A Study to Assess AK002 in Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis) (ENIGMA 2)

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Gastritis and/or Eosinophilic Duodenitis (Formerly Referred to as Eosinophilic Gastroenteritis)

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

Study Overview

• Status: Completed
• Conditions: Eosinophilic Gastritis; Eosinophilic Duodenitis
• Intervention / Treatment: Other: Placebo; Drug: lirentelimab (AK002)

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Allakos Investigational Site
    • Huntsville, Alabama, United States, 38801
      • Allakos Investigational Site
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Allakos Investigational Site
    • Phoenix, Arizona, United States, 85021
      • Allakos Investigational Site
    • Scottsdale, Arizona, United States, 85259
      • Allakos Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Allakos Investigational Site
  • California
    • Chula Vista, California, United States, 91910
      • Allakos Investigational Site
    • La Jolla, California, United States, 92037
      • Allakos Investigational Site
    • Murrieta, California, United States, 92563
      • Allakos Investigational Site
    • Oakland, California, United States, 94612
      • Allakos Investigational Site
    • Santa Monica, California, United States, 90404
      • Allakos Investigational Site
    • Tustin, California, United States, 92780
      • Allakos Investigational Site
    • Ventura, California, United States, 93003
      • Allakos Investigational Site
    • Walnut Creek, California, United States, 94598
      • Allakos Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Allakos Investigational Site
    • Colorado Springs, Colorado, United States, 80907
      • Allakos Investigational Site
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Allakos Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • Allakos Investigational Site
    • Edgewater, Florida, United States, 32132
      • Allakos Investigational Site
    • Jacksonville, Florida, United States, 32256
      • Allakos Investigational Site
    • Miami, Florida, United States, 33176
      • Allakos Investigational Site
    • New Port Richey, Florida, United States, 34653
      • Allakos Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Allakos Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Allakos Investigational Site
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Allakos Investigational Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Allakos Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Allakos Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Allakos Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Allakos Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Allakos Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Allakos Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Allakos Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Allakos Investigational Site
    • Reno, Nevada, United States, 89511
      • Allakos Investigational Site
  • New York
    • Great Neck, New York, United States, 11021
      • Allakos Investigational Site
    • New York, New York, United States, 10029
      • Allakos Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Allakos Investigational Site
    • Charlotte, North Carolina, United States, 28210
      • Allakos Investigational Site
    • Durham, North Carolina, United States, 27710
      • Allakos Investigational Site
    • Rocky Mount, North Carolina, United States, 27804
      • Allakos Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Allakos Investigational Site
    • Cincinnati, Ohio, United States, 45229
      • Allakos Investigational Site
    • Cleveland, Ohio, United States, 44106
      • Allakos Investigational Site
    • Dayton, Ohio, United States, 45415
      • Allakos Investigational Site
    • Mentor, Ohio, United States, 44060
      • Allakos Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Allakos Investigational Site
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Allakos Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Allakos Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Allakos Investigational Site
    • Hixson, Tennessee, United States, 37343
      • Allakos Investigational Site
    • Kingsport, Tennessee, United States, 37663
      • Allakos Investigational Site
    • Nashville, Tennessee, United States, 37212
      • Allakos Investigational Site
  • Texas
    • Austin, Texas, United States, 78704
      • Allakos Investigational Site
    • Houston, Texas, United States, 77070
      • Allakos Investigational Site
  • Utah
    • Ogden, Utah, United States, 84405
      • Allakos Investigational Site
    • Riverton, Utah, United States, 84065
      • Allakos Investigational Site
    • Salt Lake City, Utah, United States, 84132
      • Allakos Investigational Site
    • Sandy, Utah, United States, 84092
      • Allakos Investigational Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Allakos Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202
      • Allakos Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Provide written informed consent.
2. Male or female aged ≥18 and ≤80 years at the time of signing the informed consent for entry.
3. 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.
4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
5. 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.
6. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.
7. Willing and able to comply with all study procedures and visit schedule including follow-up visits.
8. 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.

Key Exclusion Criteria:

1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day of prednisone within 4 weeks prior to the screening visit.
2. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
3. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
4. Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
5. Active Helicobacter pylori infection, unless treated and confirmed to be negative prior to randomization and symptoms remain consistent.
6. History of inflammatory bowel disease, celiac disease, achalasia, or esophageal surgery.
7. History of bleeding disorders and/or esophageal varices.
8. Other causes of gastric and/or duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis (EGPA).
9. Confirmed diagnosis of Hypereosinophilic Syndrome (HES).
10. Women who are pregnant, breastfeeding, or planning to become pregnant while participating in the study.
11. Presence of an abnormal laboratory value considered to be clinically significant by the Investigator.
12. Any disease, condition (medical or surgical), or cardiac abnormality, which, in the opinion of the Investigator, would place the patient at increased risk.
13. 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).
14. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
15. Positive Ova and Parasite (O&P) test and/or seropositive for Strongyloides stercoralis.
16. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration.
17. Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved hepatitis, at screening.
18. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products).
19. Known history of alcohol, drug, or other substance abuse or dependence, considered by the Investigator to be ongoing and clinically significant.
20. Any other reason that in the opinion of the Investigator or the Medical Monitor makes the patient unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: 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.	Drug: lirentelimab (AK002); Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tissue Eosinophils From Baseline to Week 24	Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro-duodenoscopy (EGD)	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	Tissue eosinophil count obtained in biopsy specimens from the stomach and/or duodenum using esophago-gastro-duodenoscopy (EGD)	At Week 24
Number of Treatment Responders	Treatment responders defined by >30% improvement in TSS at Weeks 23-24 and eosinophil count ≤4 cells/hpf in 5 gastric hpf and/or eosinophil count ≤15 cells/hpf in 3 duodenal hpf at Week 24	Weeks 23-24 and at Week 24, respectively
Subjects Who Achieve ≥50% Reduction in 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.	At Weeks 23-24
Subjects Who Achieve ≥70% Reduction in 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.	At Weeks 23-24
Percent Change in Weekly TSS Over Time Using MMRM	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 Week 24

Collaborators and Investigators

• Sponsor: Allakos Inc.
• Investigators: Study Director: Craig Paterson, MD, Allakos Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Actual): November 29, 2021
• Study Completion (Actual): January 12, 2022

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Eosinophilic Gastritis; Eosinophilic Gastroenteritis; Eosinophil; EG; EGE; Eosinophilic gastrointestinal disorders; EGID; Eosinophilic; Eosinophilic Duodenitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Hypersensitivity; Esophageal Diseases; Esophagitis; Duodenal Diseases; Leukocyte Disorders; Gastritis; Gastroenteritis; Eosinophilic Esophagitis; Enteritis; Eosinophilia; Duodenitis
• Other Study ID Numbers: AK002-016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No