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

NCT03600714 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 18012318-DK-0123
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Liver Disease; Hepatitis D

Keywords

Hepatitis D; Hepatitis D Virus; Cirrhosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs

  Decline of HDV RNA viral titer of \>2 logs from baseline at 24 weeks of therapy

  Baseline and 24 weeks

• Number of Participants Who Discontinue Medication

  Discontinuation of the medication before 24 weeks by the clinical team or patient will be considered a failure to tolerate the medicine.

  24 weeks

Secondary Outcomes (10)

• Number of Participants With Sustained Virologic Response

  12 and 24 weeks after completing therapy

• Number of Participants With Reduction in Histologic Inflammatory Scores (Modified HAI)

  End of treatment and 24 weeks after completing therapy.

• Number of Participants With Normalization of Serum ALT

  End of therapy, and 12 and 24 weeks after completing therapy

• Number of Participants With Reduction of Hepatic Venous Pressure Gradient (HVPG)

  Baseline and 24 weeks after completing therapy

• Number of Participants With Reduction in Fibroscan Transient Elastography Values

  Baseline and 24 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Treatment with Lonafarnib, Ritonavir, and Peginterferon lambda

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

Interventions

Peg-interferon lambda DRUG

Peg-interferon Lambda is a covalent conjugate of human recombinant non- pegylated interferon (IFN) lambda and a 20-kDa linear pegylated (PEG) chain.

Treatment

Lonafarnib DRUG

Oral prenylation inhibitor

Treatment

Ritonavir DRUG

Booster of lonafarnib action

Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 alpha fetoprotein (AFP) levels will be evaluated clinically and further imaging may be performed if felt necessary.
• Evidence of concurrent hepatitis C infection with positive serum hepatitis C virus (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 CYTOCHROME P-450 CYP3A (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 corrected QT (QTc) interval \>450 ms and/or prolonged PR interval.

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

Liver Diseases; Hepatitis D; Fibrosis

Interventions

lonafarnib; Ritonavir

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Christopher Koh
• Organization: NIDDK

kohchris@mail.nih.gov

301-443-9402

Study Officials

• Christopher Koh, 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: July 25, 2018
• First Posted: July 26, 2018
• Study Start: August 1, 2018
• Primary Completion: February 5, 2020
• Study Completion: August 11, 2020
• Last Updated: December 14, 2021
• Results First Posted: December 1, 2021

Record last verified: 2021-12

Locations

US (1)