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Crohn's DiseasePhase 1NCT02249078

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 3 Subcutaneous and 1 Intravenous Dose of E6011 in Subjects With Active Crohn's Disease

A Phase 1 study testing E6011 in people with Crohn's Disease, run by Eisai Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a multicenter, Phase 1b, randomized, double-blind, placebo-controlled, sequential-cohort, multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of 3 subcutaneous and 1 intravenous dose of E6011 in subjects with active Crohn's disease (CD). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Crohn's Disease
What is being tested?
E6011
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2014to Apr 2016
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects must meet all of the following criteria to be included in this study:
  • Male or female subjects age greater than or equal to 18 years old at the time of informed consent
  • Confirmed diagnosis of CD, with at least one documented lesion within the reach of a colonoscope (terminal ileal or ileo-colonic or colonic) from a previous colonoscopy, for a minimum duration of 6 months at the time of screening
  • Active CD with a CD activity index (CDAI) score greater than or equal to 220 and less than or equal to 450
  • Colonoscopic evidence of CD involvement with active inflammation of terminal ileum and/or colon at Screening (performed only in subjects who have otherwise met all of the inclusion and none of the exclusion criteria)
  • Inadequate response to, loss of response to, or intolerance of at least one of the following agents as defined below:
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  • Immunomodulators:
  • Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of oral azathioprine (AZA) (greater than or equal to 1.5 mg/kg) or 6-mercaptopurine (6-MP) mg/kg (greater than or equal to 0.75 mg/kg) OR
  • Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of methotrexate (MTX) (greater than or equal to 12.5 mg/week)
  • History of intolerance to at least 1 immunomodulator (including, but not limited to) nausea/vomiting, abdominal pain, pancreatitis, liver function test (LFT) abnormalities, lymphopenia, thiopurine methyltransferase (TPMT) genetic mutation, infection
  • Tumor Necrosis Factor (TNF)-alpha antagonists:
  • Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen of one of the following agents:
  • Infliximab: 5 mg/kg IV, 2 doses at least 2 weeks apart
  • Adalimumab: one 80 mg SC dose followed by one 40-mg dose at least 2 weeks apart
  • Certolizumab pegol: 400 mg SC dose, 2 doses at least 2 weeks apart OR
  • Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify)
  • History of intolerance to at least 1 TNF antagonist (including, but not limited to infusion-related reaction, demyelination, congestive heart failure, infection)
  • C-reactive protein greater than or equal to 5 mg/L at screening or fecal calprotectin greater than or equal to 250 ug/g
  • Females must not be breastfeeding or pregnant at Screening (as documented by a negative beta-human chorionic gonadotropin [B-hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  • Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 70 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 70 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 70 days after study drug discontinuation. All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
  • Provide written informed consent
  • Willing and able to comply with all aspects of the protocol

Who cannot join

  • Subjects who meet any of the following criteria will be excluded from this study:
  • Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal [other than CD], renal disease, active infection, vasculitides) that in the opinion of the investigator(s) could affect the patient's safety or interfere with the study assessments
  • Any neurologic abnormality at screening
  • A prolonged QT/QTc interval (QTc greater than 450 ms) as demonstrated by a repeated ECG at Screening
  • History of any severe allergy
  • Scheduled for surgery during planned participation in the study
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  • Previous ileo-colonic resections or presence of an ostomy
  • Presence of active fistulizing CD
  • Total parenteral nutrition (TPN) or enema for treating CD within 2 weeks before Screening
  • Treatment with adalimumab or certolizumab within 2 weeks before Screening
  • Treatment with infliximab within 4 weeks (or 8 weeks if subjects received 10 mg/kg) before Screening
  • Treatment with vedolizumab (in case of approval or off-label use) or any other monoclonal antibody within 8 weeks before starting the study treatment
  • History of treatment with natalizumab
  • Changes in dose of 5-aminosalicylic acid, 6-MP, MTX, and AZA therapy within 4 weeks of Screening
  • Doses of greater than 30 mg/day of prednisone or equivalent at Screening
  • Parenteral corticosteroids use within 4 weeks of Screening
  • Treatment with cyclosporine (oral or IV), tacrolimus hydrate (excluding eyedrops or skin cream), sirolimus, or mycophenolate mofetil within 8 weeks before Screening
  • Positive Clostridium difficile toxin test at Screening
  • Known to be human immunodeficiency virus (HIV) positive at Screening
  • History of tuberculosis or known current active tuberculosis
  • Positive results for Mycobacterium tuberculosis using an Interferon-Gamma Release Assay at Screening
  • Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
  • Use of live vaccine and immunoglobulin preparations within 12 weeks of screening
  • Cluster of differentiation-4 (CD4) positive cell count below 200/microliter (uL) or white blood cell count below 3,000/uL at screening
  • Any of the following laboratory abnormalities in tests conducted during Screening
  • Hemoglobin: less than 8.0 g/dL
  • Neutrophil count: less than 1,500/uL
  • Platelet count: less than 100,000/uL
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT): greater than 2.5 times the upper limit of standard reference values
  • Serum creatinine: greater than 1.5 mg/dL
  • Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years
  • History of drug or alcohol dependency or abuse within the 2 years prior to Screening
  • Current use of illegal recreational drugs
  • Currently enrolled in another clinical study or used any investigational drug or device within 28 days preceding informed consent

About this study

Official title: A Multicenter, Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Sequential-Cohort, Multiple-Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of 3 Subcutaneous and 1 Intravenous Dose of E6011 in Subjects With Active Crohn's Disease

This is a multicenter, Phase 1b, randomized, double-blind, placebo-controlled, sequential-cohort, multiple ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of 3 subcutaneous and 1 intravenous dose of E6011 in subjects with active Crohn's disease (CD). Thirty-two subjects will be randomized to one of 4 dose cohorts (8 per cohort) and will receive E6011 or placebo for 10 weeks. The first 3 cohorts will receive E6011 or placebo via subcutaneous injection and the last cohort will receive E6011 or placebo by intravenous injection. The ratio of E6011 to placebo within each cohort will be 3:1. The study has 2 phases: Prerandomization and Randomization.

Conditions
Crohn's Disease
Being tested
E6011, Placebo
Keywords
Crohn's Disease
Medical subject headings
Crohn Disease

What participants receive

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

  • E6011Drug

    E6011 solution for injection

  • PlaceboDrug

    Placebo 2-mL vial solution for injection

Study groups in NCT02249078
Study groupRoleWhat they receive
Cohort 1Experimental100 mg subcutaneous once every 2 weeks with initial double dose (200 mg total)
Receives: Drug: E6011
Cohort 2Experimental200 mg subcutaneous once every 2 weeks with initial double dose (400 mg total)
Receives: Drug: E6011
Cohort 3Experimental400 mg subcutaneous once every 2 weeks with initial double dose (800 mg total)
Receives: Drug: E6011
Cohort 4Experimental10 mg/kg IV at Day 1, Day 8, Day 15, and every 2 weeks thereafter
Receives: Drug: E6011
PlaceboPlacebo comparatorPlacebo 2-mL vial solution for injection
Receives: Drug: Placebo

What is being measured

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

  1. Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of the short-term safety and tolerability of E6011

    The short-term safety and tolerability of subcutaneous (SC) and intravenous (IV) doses of E6011 compared to placebo in subjects with active CD. Safety assessments will consist of monitoring and recording all AEs and SAEs; regulatory monitoring of hematology, blood chemistry, and urine values; periodic measurement vital signs and ECGs; and performance of physical examinations.

    Measured: Up to 3 years

Secondary outcomes (4)

  1. Concentration of E6011 measured over time in blood samples.

    Measured: Up to 3 years

  2. The number and percentage of participants with anti-E6011 antibodies detected in blood samples over time.

    Measured: Up to 3 years

  3. The number of screen positives, confirm positives, and relative anti-E6011 levels measured in blood samples from participants.

    Measured: Up to 3 years

  4. Change from baseline in the percentage of immunohistochemical staining for the CX3CR1+ protein in intestinal tissue over time.

    Measured: Up to 3 years

Timeline

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

  1. First posted25 Sep 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionMar 2016 (estimated)
  4. Study completionApr 2016 (estimated)

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02249078
Sponsor's protocol ID
E6011-A001-102
Status last verified
Nov 2015
First submitted
23 Sep 2014
Last updated
5 Nov 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E6011 in people with Crohn's Disease, run by Eisai Inc..

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 22 inclusion and 34 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: withdrawn, as of the sponsor's last update on 5 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 was withdrawn before enrolling participants, so there are no results.

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 with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of the short-term safety and tolerability of E6011 (time frame: Up to 3 years). 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 NCT02249078.

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 5 Nov 2015.

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