Load Kinetics Between Mono and Co-infected Subjects

    Measured: Day 0, Day 7

  2. Safety and Treatment Outcome Measures Stratified by ESA Use

    Measured: 6 months

  3. Proportion of Subjects Who Are Receiving HAART Who Remain With an HIV RNA & lt; 400 Copies/mL and Those With HIV RNA & gt; 400 Copies/mL at End of Treatment

    Measured: End of Treatment

  4. Efficacy (SVR) Rates as Predicted by Viral Response at the End of the 4-week lead-in Therapy With PEG/RBV and Comparison Between HCV Monoinfected and HIV/HCV Coinfected Subjects

    Measured: 6 months post treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionSep 2013
  4. Study completionSep 2013

Why it stopped: Unable to complete enrollment due to newly approved treatment options.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01443923
Sponsor's protocol ID
110253
Other IDs
11-I-0253
Status last verified
Jul 2015
First submitted
29 Sep 2011
Last updated
13 Jul 2015

Publications

  • Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006 May 16;144(10):705-14. doi: 10.7326/0003-4819-144-10-200605160-00004.

    PubMed 16702586

  • Kim WR. The burden of hepatitis C in the United States. Hepatology. 2002 Nov;36(5 Suppl 1):S30-4. doi: 10.1053/jhep.2002.36791.

    PubMed 12407574

  • Congote LF, Trachewsky D. Qualitative changes in nuclear RNA from rat kidney cortex after aldosterone treatment. Biochem Biophys Res Commun. 1972 Jan 31;46(2):957-63. doi: 10.1016/s0006-291x(72)80234-1. No abstract available.

    PubMed 5057920

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Boceprevir, Peg-Interferon-alfa 2B and Ribavirin in people with Hepatitis and HIV/AIDS, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 81 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy, Defined as Sustained Viral Response (SVR) Six Months After the End of Specified Treatment. (time frame: 6 months post treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01443923, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2015.

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