A Study of Lirentelimab (AK002) in Patients With Active Eosinophilic Esophagitis

NCT ID: NCT04322708

Last Updated: 2024-01-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

277 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-06

Study Completion Date

2022-01-18

Brief Summary

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This is a Phase 2/3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002) given monthly for 6 doses in adult and adolescent patients with active eosinophilic esophagitis. Subjects who complete the randomized, double-blind, placebo-controlled treatment may have the option to receive 6 doses of open-label lirentelimab (AK002) through the OLE Period of the study.

Detailed Description

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Conditions

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Eosinophilic Esophagitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Subjects in this arm will receive 6 monthly doses of placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo

1 mg/kg of lirentelimab (AK002)

Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) (1mg/kg).

Group Type EXPERIMENTAL

lirentelimab (AK002)

Intervention Type DRUG

Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.

3 mg/kg of lirentelimab (AK002)

Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002): A first dose of 1 mg/kg, followed by 5 monthly doses of 3 mg/kg.

Group Type EXPERIMENTAL

lirentelimab (AK002)

Intervention Type DRUG

Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.

Interventions

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Placebo

Placebo

Intervention Type OTHER

lirentelimab (AK002)

Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female aged ≥12 and ≤80 years at the time of signing ICF.
2. Confirmed diagnosis of EoE and esophageal intraepithelial eosinophilic infiltration of ≥15 eosinophils/hpf in 1 hpf from a biopsy collected during the Screening EGD without any other cause for the esophageal eosinophilia.
3. History (by patient report) of an average of ≥2 episodes of dysphagia with intake of solid foods per week during the 4 weeks prior to Screening.
4. Subjects must have failed or not be adequately controlled on standard of care treatments for EoE symptoms, which could include PPI, systemic or topical corticosteroids, and/or diet, among others.
5. If on an allowed treatment for EoE, stable dose for at least 4 weeks prior to Screening and willingness to continue that dose for the study duration.
6. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
7. Able and willing to comply with all study procedures.
8. Female subjects must be either post-menopausal for at least 1 year with FSH level \>30 mIU/mL at Screening or surgically sterile (tubal ligation,hysterectomy, or bilateral oophorectomy) for at least 3 months, or if of childbearing potential, have a negative pregnancy test and agree to use dual methods of contraception, or abstain from sexual activity from screening until the end of the study, or for 120 days following the last dose of study drug, whichever is longer. Male subjects with female partners of childbearing potential must agree to use a highly effective method of contraception from Screening until the end of the study or for 120 days following the last dose of study drug,whichever is longer. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant at any time during study participation.

Exclusion Criteria

1. Concomitant EG, EoD, or eosinophilic colitis (EC).
2. EG and/or EoD (≥30 eosinophils/hpf in 5 hpf in the stomach and/or ≥30 eosinophils/hpf in 3 hpf in the duodenum) as determined by central histology assessment of biopsies collected during the Screening EGD.
3. Causes of esophageal eosinophilia other than EoE or one the following: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, or peripheral blood absolute eosinophil count of \>1500 eosinophils/μL.
4. History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
5. Any esophageal stricture unable to be passed with a standard diagnostic 9 mm to 10 mm upper endoscope or any critical esophageal stricture that requires dilation during screening.
6. History of bleeding disorders or esophageal varices.
7. History of malignancy; except carcinoma in situ, early stage prostate cancer, or non-melanoma skin cancers. However, cancers that have been in remission for more than 5 years and are considered cured, can be enrolled (with the exception of breast cancer). All history of malignancy (including diagnosis, dates, and compliance with cancer screening recommendations) must be documented and certified by the Investigator, along with the statement that in their clinical judgment the tissue eosinophilia is attributable to EGID, rather than recurrence of malignancy.
8. Active Helicobacter pylori infection (as determined by central histology staining of the biopsy collected during the Screening EGD), unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
9. Positive Ova and Parasite (O\&P) test at Screening, seropositive for Strongyloides stercoralis at Screening, and/or treatment for a clinically significant helminthic parasitic infection within 6 months of Screening.
10. Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.
11. Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
12. Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.
13. Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.
14. Use of any biologics or medications that may interfere with the study, such as immunosuppressive or immunomodulatory drugs including azathioprine, JAK inhibitors, 6-mercaptopurine, methotrexate, cyclosporine, tacrolimus, anti-TNF, anti-IL-4 receptor, e.g., dupilumab), anti-IL-5 (e.g., mepolizumab), anti-IL-5 receptor (e.g., benralizumab), anti-IL-13 (e.g., lebrikizumab), anti-IgE (e.g., omalizumab), within 12 weeks prior to Screening.
15. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to administration of study drug or 90 days or 5 half-lives, whichever is longer, for biologic products.
16. Vaccination with live attenuated vaccines ≤30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected ≤5 half-lives (≤4 months) following study drug administration.
17. Treatment with chemotherapy or radiotherapy in the preceding 6 months.
18. Presence of abnormal laboratory values considered by the Investigator to be clinically significant.
19. Any disease, condition (medical or surgical), or cardiac abnormality, which in the opinion of the Investigator, would place the subject at increased risk.
20. Known history of alcohol, drug, or other substance abuse or dependence.
21. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
22. Any other reason that in the opinion of the Investigator or Medical Monitor makes the patient unsuitable for enrollment.
Minimum Eligible Age

12 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Allakos Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Craig Paterson, MD

Role: STUDY_DIRECTOR

Allakos Inc.

Locations

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Allakos Investigational Site

Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Gilbert, Arizona, United States

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Phoenix, Arizona, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Little Rock, Arkansas, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Oakland, California, United States

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Santa Monica, California, United States

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Tustin, California, United States

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Ventura, California, United States

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Walnut Creek, California, United States

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Aurora, Colorado, United States

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Centennial, Colorado, United States

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Brandon, Florida, United States

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Edgewater, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Columbus, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Lexington, Kentucky, United States

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Crowley, Louisiana, United States

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Chevy Chase, Maryland, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Troy, Michigan, United States

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Kansas City, Missouri, United States

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Kalispell, Montana, United States

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Las Vegas, Nevada, United States

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Reno, Nevada, United States

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Great Neck, New York, United States

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New York, New York, United States

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Asheville, North Carolina, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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High Point, North Carolina, United States

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Rocky Mount, North Carolina, United States

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Akron, Ohio, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Mentor, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Danville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Greenville, South Carolina, United States

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Chattanooga, Tennessee, United States

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Hixson, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Garland, Texas, United States

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San Antonio, Texas, United States

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Ogden, Utah, United States

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Riverton, Utah, United States

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Salt Lake City, Utah, United States

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Sandy City, Utah, United States

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Leesburg, Virginia, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Adelaide, South Australia, Australia

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Elizabeth Vale, South Australia, Australia

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Box Hill, Victoria, Australia

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Prahran, Victoria, Australia

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Amsterdam, North Holland, Netherlands

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Countries

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United States Australia Netherlands

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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AK002-014

Identifier Type: -

Identifier Source: org_study_id

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