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

NCT04322708 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AK002-014
• Study Type: interventional
• Target: 277
• Locations: 3 countries
• Sites: 78

Brief Summary

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.

Conditions

Eosinophilic Esophagitis

Keywords

EoE; Eosinophil; Esophagitis

Outcome Measures

Primary Outcomes (2)

• Proportion of Subjects Who Achieve a Peak Esophageal Intraepithelial Count of ≤6 Eosinophils/Hpf at Week 24

  Esophageal intraepithelial eosinophil count obtained by esophageal endoscopy with biopsies.

  At Week 24

• Change in Dysphagia Symptom Questionnaire (DSQ) Score From Baseline to Weeks 23-24.

  The DSQ is used to measure the frequency and intensity of dysphagia. DSQ scores can range from 0 to 84, with a lower score indicating less-frequent or less-severe dysphagia.

  Baseline to Weeks 23-24

Secondary Outcomes (8)

• Percent Change in Peak Esophageal Intraepithelial Eosinophil Count From Baseline to Week 24

  Baseline to Week 24

• Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤1 Eosinophil/Hpf at Week 24

  At Week 24

• Subjects Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/Hpf at Week 24

  At Week 24

• Number of Treatment Responders

  At Weeks 23-24 and Week 24, Respectively

• Subjects Who Achieve >50% Reduction in DSQ Score From Baseline to Weeks 23-24

  Weeks 23-24

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

1 mg/kg of lirentelimab (AK002)

EXPERIMENTAL

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

Drug: lirentelimab (AK002)

3 mg/kg of lirentelimab (AK002)

EXPERIMENTAL

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.

Drug: lirentelimab (AK002)

Interventions

Placebo OTHER

Placebo

Placebo

lirentelimab (AK002) DRUG

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

1 mg/kg of lirentelimab (AK002); 3 mg/kg of lirentelimab (AK002)

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥12 and ≤80 years at the time of signing ICF.
• 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.
• 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.
• 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.
• 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.
• If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study, as much as possible.
• Able and willing to comply with all study procedures.
• 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.

You may not qualify if:

• Concomitant EG, EoD, or eosinophilic colitis (EC).
• 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.
• 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.
• History of inflammatory bowel disease, celiac disease, achalasia, and/or esophageal surgery.
• 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.
• History of bleeding disorders or esophageal varices.
• 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.
• 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.
• 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.
• Seropositive for HIV or hepatitis at Screening, except for vaccinated patients or patients with a history of hepatitis that has since resolved.
• Prior exposure to AK002 or hypersensitivity to any constituent of AK002.
• Change in dose of inhaled corticosteroids, nasal corticosteroids, PPI, and/or diet therapy within 4 weeks prior to Screening.
• Use of oral corticosteroids (swallowed topical or systemic corticosteroids) within 8 weeks prior to Screening.
• 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.
• 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.

Sponsors & Collaborators

• Allakos Inc.: lead

Study Sites (78)

Allakos Investigational Site

Birmingham, Alabama, 35209, United States

Location

Allakos Investigational Site

Huntsville, Alabama, 38801, United States

Location

Allakos Investigational Site

Gilbert, Arizona, 85234, United States

Location

Allakos Investigational Site

Phoenix, Arizona, 85016, United States

Location

Allakos Investigational Site

Phoenix, Arizona, 85021, United States

Location

Allakos Investigational Site

Scottsdale, Arizona, 85251, United States

Location

Allakos Investigational Site

Little Rock, Arkansas, 72205, United States

Location

Allakos Investigational Site

La Jolla, California, 92037, United States

Location

Allakos Investigational Site

Los Angeles, California, 90025, United States

Location

Allakos Investigational Site

Oakland, California, 94612, United States

Location

Allakos Investigational Site

Santa Monica, California, 90404, United States

Location

Allakos Investigational Site

Tustin, California, 92780, United States

Location

Allakos Investigational Site

Ventura, California, 93003, United States

Location

Allakos Investigational Site

Walnut Creek, California, 94598, United States

Location

Allakos Investigational Site

Aurora, Colorado, 80045, United States

Location

Allakos Investigational Site

Centennial, Colorado, 80112, United States

Location

Allakos Investigational Site

Brandon, Florida, 33511, United States

Location

Allakos Investigational Site

Edgewater, Florida, 32132, United States

Location

Allakos Investigational Site

Jacksonville, Florida, 32256, United States

Location

Allakos Investigational Site

Miami, Florida, 33176, United States

Location

Allakos Investigational Site

Orlando, Florida, 32803, United States

Location

Allakos Investigational Site

Orlando, Florida, 32806, United States

Location

Allakos Investigational Site

Tampa, Florida, 33603, United States

Location

Allakos Investigational Site

Tampa, Florida, 33615, United States

Location

Allakos Investigational Site

Atlanta, Georgia, 30342, United States

Location

Allakos Investigational Site

Columbus, Georgia, 31904, United States

Location

Allakos Investigational Site

Chicago, Illinois, 60611, United States

Location

Allakos Investigational Site

Indianapolis, Indiana, 46202, United States

Location

Allakos Investigational Site

Iowa City, Iowa, 52242, United States

Location

Allakos Investigational Site

Lexington, Kentucky, 40503, United States

Location

Allakos Investigational Site

Crowley, Louisiana, 70526, United States

Location

Allakos Investigational Site

Chevy Chase, Maryland, 20815, United States

Location

Allakos Investigational Site

Boston, Massachusetts, 02111, United States

Location

Allakos Investigational Site

Boston, Massachusetts, 02115, United States

Location

Allakos Investigational Site

Boston, Massachusetts, 02215, United States

Location

Allakos Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

Allakos Investigational Site

Troy, Michigan, 48098, United States

Location

Allakos Investigational Site

Kansas City, Missouri, 64108, United States

Location

Allakos Investigational Site

Kalispell, Montana, 59901, United States

Location

Allakos Investigational Site

Las Vegas, Nevada, 89106, United States

Location

Allakos Investigational Site

Reno, Nevada, 89511, United States

Location

Allakos Investigational Site

Great Neck, New York, 11021, United States

Location

Allakos Investigational Site

New York, New York, 10029, United States

Location

Allakos Investigational Site

Asheville, North Carolina, 28801, United States

Location

Allakos Investigational Site

Chapel Hill, North Carolina, 27599, United States

Location

Allakos Investigational Site

Charlotte, North Carolina, 28210, United States

Location

Allakos Investigational Site

Charlotte, North Carolina, 28277, United States

Location

Allakos Investigational Site

Durham, North Carolina, 27710, United States

Location

Allakos Investigational Site

High Point, North Carolina, 27262, United States

Location

Allakos Investigational Site

Rocky Mount, North Carolina, 27804, United States

Location

Allakos Investigational Site

Akron, Ohio, 44302, United States

Location

Allakos Investigational Site

Cincinnati, Ohio, 45229, United States

Location

Allakos Investigational Site

Cincinnati, Ohio, 45231, United States

Location

Allakos Investigational Site

Cleveland, Ohio, 44106, United States

Location

Allakos Investigational Site

Dayton, Ohio, 45415, United States

Location

Allakos Investigational Site

Mentor, Ohio, 44060, United States

Location

Allakos Investigational Site

Oklahoma City, Oklahoma, 73112, United States

Location

Allakos Investigational Site

Danville, Pennsylvania, 17822, United States

Location

Allakos Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Allakos Investigational Site

Greenville, South Carolina, 29615, United States

Location

Allakos Investigational Site

Chattanooga, Tennessee, 37421, United States

Location

Allakos Investigational Site

Hixson, Tennessee, 37343, United States

Location

Allakos Investigational Site

Nashville, Tennessee, 37212, United States

Location

Allakos Investigational Site

Austin, Texas, 78704, United States

Location

Allakos Investigational Site

Garland, Texas, 75044, United States

Location

Allakos Investigational Site

San Antonio, Texas, 78229, United States

Location

Allakos Investigational Site

Ogden, Utah, 84405, United States

Location

Allakos Investigational Site

Riverton, Utah, 84065, United States

Location

Allakos Investigational Site

Salt Lake City, Utah, 84132, United States

Location

Allakos Investigational Site

Sandy City, Utah, 84092, United States

Location

Allakos Investigational Site

Leesburg, Virginia, 20176, United States

Location

Allakos Investigational Site

Seattle, Washington, 98105, United States

Location

Allakos Investigational Site

Seattle, Washington, 98115, United States

Location

Allakos Investigational Site

Adelaide, South Australia, 5000, Australia

Location

Allakos Investigational Site

Elizabeth Vale, South Australia, 5112, Australia

Location

Allakos Investigational Site

Box Hill, Victoria, 3128, Australia

Location

Allakos Investigational Site

Prahran, Victoria, 3181, Australia

Location

Allakos Investigational Site

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Eosinophilic Esophagitis; Esophagitis

Interventions

AK002

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Medical Information
• Organization: Allakos

medinfo@allakos.com

650-597-5002

Study Officials

• Craig Paterson, MD

  Allakos Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2020
• First Posted: March 26, 2020
• Study Start: July 6, 2020
• Primary Completion: June 4, 2021
• Study Completion: January 18, 2022
• Last Updated: January 2, 2024
• Results First Posted: January 2, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); US (73); NL (1)