NCT00023322

Brief Summary

This study will evaluate the safety and effectiveness of a long-acting form of alpha interferon called pegylated interferon in treating hepatitis D virus (HDV) infection. HDV only infects people who already have hepatitis B infection. HDV is often severe and progressive. Alpha interferon is the standard treatment for HDV, given by injection once a day or three times a week for up to 12 months. However, this treatment does not work for everyone, and those who respond usually relapse when the drug is stopped. The sustained-release form of the drug, pegylated interferon, is given just once a week. Pegylated interferon is more effective than standard interferon in hepatitis C patients, with patients experiencing longer-term improvement. This study will evaluate the effects of pegylated interferon on hepatitis D and hepatitis B. It will determine whether long-term therapy with this drug improves inflammation and scarring of the liver, thereby delaying or reversing cirrhosis, and whether the improvement can be maintained. Patients with chronic hepatitis D over 6 years old may be eligible for this study. Participants will have a medical evaluation, including a history and physical examination, blood tests, routine urinalysis and 24-hour urine collection. Chest X-ray, electrocardiogram, abdominal ultrasound and liver biopsy will be done if these tests have not been done within the last year. In addition, depending on their age and individual health status, some patients may have exercise stress testing, an eye examination, hearing test, and psychiatric consultation. All patients will fill out a health-related quality of life questionnaire. Patients will receive pegylated interferon by injection once a week and have blood tests to measure the effects of treatment on the liver and on HBV and HDV levels. The medical examination and liver biopsy will be repeated at the end of 12 months. Patients who improved with treatment may continue therapy long-term. Medical evaluations and liver biopsies will be repeated at 3 years and at 5 years.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2001

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2001

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

September 3, 2001

Completed
Same day until next milestone

First Posted

Study publicly available on registry

September 3, 2001

Completed
10.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2012

Completed
9 months until next milestone

Results Posted

Study results publicly available

July 10, 2013

Completed
Last Updated

July 10, 2013

Status Verified

July 1, 2013

Enrollment Period

10.8 years

First QC Date

September 3, 2001

Results QC Date

April 15, 2013

Last Update Submit

July 9, 2013

Conditions

Hepatitis D

Keywords

CirrhosisChronic HepatitisAlpha InterferonHepatitis D VirusDelta HepatitisViral HepatitisAntiviral AgentsHepatitis DHDVLiverHepatitis

Outcome Measures

Primary Outcomes (1)

  • Histological Response at 3 Years

    Histological response is defined as at least 3 point improvement in inflammatory score or 1 point improvement in fibrosis score of the HAI at each liver biopsy.

    3 years

Secondary Outcomes (1)

  • Histological Response at 5 Years

    5 years

Study Arms (1)

Peginterferon Alpha-2a

EXPERIMENTAL

Patients with hepatitis D virus (HDV) infection are treated with pegylated alpha interferon therapy for 3 years. The dose of the drug is 180 mcg/week.

Drug: Peginterferon Alpha-2a

Interventions

Peginterferon Alpha-2aDRUG

Treatment

Peginterferon Alpha-2a

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age greater than or equal to 18 years, male or female
  • Serum alanine or aspartate aminotransferase activities that are above the upper limit of normal (ALT greater than 41 or AST greater than 31 U/L) on an average of three determinations taken during the previous 6 months. The mean of the three determinations will be defined as 'baseline' levels.
  • Presence of anti-HDV in serum.
  • Evidence of chronic hepatitis on liver biopsy done within the previous 12 months with a necroinflammatory score in histology activity index of at least 5 (out of a maximum of 18) and at least 1 for hepatic fibrosis (out of a maximum of 6).
  • Presence of HDV antigen in liver tissue.
  • Written informed consent.
  • Previous standard alpha interferon or other antiviral activity will not exclude patients.
  • Active HBV replication will not exclude patients.
  • All ethnicities.
  • Patients will need to meet the first six entry criteria to enroll.

You may not qualify if:

  • Decompensated liver disease, as marked by bilirubin greater than 4 mg%, albumin less than 3.0 gm%, prothrombin time greater than 2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy. Patients with ALT levels greater than 1000 U/L (greater than 25 times ULN) will not be enrolled but may be followed until three determinations are below this level.
  • Pregnancy or, in women of child-bearing potential or in spouses of such women, inability to practice adequate contraception defined as vasectomy in men, tubal ligation in women, or use of condoms and spermicide, or birth control pills, or an intrauterine device, or Depo-Provera, or Norplant.
  • Significant systemic or major illnesses other than liver disease, including, but not limited to, congestive heart failure, renal failure (creatinine clearance less than 50 ml/min), organ transplantation, serious psychiatric disease or depression (only if felt to be at high risk by the NIH psychiatric consultation service), and angina pectoris.
  • Immunosuppressive therapy within the last 6 months.
  • Evidence of another form of liver disease in addition to viral hepatitis (for example autoimmune liver disease, Wilson's disease, alcoholic liver disease, hemochromatosis, and alpha-1-antitrypsin deficiency).
  • Any evidence of coronary artery disease or cerebral vascular disease, including abnormalities on exercise stress testing in patients with defined risk factors who will be screened for evidence of underlying coronary artery disease.
  • Active substance abuse, such as alcohol, inhaled or injection drugs within the previous year.
  • Evidence of hepatocellular carcinoma; either alphafetoprotein (AFP) levels greater than 200 ng/ml (normal less than 9 ng/ml) and/or ultrasound (or other imaging study) demonstrating a mass suggestive of liver cancer.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

  • Verme G, Brunetto MR, Oliveri F, Baldi M, Forzani B, Piantino P, Ponzetto A, Bonino F. Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci. 1991 Aug;36(8):1134-6. doi: 10.1007/BF01297460.

    PMID: 1650690BACKGROUND

  • Rizzetto M, Ponzetto A, Forzani I. Hepatitis delta virus as a global health problem. Vaccine. 1990 Mar;8 Suppl:S10-4; discussion S21-3. doi: 10.1016/0264-410x(90)90207-3.

    PMID: 2183511BACKGROUND

  • Rizzetto M, Verme G, Recchia S, Bonino F, Farci P, Arico S, Calzia R, Picciotto A, Colombo M, Popper H. Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. Ann Intern Med. 1983 Apr;98(4):437-41. doi: 10.7326/0003-4819-98-4-437.

    PMID: 6340574BACKGROUND

  • Hercun J, Kim GE, Da BL, Rotman Y, Kleiner DE, Chang R, Glenn JS, Hoofnagle JH, Koh C, Heller T. Durable virological response and functional cure of chronic hepatitis D after long-term peginterferon therapy. Aliment Pharmacol Ther. 2021 Jul;54(2):176-182. doi: 10.1111/apt.16408. Epub 2021 May 28.

    PMID: 34048594DERIVED

  • Kefalakes H, Koh C, Sidney J, Amanakis G, Sette A, Heller T, Rehermann B. Hepatitis D Virus-Specific CD8+ T Cells Have a Memory-Like Phenotype Associated With Viral Immune Escape in Patients With Chronic Hepatitis D Virus Infection. Gastroenterology. 2019 May;156(6):1805-1819.e9. doi: 10.1053/j.gastro.2019.01.035. Epub 2019 Jan 18.

    PMID: 30664876DERIVED

Related Links

MeSH Terms

Conditions

Hepatitis DFibrosisHepatitis, ChronicHepatitis

Condition Hierarchy (Ancestors)

Hepatitis, Viral, HumanVirus DiseasesInfectionsRNA Virus InfectionsLiver DiseasesDigestive System DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsChronic DiseaseDisease Attributes

Results Point of Contact

Title
Theo Heller, M.D.
Organization
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Theoh@mail.nih.gov
(301) 402-7147

Study Officials

  • Theo Heller, M.D.

    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 3, 2001

First Posted

September 3, 2001

Study Start

August 1, 2001

Primary Completion

May 1, 2012

Study Completion

October 1, 2012

Last Updated

July 10, 2013

Results First Posted

July 10, 2013

Record last verified: 2013-07

Locations

US(1)