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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02765802




Registration number
NCT02765802
Ethics application status
Date submitted
5/05/2016
Date registered
9/05/2016
Date last updated
25/07/2019

Titles & IDs
Public title
A Study to Evaluate Pegylated Interferon Lambda Monotherapy in Patients With Chronic Hepatitis Delta Virus Infection
Scientific title
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)
Secondary ID [1] 0 0
EIG-LMD-001
Universal Trial Number (UTN)
Trial acronym
LIMT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis D, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Peginterferon Lambda-1A

Experimental: Lambda 180 µg - Lambda 180 µg once weekly, administered by subcutaneous (SC) injection, for a total of 48 weeks.

Experimental: Lambda 120 µg - Lambda 120 µg once weekly, administered by subcutaneous (SC) injection, for a total of 48 weeks.


Treatment: Drugs: Peginterferon Lambda-1A


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from baseline in HDV viral load.
Timepoint [1] 0 0
Week 48 (end of treatment)
Primary outcome [2] 0 0
Change from baseline in HDV viral load
Timepoint [2] 0 0
Week 72 (end of follow-up)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Beersheba
Country [2] 0 0
Israel
State/province [2] 0 0
Jerusalem
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
Pakistan
State/province [4] 0 0
Karachi

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eiger BioPharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Lambda is the pegylated form of interferon lambda-1a (IFN-?), a conjugate of recombinant
human interleukin 29 (rIL-29) and a linear polyethylene glycol (PEG) chain. IFN-? and
interferon alpha (IFN-a) share the common interferon (IFN)-stimulated gene induction pathway
that leads to broad-spectrum antiviral activities. Since IFN-a has demonstrated
anti-hepatitis delta virus (HDV) activity in patients with chronic hepatitis delta (CHD), it
is postulated that pegylated IFN-? could also induce HDV ribonucleic acid (RNA) decline in
patients with CHD. Based on IFN-?'s more limited receptor distribution and previous data from
studies involving treatment with IFN-? 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-a 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.
Trial website
https://clinicaltrials.gov/show/NCT02765802
Trial related presentations / 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. 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. 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. Review.
Public notes

Contacts
Principal investigator
Name 0 0
David Apelian, MD, PhD, MBA
Address 0 0
Eiger BioPharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications