ThrombocytopeniaPhase 2NCT01355289
Chronic Hepatitis C Virus Related Thrombocytopenia to Evaluate the Effects of E5501
A Phase 2 study testing Avatrombopag, Pegylated interferon (PEG-IFN) and Telaprevir in people with Thrombocytopenia, run by Eisai Inc. at 2 sites in United States.
Trial summary
To evaluate the efficacy of E5501 by measuring platelet response in subjects with chronic hepatitis C virus (HCV)-related thrombocytopenia who require antiviral treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thrombocytopenia
- What is being tested?
- Avatrombopag, Pegylated interferon (PEG-IFN) and Telaprevir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2011to May 2014
- 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
- Males or females greater than or equal to 18 years of age
- Women of childbearing potential must agree to use a highly effective method of contraception for at least one menstrual cycle prior to starting study drug, throughout the entire study period, and for 30 days after the last dose of study drug
- Subjects with chronic HCV-related thrombocytopenia (defined as a platelet count greater than or equal to 20x10^9/L to 70x10^9/L) who require antiviral treatment
- Chronic HCV infection (defined as the presence of anti-HCV antibodies and detectable serum HCV RNA levels)
- Model for End-stage Liver disease score greater than or equal to 24
- Adequate renal function as evidenced by a calculated creatinine clearance greater than or equal to 50 mL/minute per the Cockcroft and Gault formula
Show all 33Show fewer
- Life expectancy greater than or equal to 3 months
- Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from participation in the study:
- Any history of arterial or venous thrombosis, including partial or complete thrombosis (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism), thrombosis (partial or complete) in the main portal vein and portal vein branches, and thrombosis of any part of the splenic-mesenteric system
- Any evidence of current portal vein thrombosis (PVT) as detected by Doppler sonography and portal vein flow rate less than 15 cm/second at Screening or within 30 days prior to Screening (revised per Amendment 02)
- Any known family history of hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency)
- Evidence of myocardial infarction in the last 6 months or uncompensated congestive heart failure (New York Heart Association Class III or IV)
- Co-infection with human immunodeficiency virus (HIV) or hepatitis B or acute hepatitis C
- Any prohibited concomitant medications or therapy that cannot be discontinued by Visit 1, e.g., subjects currently receiving interferon who cannot undergo a 4-week washout period prior to Screening, or subjects who receive blood products that affect platelet count within 1 week prior to Screening (revised per Amendment 02)
- Weekly alcohol intake greater than 21 units (168 g) [male] and greater than 14 units (112 g) [female]
- Any known medical condition, other than chronic liver disease, that can lead to thrombocytopenia
- History of hepatocellular carcinoma, metastatic liver cancer, or liver transplantation (revised per Amendment 01) (revised per Amendment 02)
- History of idiopathic thrombocytopenic Purpura (ITP)
- History of myelodysplastic syndrome
- History of pernicious anemia or subjects with vitamin B12 deficiency (defined as less than the lower limit of normal [LLN]) who have not had pernicious anemia excluded as a cause (Added per Amendment 02)
- Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that, in the opinion of the investigator, could affect the subject's safety or study conduct
- Subjects with a history of suicide attempts
- Subjects with a history of hospitalization for depression within the past 5 years
- Subjects with any current severe or poorly controlled psychiatric or seizure disorder
- Current use of recreational drugs
- Subjects who have participated in another investigational study within 30 days prior to Visit 1
- Subjects with hypersensitivity, intolerance, or allergy to E5501 or any anti-HCV therapies or their ingredients
- Any past or current (revised per Amendment 01) medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study
- Scheduled for surgery during the projected course of the study
- Subjects who have any medical conditions or diseases that would contraindicate treatment with anti-HCV therapy (added per Amendment 01)
- Subjects who are currently treated with proton pump inhibitors (PPIs) or H2-antagonist therapy but have not been receiving a stable dose for at least 6 weeks prior to randomization or have not completed these therapies more than 2 weeks prior to randomization (added per Amendment 01)
- Fasting gastrin-17 blood levels exceeding 1.5 times the upper limit of normal (ULN) at Screening (including subjects on PPIs or H2 antagonists) (revised per Amendment 02)
- Subjects with a history of gastric atrophy (added per Amendment 02)
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Metropolitan Research
Fairfax, Virginia, 22031
Health Care Consultants
Los Angeles, California
About this study
Official title: A Phase II, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study, With an Open-Label Extension, to Evaluate the Efficacy, Safety, and Pharmacokinetics of E5501 in Subjects With Chronic Hepatitis C Virus Related Thrombocytopenia Who Are Potential Candidates for Antiviral Treatment
To evaluate the efficacy of E5501 by measuring platelet response in subjects with chronic hepatitis C virus (HCV)-related thrombocytopenia who require antiviral treatment.
Read the detailed description
This study had three phases: Prerandomization (Screening), Randomization (Core Study), and Open-Label Extension (OLE). The Randomization Phase included Treatment Periods A1 and A2 and a Follow-up Period (for those participants not continuing into the OLE phase). The OLE Phase included Treatment Periods B1, B2, and B3 (depending on when a participant entered the OLE), and a Follow-up Period. Participants may have been followed for sustained viral response, if appropriate. In the Core Study (randomization phase) participants were randomized (in a 1:1:1:1 ratio) to receive one of four treatments (placebo or avatrombopag [10mg, 20mg, and 30mg] for up to 21 days. Participants who successfully completed Treatment Period A1, (platelet count >=100x10^9/L) initiated antiviral treatment with pegylated interferon (PEG-IFN) alpha-2a and progressed to Treatment Period A2. Participants with a platelet count >=150x10^9/L initiated antiviral treatment and progressed into Treatment Period B2, study drug was interrupted then eventually restarted at 10 mg daily once their platelet counts returned to acceptable levels. Those who were not considered successful after 21 days in Treatment Phase A1 were withdrawn from the Core Study (Part A) and were eligible to enter the OLE at Treatment Period B1. Participants who chose to not enter the OLE entered into the Follow-up Phase. At the end of Treatment Period A2, eligible participants could enter the OLE at Treatment Period B3. In the OLE Phase, participants entering into Open-label Treatment Period B1 began once-daily treatment with avatrombopag at a dose of 20 mg without titration for up to 21 days. Once the participant's platelet counts were sufficient, they entered Treatment Period B2. Participant's eligible to enter into Treatment Period B2 received avatrombopag and antiviral treatment for 13 weeks. Participants who successfully completed Treatment Period A2 or B2 could continue on antiviral treatment for up to a maximum of 48 weeks (including the 13 weeks in Treatment Periods A2 or B2) and open-label avatrombopag, at the investigator's discretion. In Treatment Period B3, the dose of avatrombopag was allowed to be titrated up or down in accordance with the participant's platelet count response, within the range of a minimum of 5 mg and a maximum of 50 mg. In the Follow-up Period, participants were seen at either a single 30-day follow-up visit or followed for the full 30 days after the last dose of avatrombopag.
- Conditions
- Thrombocytopenia
- Being tested
- Avatrombopag, Placebo, Pegylated interferon (PEG-IFN), Telaprevir, Ribavirin
- Keywords
- Chronic Hepatitis C related
- Medical subject headings
- Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvatrombopagDrug
Also called E5501, Avatrombopag maleate
PlaceboDrug
Pegylated interferon (PEG-IFN)Drug
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor.
TelaprevirDrug
Also called Incivek, Incivo
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor
RibavirinDrug
Also called Virazole, Rebetol, Copegus, Ribasphere
Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor
| Study group | Role | What they receive |
|---|---|---|
| Placebo (Core Study) | Placebo comparator | Placebo, will be administered orally, once daily for up to 21 days. Receives: Drug: Placebo |
| Avatrombopag 10 mg (Core Study) | Active comparator | Avatrombopag 10 mg, will be administered orally, once daily, preferably with food for up to 21 days. Receives: Drug: Avatrombopag |
| Avatrombopag 20 mg (Core Study) | Active comparator | Avatrombopag 20 mg, will be administered orally, once daily, preferably with food for up to 21 days. Receives: Drug: Avatrombopag; Drug: Pegylated interferon (PEG-IFN); Drug: Telaprevir; Drug: Ribavirin |
| Avatrombopag 30 mg (Core Study) | Active comparator | Avatrombopag 30 mg, will be administered orally, once daily, preferably with food for up to 21 days. Receives: Drug: Avatrombopag |
| Avatrombopag (Open-Label Extension) | Experimental | Avatrombopag will be initiated at a dose of 20 mg, once daily in the open-label extension (OLE) period. The avatrombopag dose will be titrated up or down in accordance with the participant's individual response, within the range of a minimum of 5 mg and a maximum of 50 mg for up to 48 weeks. Receives: Drug: Avatrombopag; Drug: Pegylated interferon (PEG-IFN); Drug: Telaprevir; Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study
A responder was defined as a participant having a platelet count of greater than or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater than 20 x 10^9/L to less than or equal to 70 x 10^9/L.
Measured: Baseline to Day 21
Secondary outcomes (3)
Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study
Missing platelet counts were imputed using last observation carried forward (LOCF) approach for subjects who achieved platelet response at prior visits.
Measured: Day 7 and Day 14
Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study
Blood draws were taken to monitor platelet counts.
Measured: Baseline to Day 21
Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study
Blood draws were taken to monitor platelet counts during the first 21 days of study treatment. When a platelet count of greater than or equal to 100 X 10^9/L was attained, antiviral treatment was initiated.
Measured: Baseline to Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2011 (estimated)
- Study startNov 2011
- Primary completionFeb 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alireza Manhuchehri, Study director, Eisai Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01355289
- Sponsor's protocol ID
- E5501-G000-203
- Status last verified
- Jan 2018
- First submitted
- 16 May 2011
- Last updated
- 22 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Multicenter, Placebo-Controlled, Double-Blind, Parallel-Group Study, With an Open-Label Extension, to Evaluate the Efficacy, Safety, and Pharmacokinetics of E5501 in Subjects With Chronic Hepatitis C Virus Related Thrombocytopenia Who Are Potential Candidates for Antiviral Treatment
- ClinicalTrials.gov ID
- NCT01355289
- Acronym / sponsor ID
- E5501-G000-203
- Conditions
- Thrombocytopenia
- Keywords
- Chronic Hepatitis C related
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 18 May 2011 (estimated)
- Results
- Posted 22 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy of E5501 by measuring platelet response in subjects with chronic hepatitis C virus (HCV)-related thrombocytopenia who require antiviral treatment.
Detailed description
This study had three phases: Prerandomization (Screening), Randomization (Core Study), and Open-Label Extension (OLE). The Randomization Phase included Treatment Periods A1 and A2 and a Follow-up Period (for those participants not continuing into the OLE phase). The OLE Phase included Treatment Periods B1, B2, and B3 (depending on when a participant entered the OLE), and a Follow-up Period. Participants may have been followed for sustained viral response, if appropriate. In the Core Study (randomization phase) participants were randomized (in a 1:1:1:1 ratio) to receive one of four treatments (placebo or avatrombopag [10mg, 20mg, and 30mg] for up to 21 days. Participants who successfully completed Treatment Period A1, (platelet count >=100x10^9/L) initiated antiviral treatment with pegylated interferon (PEG-IFN) alpha-2a and progressed to Treatment Period A2. Participants with a platelet count >=150x10^9/L initiated antiviral treatment and progressed into Treatment Period B2, study drug was interrupted then eventually restarted at 10 mg daily once their platelet counts returned to acceptable levels. Those who were not considered successful after 21 days in Treatment Phase A1 were withdrawn from the Core Study (Part A) and were eligible to enter the OLE at Treatment Period B1. Participants who chose to not enter the OLE entered into the Follow-up Phase. At the end of Treatment Period A2, eligible participants could enter the OLE at Treatment Period B3. In the OLE Phase, participants entering into Open-label Treatment Period B1 began once-daily treatment with avatrombopag at a dose of 20 mg without titration for up to 21 days. Once the participant's platelet counts were sufficient, they entered Treatment Period B2. Participant's eligible to enter into Treatment Period B2 received avatrombopag and antiviral treatment for 13 weeks. Participants who successfully completed Treatment Period A2 or B2 could continue on antiviral treatment for up to a maximum of 48 weeks (including the 13 weeks in Treatment Periods A2 or B2) and open-label avatrombopag, at the investigator's discretion. In Treatment Period B3, the dose of avatrombopag was allowed to be titrated up or down in accordance with the participant's platelet count response, within the range of a minimum of 5 mg and a maximum of 50 mg. In the Follow-up Period, participants were seen at either a single 30-day follow-up visit or followed for the full 30 days after the last dose of avatrombopag.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Placebo (Core Study) | Placebo comparator | Drug: PlaceboPlacebo, will be administered orally, once daily for up to 21 days. |
| Avatrombopag 10 mg (Core Study) | Active comparator | Drug: AvatrombopagAvatrombopag 10 mg, will be administered orally, once daily, preferably with food for up to 21 days. |
| Avatrombopag 20 mg (Core Study) | Active comparator | Drug: Avatrombopag, Drug: Pegylated interferon (PEG-IFN), Drug: Telaprevir, Drug: RibavirinAvatrombopag 20 mg, will be administered orally, once daily, preferably with food for up to 21 days. |
| Avatrombopag 30 mg (Core Study) | Active comparator | Drug: AvatrombopagAvatrombopag 30 mg, will be administered orally, once daily, preferably with food for up to 21 days. |
| Avatrombopag (Open-Label Extension) | Experimental | Drug: Avatrombopag, Drug: Pegylated interferon (PEG-IFN), Drug: Telaprevir, Drug: RibavirinAvatrombopag will be initiated at a dose of 20 mg, once daily in the open-label extension (OLE) period. The avatrombopag dose will be titrated up or down in accordance with the participant's individual response, within the range of a minimum of 5 mg and a maximum of 50 mg for up to 48 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Males or females greater than or equal to 18 years of age
- Women of childbearing potential must agree to use a highly effective method of contraception for at least one menstrual cycle prior to starting study drug, throughout the entire study period, and for 30 days after the last dose of study drug
- Subjects with chronic HCV-related thrombocytopenia (defined as a platelet count greater than or equal to 20x10^9/L to 70x10^9/L) who require antiviral treatment
- Chronic HCV infection (defined as the presence of anti-HCV antibodies and detectable serum HCV RNA levels)
- Model for End-stage Liver disease score greater than or equal to 24
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AvatrombopagAlso: E5501, Avatrombopag maleate | Drug | Avatrombopag (Open-Label Extension), Avatrombopag 10 mg (Core Study), Avatrombopag 20 mg (Core Study), Avatrombopag 30 mg (Core Study) |
| Placebo | Drug | Placebo (Core Study) |
| Pegylated interferon (PEG-IFN)Participants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor. | Drug | Avatrombopag (Open-Label Extension), Avatrombopag 20 mg (Core Study) |
| TelaprevirAlso: Incivek, IncivoParticipants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor | Drug | Avatrombopag (Open-Label Extension), Avatrombopag 20 mg (Core Study) |
| RibavirinAlso: Virazole, Rebetol, Copegus, RibasphereParticipants in Treatment Periods A2, B2, and B3 are to receive antiviral treatment PEG-IFN, ribavirin, or telaprevir. Provided by the sponsor | Drug | Avatrombopag (Open-Label Extension), Avatrombopag 20 mg (Core Study) |
Primary outcome
Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study
Time frame: Baseline to Day 21
A responder was defined as a participant having a platelet count of greater than or equal to 100x10^9/L by Day 21 starting from an average baseline platelet count of greater than 20 x 10^9/L to less than or equal to 70 x 10^9/L.
3 secondary outcomes
Change From Baseline of Local Platelet Count by Visit During Treatment Period A1 of Core Study
Time frame: Day 7 and Day 14
Number of Participants Who Achieved Platelet Count Greater Than 30 X 10^9/L From Baseline to Day 21 During Treatment Period A1 of Core Study
Time frame: Baseline to Day 21
Number of Participants Who Initiated Antiviral Treatment by Day 21 of Period A1 of Core Study
Time frame: Baseline to Day 21
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Thrombocytopenia
RecruitingObservational study
A Study in Children and, Adults With Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Treated With Adzynma
Thrombotic Thrombocytopenic Purpura (TTP)
RecruitingPhase 3
rhTPO for Thrombocytopenia in Chronic Liver Disease Patients Undergoing Elective Invasive Procedures.
Thrombocytopenia Associated With Chronic Liver Disease
RecruitingPhase 2
A Study to Assess the Tolerability of Ianalumab (VAY736) With Investigator's Choice Thrombopoietin Receptor Agonist (IC TPO-RA) in Patients With Primary Immune Thrombocytopenia (ITP)
Primary Immune Thrombocytopenia (ITP), Primary Evans Syndrome (ES)
Enrolling by invitationObservational study
Screening for Hematology Branch Protocols
Hematologic Disease and Disorders, Donors
RecruitingPhase 1/2
A Study of Pirtobrutinib in Participants With Immune Thrombocytopenia
Immune Thrombocytopenia (ITP)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alireza Manhuchehri study director
Eisai Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Avatrombopag, Pegylated interferon (PEG-IFN) and Telaprevir in people with Thrombocytopenia, run by Eisai Inc. at 2 sites 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 0 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 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 22 Feb 2018). 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?
Number of Participants Who Achieved Platelet Response (Greater Than or Equal to 100 x 10^9/L) by Day 21 of Treatment Period A1 of Core Study (time frame: Baseline to Day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Feb 2018.