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

NCT02249078 | Withdrawn Phase 1

• 1 other identifier: E6011-A001-102
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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). 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

Keywords

Crohn's Disease

Outcome Measures

Primary Outcomes (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.

  Up to 3 years

Secondary Outcomes (4)

• Concentration of E6011 measured over time in blood samples.

  Up to 3 years

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

  Up to 3 years

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

  Up to 3 years

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

  Up to 3 years

Study Arms (5)

Cohort 1

EXPERIMENTAL

100 mg subcutaneous once every 2 weeks with initial double dose (200 mg total)

Drug: E6011

Cohort 2

EXPERIMENTAL

200 mg subcutaneous once every 2 weeks with initial double dose (400 mg total)

Drug: E6011

Cohort 3

EXPERIMENTAL

400 mg subcutaneous once every 2 weeks with initial double dose (800 mg total)

Drug: E6011

Cohort 4

EXPERIMENTAL

10 mg/kg IV at Day 1, Day 8, Day 15, and every 2 weeks thereafter

Drug: E6011

Placebo

PLACEBO COMPARATOR

Placebo 2-mL vial solution for injection

Drug: Placebo

Interventions

E6011 DRUG

E6011 solution for injection

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Placebo DRUG

Placebo 2-mL vial solution for injection

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Inadequate response to, loss of response to, or intolerance of at least one of the following agents as defined below:
• 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).

Sponsors & Collaborators

• Eisai Inc.: lead

MeSH Terms

Conditions

Crohn Disease

Interventions

quetmolimab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: September 25, 2014
• Study Start: December 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: November 5, 2015

Record last verified: 2015-11