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OpenTrials
Completed

NCT Number: NCT01204762

Dose Ranging Study of Pegylated Interferon Lambda in Patients With Hepatitis B and Positive for the Hepatitis B e Antigen

At least 1 dose of pegIFNλ will be identified which is safe, well tolerated, and efficacious for the treatment of chronic hepatitis B virus infection (CHB)

Amendment 7, Part B Sub Study: The primary purpose of this amendment is to obtain preliminary data on the safety of pegylated interferon Lambda (Lambda) when administered in combination with Entecavir(ETV) to patients with hepatitis E antigen-positive (HBeAg-positive) chronic hepatitis B(CHB) infection employing a sequential therapy approach

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Key information

Conditions

Hepatitis B Virus Blood-Borne Infections Communicable Diseases DNA Virus Infections Digestive System Diseases Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis, Viral, Human Infections Liver Diseases Virus Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution, Camperdown, New South Wales, Australia

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About this study

Part B sub study is Open Label

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Infection with the hepatitis B virus (HBV) and positive for the hepatitis B e antigen
  • Between the ages of 18 and 70
  • Have not been previously treated with an interferon
  • HBV nucleos(t)ide-naive

Exclusion criteria

  • Not infected with the hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
  • Do not have a serious liver, psychiatric, blood, thyroid, lung, heart or eye disease
  • Able to tolerate oral medication

Treatment and study plan

pegIFN

Drug

Syringe, Subcutaneous, 180 μg, Once Weekly, 48 weeks

PegIFNα-2a

Drug

Syringe, Subcutaneous 180 μg, Once Weekly, 48 Weeks

Other names: Pegasys

PegIFN lambda

Drug

Syringe, Subcutaneous, 180 µg, Once weekly, 48 weeks

Other names: BMS-914143

Entecavir

Drug

Tablet, Oral, 0.5 mg, Once daily, 12 weeks initial monotherapy followed by 48 weeks of combination therapy with PegIFN lambda

Other names: Baraclude

Primary outcomes

  1. Part A: Proportion of subjects who achieve Hepatitis B e antigen (HBeAg) seroconversion

    Time frame: 24 weeks post-dosing (Week 72)

  2. Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events

    Time frame: Week 24

  3. Part A: Number and percent of subjects with serious adverse events (SAEs) and discontinuations due to adverse events

    Time frame: 24 weeks post-dosing (Week 72)

  4. Part B: Safety and tolerability of Lambda/ETV regimen as measured by the frequency of SAEs and discontinuations due to AEs

    Time frame: Up to 84 Weeks

Secondary outcomes

  1. Part A: Proportion of subjects who achieve an hepatitis B virus Deoxyribonucleic acid levels (HBV DNA) < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - High Pure System (HPS) assay

    Time frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192

  2. Part A: Mean change from baseline in log10 HBV DNA levels over time (Proportion of subjects with Alanine amino transferase (ALT) normalization (≤ 1 x upper limit of normal (ULN))

    Time frame: Baseline (Day 1), Weeks 24, 48, 72, 96, 120, 144, 168 and 192

  3. Part A: Proportion of subjects with ALT normalization (≤ 1 x ULN)

    Time frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192

  4. Part A: Hepatitis E antigen (HBeAg) loss

    Time frame: Weeks 24, 48, 72, 96, 120, 144, 168 and 192

  5. Part A: HBeAg seroconversion

    Time frame: Weeks 24, 48, 96, 120, 144, 168 and 192

  6. Part A: Mean change from baseline in log10 quantitative HBeAg levels over time

    Time frame: Baseline (Day 1), Weeks 24, 48, 96, 120, 144, 168 and 192

  7. Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities

    Time frame: Up to Week 24

  8. Part A: Number and percent of subjects with adverse events (AEs) or laboratory abnormalities

    Time frame: Up to Week 72

  9. Part A: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data

    Time frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

  10. Part A: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data

    Time frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

  11. Part A: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Pegylated interferon lambda (pegIFNλ) will be derived from serum concentration versus time data

    Time frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

  12. Part A: PK parameter serum concentration 168 hours post observed dose [Cmin] (C0 will be used as an estimate of Cmin if sample is not collected) of pegIFNλ will be derived from serum concentration versus time data

    Time frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

  13. Part A: PK parameter Area under the concentration-time curve in 1 dosing interval from time 0 to 168 hours post observed dose [AUC(TAU)] of pegIFNλ will be derived from serum concentration versus time data

    Time frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

  14. Part A: PK parameter Accumulation index (AI) ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (only conducted if data warrant) of pegIFNλ will be derived from serum concentration versus time data

    Time frame: Day 1 (including intense PK), Weeks 2, 4, 12 (including intense PK), 16, 24, 40, 48

  15. Part B: HBeAg seroconversion rate at 24 weeks off treatment

    Time frame: Week 84

  16. Part B: Antiviral activity of Lambda/ETV regimen, as determined by the proportion of subjects who achieve an HBV DNA < 50 IU/mL (approximately 300 copies/mL) using the Roche COBAS® TaqMan - HPS assay

    Time frame: Weeks 4, 8, 12, 24, 36, 60, and 84

  17. Part B: Mean change from baseline in HBV DNA over time in subjects treated with Lambda/ETV

    Time frame: Weeks 4, 8, 12, 24, 36, 60, and 84

  18. Part B: HBeAg loss and seroconversion in subjects treated with Lambda/ETV regimen

    Time frame: Weeks 12, 24, 36, 60 and 84

  19. Part B: HBeAg levels over time in subjects treated with Lambda/ETV regimen

    Time frame: Weeks 4, 8, 12, 24, 36, 60, and 84

  20. Part B: biochemical response rates in subjects treated with Lambda/ETV regimen

    Time frame: Weeks 4, 8, 12, 24, 36, 60, and 84

  21. Part B: Pharmacokinetic (PK) parameter Maximum observed concentration (Cmax) of Lambda/ETV regimen will be derived from serum concentration versus time data

    Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60

  22. Part B: Pharmacokinetic (PK) parameter Time of maximum observed concentration (Tmax) of Lambda/ETV regimen will be derived from serum concentration versus time data

    Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60

  23. Part B: Pharmacokinetic (PK) parameter Trough serum concentration pre-dose (C0) of Lambda/ETV regimen will be derived from serum concentration versus time data

    Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60

  24. Part B: PK parameter Area under the concentration-time curve in 1 dosing interval from time 0 to 168 hours post observed dose [AUC(TAU)] of Lambda/ETV regimen will be derived from serum concentration versus time data

    Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60

  25. Part B: PK parameter serum concentration 168 hours post observed dose [Cmin] (C0 will be used as an estimate of Cmin if sample is not collected) of Lambda/ETV regimen will be derived from serum concentration versus time data

    Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60

  26. Part B: PK parameter Accumulation index (AI) ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose (only conducted if data warrant) of Lambda/ETV regimen will be derived from serum concentration versus time data

    Time frame: Baseline (Day 1), Weeks 4, 12, 16, 24, 52, 60

  27. Part B: Rate of resistance to ETV during treatment with the Lambda/ETV regimen

    Time frame: Up to Week 84

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

Dose-Ranging Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Pegylated Interferon Lambda (BMS-914143) Monotherapy in Interferon-Naive Patients With Chronic Hepatitis B Virus Infection Who Are HBeAg-positive

Acronym: LIRA-B

Important dates

Study start
2010
Primary completion
2013
Study completion
2013
First posted
Sep 17, 2010
Registry last updated
Oct 9, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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