| Eligibility |
- INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the
following criteria:
- Male or female, >=18 years of age.
- Presence of HDV RNA in serum at two points at least one day apart with HDV RNA levels
that are quantifiable and above the lower limit of quantification (LLOQ) of the HDV
RNA assay.
- Ongoing use of either tenofovir (TDF or TAF) or Entecavir for viral suppression of HBV
for at least 12 weeks with documented suppression of HBV DNA (<100 IU/ml).
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation
in this study:
- Decompensated liver disease, defined by either bilirubin >2mg/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 an absolute
neutrophil count <1000/dL and platelets <75,000/dL will be excluded from the study as
well.
- Pregnancy or lactation.
- For females of reproductive potential: Lack of use of highly effective contraception
defined as tubal ligation in women, or use of two contraceptive methods such as
condoms (male partner) and spermicide in combination with an intrauterine device or a
progestin-based hormonal contraception (implant or injection) for at least 3 months
prior to treatment until 24 weeks after end of study medication administration. Female
participants with childbearing potential must not use oral birth control pills as a
form of contraception due to concern for interaction with study medications leading to
contraception failure.
- For males of reproductive potential: Unable or unwilling to use condoms consistently
in addition to female partner using another adequate contraceptive method to ensure
effective contraception with partner during study participation and for an additional
24 weeks after the end of study medication administration. Patients who have undergone
surgical sterilization (vasectomy) will still require female partner to utilize an
additional adequate contraception method.
- Inability to take oral and subcutaneous medications
- Unwilling to adhere to the study intervention regimen or to comply with study
procedures, or unavailability for the duration of the study
- 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 as determined by self-report or previous medical records.
- 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, previous use of lonafarnib 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.
- Any other condition, which in the opinion of the investigators would impede the
patient s participation or compliance in the study.
- Inability to provide written informed consent.
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