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Protocol Details

Treatment of Chronic Delta Hepatitis with Lonafarnib, Ritonavir and Lambda Interferon

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

18-DK-0123

Sponsoring Institute

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

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Hepatitis D;
Hepatitis D Virus;
Cirrhosis

Recruitment Keyword(s)

None

Condition(s)

Liver Disease;
Hepatitis D

Investigational Drug(s)

lonafarnib
Interferon Lambda 1a

Investigational Device(s)

None

Intervention(s)

Drug: Peg-interferon lambda
Drug: Lonafarnib
Drug: Ritonavir

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

Background:

Infection with hepatitis D virus leads to a chronic liver disease with no effective treatment. Lonafarnib has improved hepatitis D virus levels in blood, but the medication still needs more research. Ritonavir makes other drugs more effective and is used with lonafarnib to make it more effective. Lambda interferon stimulates the body s response to viruses. Researchers want to see if combining these drugs fights hepatitis D and helps the liver.

Objectives:

To see if combining lonafarnib, ritonavir, and lambda interferon is safe and effective to treat chronic hepatitis D infection.

Eligibility:

Adults at least 18 years old with chronic hepatitis D infection

Design:

Participants will be screened with a physical exam, medical history, and blood and urine tests.

Throughout the study, all participants will:

-Follow rules for medicine, food, and contraception

-Take hepatitis B medicine

-Have weight checked

-Have routine blood and urine tests

-Give stool samples

-Female participants will have pregnancy tests.

Participants will have 3 visits before treatment. They will repeat screening tests and have a heart test and liver scan.

Participants will have a 5-day inpatient stay. They will:

-Baseline blood and urine tests

-Have eye tests

-Answer health questions

-Have a liver sample taken and liver blood pressure measured. Participants will be sedated.

-Have reproductive tests

-Start the study drugs and have blood draws

Over 24 weeks of treatment, participants will:

-Take 2 study drugs by mouth every day and 1 as a weekly injection

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Eligibility

INCLUSION CRITERIA:

-Age 18 years or above, male or female.

-Presence of anti-HDV in serum.

-Presence of quantifiable HDV RNA in serum at three time pre-treatment points with a mean HDV RNA level >2 log10 above the lower limit of quantification (LLOQ) of the HDV RNA assay.

-Demonstration of chronicity as evidenced by the presence of HDV RNA in serum for >/= 6 months, or presence of Anti-HDV antibody >/= 6months.

INCLUSION CRITERIA:

-Decompensated liver disease, defined by bilirubin >4mg/dL, albumin <3.0 gm/dL, prothrombin time >2 sec prolonged, or history of bleeding esophageal varices, ascites or hepatic encephalopathy. Laboratory abnormalities that are not thought to be due to liver disease may not necessarily require exclusion. Patients with ALT levels greater than 1000 U/L (>25 times ULN) will not be enrolled but may be followed until three determinations are below this level. Patients with an absolute neutrophil count <1000/dL and platelets <75,000/dL will be excluded from the study as well.

-Pregnancy, active breast-feeding, or inability to practice adequate contraception, in women of childbearing potential or in partners of such women. Adequate contraception is defined as vasectomy in male sexual partners of female participants, tubal ligation in women, or use of two contraceptive methods such as condoms and spermicide combination with 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 (eGFR <50 ml/min), organ transplantation, serious psychiatric disease or depression (only if felt to be at high risk by the NIH psychiatric consultation service), or active coronary artery disease.

-Systemic immunosuppressive therapy within the previous 2 months before enrollment.

-Evidence of another form of liver disease in addition to viral hepatitis (for example autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson disease, alcoholic liver disease, ongoing drug induced liver disease, nonalcoholic steatohepatitis (but not steatosis), hemochromatosis, or alpha-1-antitrypsin deficiency).

-Active substance abuse, such as alcohol, inhaled or injection drugs within the previous year.

-Evidence of hepatocellular carcinoma. This will be determined on the basis of imaging with ultrasound/ CT scan or MRI performed a maximum of 6 months prior to enrollment. Elevated AFP levels will be evaluated clinically and further imaging may be performed if felt necessary.

-Evidence of concurrent hepatitis C infection with positive serum HCV RNA.

-Any experimental therapy or pegylated interferon therapy within 6 months prior to enrollment.

-Active, serious autoimmune disease such as systemic lupus erythematosus, ulcerative colitis, Crohn s disease or rheumatoid arthritis, that is in the opinion of the investigators might be exacerbated by therapy with lambda interferon. This will be evaluated at baseline and during follow-up laboratory testing (including blood and urine studies) in addition to described symptoms at each outpatient visit.

-Diagnosis of malignancy in the five years prior to the enrollment with exception granted to superficial dermatologic malignancies.

-Evidence of HIV co-infection; HIV 1/2 antibody positivity on serum testing.

-Concurrent usage of statins as these drugs inhibits mevalonate synthesis, which reduces protein prenylation.

-Concurrent usage of moderate and strong CYP3A inhibitors and inducers.

-Concurrent usage of alpha 1 adrenoreceptor antagonist, antiarrhythmic, pimozide, sildenafil, sedative and hypnotics, ergot and St. John s Wort due to possible effect of ritonavir on hepatic metabolism of these drugs resulting in potentially life-threatening side effects.

-Clinically significant baseline EKG abnormalities such as QTc interval >450 ms and/or prolonged PR interval.

-Uncontrolled elevated triglycerides (>500 mg/dL). Patients on lipid lowering therapy other than statins will be eligible for this study.

-History of pancreatitis from causes other than gallstone pancreatitis. Subjects with a baseline amylase and/or lipase level >3 ULN will be excluded from the study.

-Inability to understand or sign informed consent.

-Any other condition, which in the opinion of the investigators would impede the patient s participation or compliance in the study.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Christopher Koh, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)



Amy (Wen-Chun) Huang
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Building 10
Room 4-5722
10 Center Drive
Bethesda, Maryland 20892
(301) 451-6983
wen-chun.huang@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03600714

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