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Chronic HBV Infection (HBeAg Negative)Phase 2NCT02233075

REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection

A Phase 2 study testing REP 2139-Ca + Pegasys (TM) in people with Chronic HBV Infection (HBeAg Negative), run by Replicor Inc. at 1 site in Moldova.

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

REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients and to act synergistically with immunotherapeutic agents such as pegylated interferon-alpha 2a or thymosin… Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Chronic HBV Infection (HBeAg Negative)
What is being tested?
REP 2139-Ca + Pegasys (TM)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteMoldova
Study dates
Sep 2014to May 2017
Phase
Phase 2
Are there results?
None posted in the registry

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 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Age between 18 and 55 years
  • HBsAg > 1000 IU / ml
  • HDAg+
  • HDV RNA +
  • No detectable antibodies to HIV, HCV or CMV.
  • Non cirrhotic
Show all 9Show fewer
  • Willingness to utilize adequate contraception while being treated with REP 213-Ca and for 6 months following the end of treatment
  • Adequate venous access allowing weekly intravenous therapies and blood tests
  • Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 25 kg/m2

Who cannot join

  • Evidence of cardiovascular disease
  • Evidence of autoimmune hepatitis
  • Presence of Wilson's disease
  • Presence of severe NAFLD
  • Evidence of any other co-existent liver disease
  • ANA (anti-nuclear antibody) positive
Show all 26Show fewer
  • Fibroscan and Fibromax showing evidence of advanced cirrhosis.
  • Any history of ascites, hepatic encephalopathy or variceal hemorrhage
  • Body weight > 100 kg
  • Platelet count < 90,000, PMN count < 1,500 or HCT < 33%
  • Evidence of significant heavy metal load in whole blood.
  • AFP > 100 ng/ml or the presence of a hepatic mass suggestive of HCC
  • Bilirubin above the normal range
  • ALT > 5x ULN
  • Creatinine > 1.5 mg/dl
  • Serum albumin < 35 mg/ml
  • The presence of diabetes (whether controlled or uncontrolled)
  • Another serious medical disorder
  • A serious psychiatric disorder
  • Evidence of hypertension
  • A history of alcohol abuse within the last year
  • The use of illicit drugs within the past two years
  • Inability to provide informed consent
  • Inability or unwillingness to provide weekly blood samples
  • Poor venous access making IV infusion too difficult
  • Patient not willing to come every week to receive therapy

Trial locations and contacts

1 site in 1 country.

Moldova1 site

  • Infectious Clinical Hospital ( n.a. Toma Ciorba)

    Chisinau, 2004

Other trials in Moldova

About this study

Official title: A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection

REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients and to act synergistically with immunotherapeutic agents such as pegylated interferon-alpha 2a or thymosin alpha-1 to restore host immunological control of HBV infection.

HBsAg is an essential component of the hepatitis D virus (HDV), therefore the direct action of REP 2139-Ca in removing serum HBsAg and its synergistic effect with pegylated interferon-alpha 2a is expected to have a significant antiviral effect against HDV infection.

Read more

This study will examine the safety and efficacy of REP 2139-Ca therapy when used in combination with pegylated interferon alpha-2a in patients with HBV / HDV co-infection.

The primary hypothesis to be tested is that this combined dosing regimen is safe and well tolerated in patients with HBV / HDV co-infection which will be assessed by examining the number of patients with adverse events (including reported symptoms and laboratory abnormalities).

The secondary hypothesis to be tested is that this combined dosing regimen will have an antiviral effect against HBV / HDV co-infection in these patients which will be assessed by examining the following outcomes:

  1. The number of patients with reductions in serum HBsAg.
  2. The number of patients with reductions in serum HDAg and HDV RNA
  3. The number of patients that experience a sustained antiviral response after treatment is stopped (reductions in serum HBV DNA and HDV RNA).

The secondary hypothesis to be tested is that this combination approach can have an effective

Read the detailed description

Nucleic acid polymers (NAPs) utilize the sequence independent properties of phosphorothioated oligonucleotides to target apolipoprotein interactions involved in the formation of HBV subviral particles (SVPs) which are comprised mainly of the hepatitis B surface antigen protein (HBsAg). The effect of NAPs is to block the formation of SVPs inside infected hepatocytes which prevents their secretion. As SVPs account for > 99.99% of HBsAg in the blood, NAPs are an effective approach for clearing HBsAg from the serum of HBV infected patient.

Previous clinical trials have demonstrated that treatment with the NAP REP 2139 results in the rapid and effective clearance of HBsAg from the blood. This HBsAg removal has the immediate effect of unmasking the underlying, pre-existing anti-HBsAg (anti-HBs) response, allowing clearance of HBV virus from the blood.

HBsAg has important immunosuppressive effects in HBV infection which have been shown to block both adaptive and innate immune processes. Removal of HBsAg from the blood of patients removes this immunosuppressive effect.

Thus, an important additional effect of removal of HBsAg from the blood is to greatly enhance the effect of immunotherapeutic agents like pegylated interferon alpha-2a or thymosin alpha-1 to stimulate recovery of complete immune control of HBV infection.

HDV superinfection can only occur in patients with HBV infection because HDV requires the HBsAg protein for its assembly. Therefore, it is expected that the removal of serum HBsAg (from HBV SVPs) and unmasking of the anticipated, pre-existing anti-HBsAg response by REP 2139 will result in the clearance of HBV and HDV from the blood. Furthermore, the enhanced effect of immunotherapy in the absence of serum HBsAg has the potential to provide a durable control of both HBV and HDV infection that will persist after treatment.

Being tested
REP 2139-Ca + Pegasys (TM)

What participants receive

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

  • REP 2139-Ca + Pegasys (TM)Drug

    Also called Pegasys(TM) = pegylated interferon alpha-2a

    15 weeks of REP 2139-Ca (500mg QW IV) followed by: 15 weeks of REP 2139-Ca (250mg QW IV) + Pegasys(TM) (180 ug QW SC) followed by: 33 weeks of Pegasys(TM) (180 ug QW SC)

Study groups in NCT02233075
Study groupRoleWhat they receive
REP 2139-Ca + Pegasys (TM)ExperimentalREP 2139-Ca 500 mg QW for 15 weeks followed by REP 2139-Ca 250mg QW + Pegasys(TM) 180ug QW for 15 weeks followed by Pegasys(TM) 180ug QW for 33 weeks.
Receives: Drug: REP 2139-Ca + Pegasys (TM)

What is being measured

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

  1. Number of patients experiencing a treatment-related adverse event.

    Will examine the hypothesis that combined REP 2139-Ca / Pegasys(TM) treatment is safe and well tolerated in patients with HBV / HDV co-infection

    Measured: Every week for 63 weeks.

Secondary outcomes (3)

  1. Number of patients with reduction of serum HBsAg.

    Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection.

    Measured: Every two weeks for 63 weeks (treatment duration) + 24 weeks (follow-up)

  2. Number of patients with reduced serum HDV antigen / HDV RNA

    Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection.

    Measured: Every two weeks for 63 weeks (treatment duration) + 24 weeks followup

  3. Number of patients with controlled HBV / HDV infection following treatment

    Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection.

    Measured: 24 weeks follow up (after completion of 63 weeks of treatment)

Timeline

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

  1. First posted8 Sep 2014 (estimated)
  2. Study startSep 2014
  3. Primary completionNov 2016
  4. Study completionMay 2017

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02233075
Sponsor's protocol ID
REP 301
Status last verified
Feb 2017
First submitted
1 Sep 2014
Last updated
28 Sep 2017
Results posted
No
Data monitoring committee
No

Publications

  • Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers inhibit duck hepatitis B virus infection in vitro. Antimicrob Agents Chemother. 2013 Nov;57(11):5291-8. doi: 10.1128/AAC.01003-13. Epub 2013 Aug 12.

    PubMed 23939902

  • Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers prevent the establishment of duck hepatitis B virus infection in vivo. Antimicrob Agents Chemother. 2013 Nov;57(11):5299-306. doi: 10.1128/AAC.01005-13. Epub 2013 Aug 12.

    PubMed 23939904

  • Bazinet M, Pantea V, Cebotarescu V, Cojuhari L, Jimbei P, Anderson M, Gersch J, Holzmayer V, Elsner C, Krawczyk A, Kuhns MC, Cloherty G, Dittmer U, Vaillant A. Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139-Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection. Hepatol Commun. 2020 Nov 13;5(2):189-202. doi: 10.1002/hep4.1633. eCollection 2021 Feb.

    PubMed 33553968

  • Bazinet M, Pantea V, Cebotarescu V, Cojuhari L, Jimbei P, Albrecht J, Schmid P, Le Gal F, Gordien E, Krawczyk A, Mijocevic H, Karimzadeh H, Roggendorf M, Vaillant A. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):877-889. doi: 10.1016/S2468-1253(17)30288-1. Epub 2017 Sep 28.

    PubMed 28964701

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing REP 2139-Ca + Pegasys (TM) in people with Chronic HBV Infection (HBeAg Negative), run by Replicor Inc. at 1 site in Moldova.

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 9 inclusion and 26 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 28 Sep 2017. 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 Moldova. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of patients experiencing a treatment-related adverse event. (time frame: Every week for 63 weeks.). 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 NCT02233075, which also lists 4 linked publications.

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 28 Sep 2017.

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