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Hepatitis BPhase 2APOSTLENCT03312023

Ledipasvir/Sofosbuvir for Hepatitis B Virus Infection

A Phase 2 study testing Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni], Sofosbuvir 400 MG [Sovaldi] and Ledipasvir 90 MG in people with Hepatitis B, run by University of Maryland, Baltimore at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis B
What is being tested?
Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni], Sofosbuvir 400 MG [Sovaldi] and Ledipasvir 90 MG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
1 Feb 2018to 30 Jun 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Ability to store medications at a room temperature of less than 86 degrees Fahrenheit
  • Not on antiviral therapy or requiring treatment for HBV during screening
  • Participants in Group B (Chronic HBV, virally suppressed):
  • 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
  • Receiving oral anti-HBV medications (either tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, or a combination of no more than 2 of these agents) for at least three months prior to enrollment
  • HBV DNA ˂ lower level of quantitation (LLOQ) at screening and for at least three months prior
  • 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
  • Ability to store medications at a room temperature of less than 86 degrees Fahrenheit

Who cannot join

  • 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
Show all 29Show fewer
  • 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
  • Estimated GFR less than 50 mL/min
  • Glycosylated hemoglobin (HbA1c) greater than 8.5%
  • Current or prior history of any of the following:
  • Immunodeficiency disorders or autoimmune disease (e.g. Systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel diseases, sarcoidosis, psoriasis of greater than mild severity)
  • Severe pulmonary disorders, significant cardiac diseases
  • Gastrointestinal disorder with post-operative condition that could interfere with the absorption of the study drugs
  • Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent
  • Any malignancy diagnosed within 5 years (not including recent localized treatment of squamous or non-invasive basal cell skin cancer; cervical carcinoma in situ appropriately treated prior to screening)
  • Solid organ transplantation
  • Poor venous access
  • Screening ECG with clinically significant findings
  • Evidence of HCC (e.g., α fetoprotein > 50ng/mL or radiologic evidence)
  • Clinically significant illicit drug or alcohol abuse within 12 months of screening. Subjects on methadone maintenance treatment or prescribed opioid may be included.
  • Use of amiodarone within 90 days of enrollment; or carbamazepine, phenytoin, phenobarbital, oxcarbazepine, rifabutin, rifampin, rifapentine, St. John's wort, rosuvastatin, or interferon within 30 days of enrollment or expected use of these prohibited drugs during study participation. Use of or expected need of proton-pump inhibitors more than 20 mg omeprazole equivalent or H2 receptor antagonist more than 40 mg famotidine BID equivalent within 7 days of enrollment.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Baltimore, Maryland, 21201

Other trials in United States

About this study

Official title: A Phase II Open-Label Study of Ledipasvir/Sofosbuvir for 12 Weeks in Subjects With Hepatitis B Virus Infection

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
Being tested
Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni], Sofosbuvir 400 MG [Sovaldi], Ledipasvir 90 MG
Keywords
Hepatitis B, HBsAg, Ledipasvir/Sofosbuvir, Hepatitis B treatment
Medical subject headings
Hepatitis B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called Harvoni

    1 pill once daily for 12 weeks for Group A

  • Sofosbuvir 400 MG [Sovaldi]Drug

    Also called GS-7977

    1 pill once daily for 12 weeks for Group C

  • Ledipasvir 90 MGDrug

    Also called GS-5885

    1 pill once daily for 12 weeks for Group D

Study groups in NCT03312023
Study groupRoleWhat they receive
Group A (LDV/SOF for low replicative HBV)Experimental12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B in low replicative state.
Receives: Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]
Group B (LDV/SOF for viral suppressed HBV)Experimental12 week treatment with ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis B, virally suppressed.
Receives: Drug: Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni]
Group C (SOF for low replicative HBV)Experimental12 weeks treatment with sofosbuvir (Sovaldi) for chronic hepatitis B in low replicative state. Randomized 1:1 with Group D.
Receives: Drug: Sofosbuvir 400 MG [Sovaldi]
Group D (LDV for low replicative HBV)Experimental12 weeks treatment with ledipasvir for chronic hepatitis B in low replicative state. Randomized 1:1 with Group C.
Receives: Drug: Ledipasvir 90 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 weeks

  2. 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

    Measured: 12 Weeks

Secondary outcomes (1)

  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.

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

    Note: Group B (virally suppressed HBV subjects) - all had HBV DNA below the limit of detection; Hence, mean change was 0.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2017
  2. Study start1 Feb 2018
  3. Primary completion10 Aug 2020
  4. Study completion30 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-label Study, multi-arm
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03312023
Sponsor's protocol ID
HP-00074723
Acronym
APOSTLE
Status last verified
Aug 2021
First submitted
29 Sep 2017
Last updated
20 Sep 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ledipasvir 90 MG / Sofosbuvir 400 MG Oral Tablet [Harvoni], Sofosbuvir 400 MG [Sovaldi] and Ledipasvir 90 MG in people with Hepatitis B, run by University of Maryland, Baltimore at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03312023.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2021; AzTrials last refreshed its copy on 2 Nov 2026.

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