Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection

NCT03312023 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HP-00074723
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of therapy against chronic hepatitis B are to decrease the morbidity and mortality related to chronic HBV infection. Currently available antiviral therapy can suppress viral replication but only a small proportion attain functional cure, which is defined as HBV surface antigen-to-antibody seroconversion. Hepatitis B surface antigen (HBsAg) is a marker of persistent hepatitis B infection. It has been observed that patients who had both hepatitis B and hepatitis C, and who were treated for their hepatitis C with 12 weeks of ledipasvir/sofosbuvir for had a decline in HBsAg levels. This study hypothesizes that a similar decrease would be seen in mono-infected hepatitis B subjects over the course of 12 weeks treatment with ledipasvir/sofosbuvir.

Conditions

Hepatitis B

Keywords

Hepatitis B; HBsAg; Ledipasvir/Sofosbuvir; Hepatitis B treatment

Outcome Measures

Primary Outcomes (2)

• Change of Serum Hepatitis B Surface Antigen (HBsAg as Measured in log10 IU/mL) Level as an Indicator of Antiviral Activity of Ledipasvir and/or Sofosbuvir in Subjects With Chronic Hepatitis B From Baseline to End of 12 Weeks Treatment.

  Subjects with chronic hepatitis B will be give 12 weeks of ledipasvir and/or sofosbuvir and their HBsAg will be measured at baseline, on each visits during therapy, and at end of therapy (week 12). The change (decline) in HBsAg from baseline to end of the 12 week treatment will be compared.

  12 weeks

• Incidence of Adverse Events Leading to Permanent Discontinuation of Ledipasvir and/or Sofosbuvir Treatment in Subjects With Chronic Hepatitis B Infection.

  Number of subjects who discontinued study drug due to adverse event

  12 Weeks

Secondary Outcomes (1)

• Changes in Serum Hepatitis B Virus DNA Levels (HBV DNA as Measured in IU/mL) With Treatment of Ledipasvir and/or Sofosbuvir From Baseline to End of 12 Weeks of Treatment in Subjects With Chronic Hepatitis B Infection.

  12 weeks

Study Arms (4)

Group A (LDV/SOF for low replicative HBV)

EXPERIMENTAL

12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state.

Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]

Group B (LDV/SOF for viral suppressed HBV)

EXPERIMENTAL

12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed.

Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]

Group C (SOF for low replicative HBV)

EXPERIMENTAL

12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D.

Drug: Sofosbuvir 400 MG [Sovaldi]

Group D (LDV for low replicative HBV)

EXPERIMENTAL

12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C.

Drug: Ledipasvir 90 MG

Interventions

Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni] DRUG

1 pill once daily for 12 weeks for Group A

Also known as: Harvoni

Group A (LDV/SOF for low replicative HBV); Group B (LDV/SOF for viral suppressed HBV)

Sofosbuvir 400 MG [Sovaldi] DRUG

1 pill once daily for 12 weeks for Group C

Also known as: GS-7977

Group C (SOF for low replicative HBV)

Ledipasvir 90 MG DRUG

1 pill once daily for 12 weeks for Group D

Also known as: GS-5885

Group D (LDV for low replicative HBV)

Eligibility Criteria

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

You may qualify if:

• Participants in Groups A, C \& D (Chronic HBV, low replicative state not requiring treatment):
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 or older at screening
• Diagnosed with chronic hepatitis B infection defined as one of the following:
• HBsAg or HBV DNA positivity for at least 6 months
• Medical records indicating a chronic HBV infection
• HBeAg negative at screening
• HBV DNA \> lower level of quantitation (LLOQ)
• Quantitative HBsAg at least 10 IU/mL at screening
• Ability to take oral medication and be willing to adhere to the twelve week study drug regimen
• For females of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 30 days after the end of study drug administration
• For males of reproductive potential: usual practice of complete abstinence from sexual intercourse with a member of the opposite sex OR use of at least one form of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 14 days after the end of study drug administration
• Ability to communicate effectively with the study investigator and key staff
• Medical management provided by a primary care provider

You may not qualify if:

• Coinfection with hepatitis C, hepatitis D or human immunodeficiency virus (HIV)
• Pregnancy or lactation
• Known allergic reactions to sofosbuvir or ledipasvir
• Treatment with another investigational drug or other intervention within three months
• Evidence of cirrhosis or hepatic decompensation such as:
• Platelets less than 100,000 /mm3
• Albumin less than 3.5 g/dL
• INR greater than 1.7 or Prothrombin time of 1.5 times the upper limit of normal (ULN)
• Total bilirubin of 1.5 times the upper limit of normal
• FibroTest (or FibroSure®) of 0.75 or greater
• Abnormal hematological and biochemical parameters at screening including:
• White blood cell count less than 2500 cells/uL
• Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects)
• Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females
• AST or ALT of two times the upper limit of normal

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Gilead Sciences: collaborator

Study Sites (1)

Institute of Human Virology (IHV), University of Maryland Baltimore

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

ledipasvir; Sofosbuvir; Tablets; ledipasvir, sofosbuvir drug combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Joel V. Chua
• Organization: Institute of Human Virology, University of Maryland Baltimore

jchua@ihv.umaryland.edu

1-410-706-5704

Study Officials

• Joel V Chua, MD

  University of Maryland, College Park

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Ten potential subjects for Groups C and D will be randomized in a 1:1 fashion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Open-label Study, multi-arm

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 17, 2017
• Study Start: February 1, 2018
• Primary Completion: August 10, 2020
• Study Completion: June 30, 2021
• Last Updated: September 20, 2021
• Results First Posted: August 25, 2021

Record last verified: 2021-08

Locations

US (1)