A Study to Assess AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)

NCT04322604 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: AK002-016
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 60

Brief Summary

This is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of lirentelimab (AK002), given monthly for 6 doses, in patients with moderately to severely active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (formerly referred to as Eosinophilic Gastroenteritis) who have an inadequate response with, lost response to, or were intolerant to standard therapies

Conditions

Eosinophilic Gastritis; Eosinophilic Duodenitis

Keywords

Eosinophil; Eosinophilic; Eosinophilic gastrointestinal disorders; EGID; EG; EGE; Eosinophilic Gastritis; Eosinophilic Gastroenteritis; Eosinophilic Duodenitis

Outcome Measures

Primary Outcomes (2)

• Proportion of Tissue Eosinophil Responders at Week 24

  A tissue eosinophil responder is defined as mean eosinophil count ≤4 cells/HPF in 5 gastric HPFs for EG only patients, ≤15 cells/HPF in 3 duodenal HPFs for EoD only patients, and ≤4 cells/HPF in 5 gastric HPFs and ≤15 cells/HPF in 3 duodenal HPFs for EG+EoD patients.

  At Week 24

• Change in PRO Total Symptom Score (TSS) From Baseline to Weeks 23-24

  The PRO Total Symptom Score (TSS) is a patient reported outcome (PRO) questionnaire comprises the following 6 symptoms: Abdominal pain intensity, Nausea intensity, Fullness before meal intensity, Loss of appetite intensity, Bloating intensity, and Abdominal cramping intensity. TSS scores can range from 0 to 60, with a lower score indicating less-severe symptoms.

  Baseline to Weeks 23 - 24

Secondary Outcomes (6)

• Change in Tissue Eosinophils From Baseline to Week 24

  Baseline to Week 24

• Subjects Achieving Mean Eosinophil Count ≤1 Cell/Hpf in 5 Highest Gastric Hpf and/or Mean Eosinophil Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24

  At Week 24

• Number of Treatment Responders

  Weeks 23-24 and at Week 24, respectively

• Subjects Who Achieve ≥50% Reduction in TSS From Baseline to Weeks 23-24

  At Weeks 23-24

• Subjects Who Achieve ≥70% Reduction in TSS From Baseline to Weeks 23-24

  At Weeks 23-24

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

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

lirentelimab (AK002) DRUG

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

3 mg/kg of lirentelimab (AK002)

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent.
• Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry.
• Baseline endoscopic biopsy with ≥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.
• Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
• Patients with inadequate or loss of response to, or who were intolerant to standard therapies for EG/EoD symptoms, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
• If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.
• Willing and able to comply with all study procedures and visit schedule including follow-up visits.
• Female patients 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 patients 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 (e.g., missed or later menstrual period) at any time during study participation.

You may not qualify if:

• Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
• Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
• Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
• Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
• Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
• History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
• History of bleeding disorders and/or esophageal varices.
• Other causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
• Confirmed diagnosis of Hypereosinophilic Syndrome (HES).
• Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
• Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
• Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk.
• 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).
• Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
• Positive Ova and Parasite (O\&P) test and/or seropositive for Strongyloides stercoralis.

Sponsors & Collaborators

• Allakos Inc.: lead

Study Sites (60)

Allakos Investigational Site

Birmingham, Alabama, 35209, United States

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Allakos Investigational Site

Huntsville, Alabama, 38801, United States

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Allakos Investigational Site

Gilbert, Arizona, 85234, United States

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Allakos Investigational Site

Phoenix, Arizona, 85021, United States

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Scottsdale, Arizona, 85259, United States

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Little Rock, Arkansas, 72205, United States

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Allakos Investigational Site

Chula Vista, California, 91910, United States

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Allakos Investigational Site

La Jolla, California, 92037, United States

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Allakos Investigational Site

Murrieta, California, 92563, United States

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Allakos Investigational Site

Oakland, California, 94612, United States

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Allakos Investigational Site

Santa Monica, California, 90404, United States

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Allakos Investigational Site

Tustin, California, 92780, United States

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Ventura, California, 93003, United States

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Allakos Investigational Site

Walnut Creek, California, 94598, United States

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Aurora, Colorado, 80045, United States

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Colorado Springs, Colorado, 80907, United States

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Bristol, Connecticut, 06010, United States

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Brandon, Florida, 33511, United States

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Allakos Investigational Site

Edgewater, Florida, 32132, United States

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Jacksonville, Florida, 32256, United States

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Miami, Florida, 33176, United States

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New Port Richey, Florida, 34653, United States

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Atlanta, Georgia, 30342, United States

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Allakos Investigational Site

Chicago, Illinois, 60611, United States

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Allakos Investigational Site

Crowley, Louisiana, 70526, United States

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Allakos Investigational Site

Chevy Chase, Maryland, 20815, United States

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Allakos Investigational Site

Boston, Massachusetts, 02111, United States

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Allakos Investigational Site

Boston, Massachusetts, 02115, United States

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Allakos Investigational Site

Boston, Massachusetts, 02215, United States

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Allakos Investigational Site

Ann Arbor, Michigan, 48109, United States

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Rochester, Minnesota, 55905, United States

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Kansas City, Missouri, 64108, United States

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Las Vegas, Nevada, 89106, United States

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Reno, Nevada, 89511, United States

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Great Neck, New York, 11021, United States

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New York, New York, 10029, United States

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Chapel Hill, North Carolina, 27599, United States

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Allakos Investigational Site

Charlotte, North Carolina, 28210, United States

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Durham, North Carolina, 27710, United States

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Allakos Investigational Site

Rocky Mount, North Carolina, 27804, United States

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Cincinnati, Ohio, 45229, United States

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Allakos Investigational Site

Cincinnati, Ohio, 45231, United States

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Allakos Investigational Site

Cleveland, Ohio, 44106, United States

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Dayton, Ohio, 45415, United States

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Mentor, Ohio, 44060, United States

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Oklahoma City, Oklahoma, 73112, United States

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Danville, Pennsylvania, 17822, United States

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Philadelphia, Pennsylvania, 19104, United States

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Chattanooga, Tennessee, 37421, United States

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Allakos Investigational Site

Hixson, Tennessee, 37343, United States

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Allakos Investigational Site

Kingsport, Tennessee, 37663, United States

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Allakos Investigational Site

Nashville, Tennessee, 37212, United States

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Allakos Investigational Site

Austin, Texas, 78704, United States

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Allakos Investigational Site

Houston, Texas, 77070, United States

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Allakos Investigational Site

Ogden, Utah, 84405, United States

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Allakos Investigational Site

Riverton, Utah, 84065, United States

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Allakos Investigational Site

Salt Lake City, Utah, 84132, United States

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Allakos Investigational Site

Sandy City, Utah, 84092, United States

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Allakos Investigational Site

Fairfax, Virginia, 22031, United States

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Allakos Investigational Site

Spokane, Washington, 99202, United States

Location

MeSH Terms

Conditions

Eosinophilic enteropathy; Eosinophilic Esophagitis

Interventions

AK002

Condition Hierarchy (Ancestors)

Esophagitis; 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 3
• 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: June 18, 2020
• Primary Completion: November 29, 2021
• Study Completion: January 12, 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

US (60)