A Study to Evaluate Pegylated Interferon Lambda Monotherapy in Patients With Chronic Hepatitis Delta Virus Infection (LIMT)

A Phase 2 Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Pegylated Interferon Lambda Monotherapy in Patients With Chronic Hepatitis Delta Virus Infection (LIMT)

To evaluate safety and tolerability of lambda over a 48-week treatment period in HDV patients.

Study Overview

• Status: Completed
• Conditions: Hepatitis D, Chronic
• Intervention / Treatment: Drug: Peginterferon Lambda-1A

Detailed Description

Lambda is the pegylated form of interferon lambda-1a (IFN-λ), a conjugate of recombinant human interleukin 29 (rIL-29) and a linear polyethylene glycol (PEG) chain. IFN-λ and interferon alpha (IFN-α) share the common interferon (IFN)-stimulated gene induction pathway that leads to broad-spectrum antiviral activities. Since IFN-α has demonstrated anti-hepatitis delta virus (HDV) activity in patients with chronic hepatitis delta (CHD), it is postulated that pegylated IFN-λ could also induce HDV ribonucleic acid (RNA) decline in patients with CHD. Based on IFN-λ's more limited receptor distribution and previous data from studies involving treatment with IFN-λ in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV), it is postulated that Lambda treatment could be associated with fewer adverse effects than IFN-α treatment. This Phase II study is designed as randomized, open-label study of Lambda 120 or 180 μg subcutaneous (SC) injection weekly for 48 weeks in patients with chronic HDV infection, and the primary objectives of the study are as follows:

• To evaluate the safety and tolerability of treatment with 2 dose levels of Lambda over a 48-week treatment period.
• To evaluate the effect of treatment with 2 different doses of Lambda on HDV RNA levels.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Beersheba, Israel, 84101
    • Soroka Medical Center
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1142
      • Auckland City Hospital
• Pakistan
  • Karachi, Pakistan, 74800
    • The Aga Khan University and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic HDV infection of at least 6 months' duration documented by a positive HDV antibody (Ab) test, detectable and quantifiable HDV RNA by qPCR at study entry
• Serum alanine aminotransferase (ALT) > upper limit of the normal range (ULN) and <10 × ULN at screening
• Electrocardiogram (ECG) demonstrating no acute ischemia or clinically significant abnormality and a QT interval corrected for heart rate (QTcF) <450 ms for male patients and <460 ms for female patients
• Thyroid-stimulating hormone (TSH) and/or free T4 within 0.8 to 1.2 × ULN, or adequately controlled thyroid function as assessed by the investigator.
• Dilated retinal examination ≤1 year before screening
• Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication

Exclusion Criteria:

General Exclusions:

• Participation in a clinical trial with or use of any investigational agent within 30 days before screening, or treatment with interferons (IFNs) or immunomodulators within 12 months before screening
• Previous use of Lambda. Patients who previously participated in a clinical trial of Lambda but are confirmed to have received placebo or other non-Lambda IFNs are allowed.
• History or evidence of any intolerance or hypersensitivity to IFNs or other substances contained in the study medication.
• Female patients who are pregnant or breastfeeding. Male patients must confirm that their female sexual partners are not pregnant.

Exclusions Based on Disease

• Current or previous history of decompensated liver disease (Child-Pugh Class B or C)
• Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)

• Past history or current evidence of decompensated liver disease, defined as any of the following at screening:

  1. Bilirubin level ≥ 2.5 mg/dL unless due to Gilbert's disease
  2. Serum albumin level <3.5 g/dL
  3. International normalized ratio (INR) ≥1.5
  4. Alpha fetoprotein ≥100 ng/mL
• Evidence of significant portal hypertension; current presence or history of variceal bleeding, ascites requiring diuretics or paracentesis, or hepatic encephalopathy

• Any of the following abnormal laboratory test results at screening:

  1. Platelet count <90,000 cells/mm^3
  2. White blood cell count <3,000 cells/mm^3
  3. Absolute neutrophil count <1,500 cells/mm^3
  4. Hemoglobin <11 g/dL for women and <12 g/dL for men
  5. Serum creatinine concentration ≥1.5× ULN
  6. Confirmed creatinine clearance (CrCl) < 50 mL/min by Cockcroft-Gault
• Evidence of another form of viral hepatitis or another form of liver disease
• History of hepatocellular carcinoma

• Patients with any of the following:

  1. Current eating disorder or alcohol abuse
  2. Excessive alcohol intake
  3. In the opinion of the investigator, an alcohol use pattern that will interfere with study conduct
  4. Drug abuse within the previous 6 months before screening, with the exception of cannabinoids and their derivatives

• Prior history or current evidence of any of the following:

  1. Immunologically mediated disease
  2. Retinal disorder or clinically relevant ophthalmic disorder
  3. Any malignancy within 5 years before screening
  4. Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease.
  5. Chronic pulmonary disease
  6. Pancreatitis
  7. Severe or uncontrolled psychiatric disorder
  8. Active seizure disorder
  9. Bone marrow or solid organ transplantation
• Other significant medical condition that may require intervention during the study

Exclusions Based on Concurrent Medication Use

• Therapy with an immunomodulatory agent
• Use of telbivudine
• Current use of heparin or Coumadin
• Received blood products within 30 days before study randomization
• Use of hematologic growth factors within 30 days before study randomization
• Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV within 14 days before study randomization
• Any prescription or herbal product that is not approved by the investigator
• Long-term treatment (> 2 weeks) with agents that have a high risk for nephrotoxicity or hepatotoxicity unless it is approved by the medical monitor
• Receipt of systemic immunosuppressive therapy within 3 months before screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lambda 180 μg; Lambda 180 μg once weekly, administered by subcutaneous (SC) injection, for a total of 48 weeks.	Drug: Peginterferon Lambda-1A; Other Names: Lambda
Experimental: Lambda 120 μg; Lambda 120 μg once weekly, administered by subcutaneous (SC) injection, for a total of 48 weeks.	Drug: Peginterferon Lambda-1A; Other Names: Lambda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HDV Viral Load.	To evaluate the safety and tolerability of treatment with 2 dose levels of Lambda over a 48 week treatment period. To evaluate the effect of treatment with 2 different doses of Lambda on hepatitis D virus (HDV) ribonucleic acid (RNA) levels.	Week 48 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HDV Viral Load	To evaluate the proportion of patients with undetectable HDV RNA 24 weeks after the end of treatment	Week 72 (end of follow-up)
Number of Patients With a Durable Virologic Response	Durable Virologic Response (DVR) = below the limit of quantitation in HDV RNA at 24 weeks post-treatment	Week 72

Collaborators and Investigators

• Sponsor: Eiger BioPharmaceuticals
• Investigators: Study Director: David Apelian, MD, PhD, MBA, Eiger BioPharmaceuticals

Publications and helpful links

General Publications

• Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 2003 Jan;4(1):69-77. doi: 10.1038/ni875. Epub 2002 Dec 16.
• Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol. 2003 Jan;4(1):63-8. doi: 10.1038/ni873. Epub 2002 Dec 2.
• Wedemeyer H, Manns MP. Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead. Nat Rev Gastroenterol Hepatol. 2010 Jan;7(1):31-40. doi: 10.1038/nrgastro.2009.205.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2016
• Primary Completion (Actual): July 20, 2018
• Study Completion (Actual): December 12, 2018

Study Registration Dates

• First Submitted: May 5, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (Estimate): May 9, 2016

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis D; Hepatitis D, Chronic
• Other Study ID Numbers: EIG-LMD-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No