Peginterferon Lambda and Lonafarnib Boosted With Ritonavir 48-Week Combination Therapy for Delta Hepatitis

NCT05953545 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 10001515001515-DK
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Chronic hepatitis D is a serious liver disease caused by a virus. Currently, no medications are approved to treat chronic hepatitis D. Objective: To test a combination of 3 drugs in people with chronic hepatitis D. Eligibility: People 18 years or older with chronic hepatitis D. Design: Participants will be in the study about 2 years. They will have 3 inpatient stays of 3 to 5 days. Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function and an ultrasound: a wand that uses sound waves to create images of the liver will be rubbed over the skin on their torso. Participants will stay in the clinic for a 3-day baseline visit. They will have imaging scans, an eye exam, and a visit with a reproductive specialist. They will have a liver biopsy: about 1 inch of liver tissue will be removed, either with a tube inserted through a vein in the neck, or with a needle inserted through the participant s side. Participants will take the study drugs for 48 weeks. Two of them are tablets taken twice a day at home; 1 is a shot administered once a week. Participants will begin taking the drugs during a 5-day stay in the clinic. Then they will have 15 outpatient visits while taking the drugs and 7 more after they finish. The last 3-day clinic stay will be 6 months after participants finish taking the drugs. The liver biopsy, imaging scans, and other tests will be repeated.

Conditions

Chronic Hepatitis Delta

Keywords

Hepatitis D; pegylated interferon lambda; Sustained Virological Response

Outcome Measures

Primary Outcomes (1)

• The goal of this study is to assess the therapeutic response to 48 weeks of treatment with peginterferon lambda and lonafarnib boosted with ritonavir in patients with chronic hepatitis D.

  This is a phase 2 study evaluating the efficacy and safety of a novel regimen for the treatment of chronic HDV infection.

  48 weeks

Study Arms (1)

Peginterferon Lambda

EXPERIMENTAL

A weekly subcutaneous injection of peginterferon lambda at a dose of 180 mcg and an oral twice daily dosing of Lonafarnib at 50mg boosted with twice daily Ritonavir at 100mg for 48 weeks. Following 48 weeks of treatment the subjects will be monitored for outcomes during an additional 6-month time period.

Drug: Peginterferon Lambda

Interventions

Peginterferon Lambda DRUG

Study intervention for this protocol includes a weekly subcutaneous injection of peginterferon lambda at a dose of 180 mcg and an oral twice daily dosing of Lonafarnib at 50mg boosted with twice daily Ritonavir at 100mg for 48 weeks. Following 48 weeks of treatment the subjects will be monitored for outcomes during an additional 6-month time period.

Peginterferon Lambda

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hepatitis D, Chronic; Hepatitis D

Interventions

peginterferon lambda-1a

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christopher Koh, M.D.

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

  PRINCIPAL INVESTIGATOR

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: July 19, 2023
• First Posted: July 20, 2023
• Study Start: May 22, 2024
• Primary Completion: May 22, 2024
• Study Completion: May 22, 2024
• Last Updated: May 23, 2024

Record last verified: 2024-05

Locations

US (1)