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

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AK002 in Patients With Moderately to Severely Active Eosinophilic Duodenitis Who Have an Inadequate Response With, Lost Response to, or Were Intolerant to Standard Therapies

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 adult patients with active eosinophilic duodenitis. 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.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Gastroenteritis; Eosinophilic Duodenitis
• Intervention / Treatment: Other: Placebo; Drug: AK002

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Allakos Investigational Site
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Allakos Investigational Site
  • California
    • Chula Vista, California, United States, 91910
      • Allakos Investigational Site
    • Lomita, California, United States, 90717
      • Allakos Investigational Site
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Allakos Investigational Site
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Allakos Investigational Site
    • Hamden, Connecticut, United States, 06518
      • 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
    • Kissimmee, Florida, United States, 34741
      • Allakos Investigational Site
    • Lakewood Ranch, Florida, United States, 34211
      • Allakos Investigational Site
    • New Port Richey, Florida, United States, 34653
      • Allakos Investigational Site
    • Ponte Vedra, Florida, United States, 32081
      • Allakos Investigational Site
  • Louisiana
    • Crowley, Louisiana, United States, 70526
      • Allakos Investigational Site
  • Nevada
    • Reno, Nevada, United States, 89511
      • Allakos Investigational Site
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Allakos Investigational Site
  • New York
    • Great Neck, New York, United States, 11023
      • Allakos Investigational Site
  • North Carolina
    • Concord, North Carolina, United States, 28027
      • Allakos Investigational Site
    • Durham, North Carolina, United States, 27710
      • Allakos Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Allakos Investigational Site
    • Cincinnati, Ohio, United States, 45231
      • Allakos Investigational Site
    • Dayton, Ohio, United States, 45415
      • Allakos Investigational Site
    • Mentor, Ohio, United States, 44094
      • Allakos Investigational Site
  • South Carolina
    • Greenwood, South Carolina, United States, 29646
      • Allakos Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Allakos Investigational Site
    • Hermitage, Tennessee, United States, 37076
      • Allakos Investigational Site
    • Hixson, Tennessee, United States, 37343
      • Allakos Investigational Site
  • Texas
    • Austin, Texas, United States, 78745
      • Allakos Investigational Site
    • Cedar Park, Texas, United States, 78613
      • Allakos Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Allakos Investigational Site
    • Lubbock, Texas, United States, 79410
      • Allakos Investigational Site
    • San Antonio, Texas, United States, 78229
      • Allakos Investigational Site
    • Southlake, Texas, United States, 76092
      • Allakos Investigational Site
    • Webster, Texas, United States, 77598
      • Allakos Investigational Site
  • Utah
    • Ogden, Utah, United States, 84405
      • Allakos Investigational Site
    • Salt Lake City, Utah, United States, 84132
      • Allakos Investigational Site
    • Sandy, Utah, United States, 84092
      • Allakos Investigational Site
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Allakos Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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 3 hpf in the duodenum, as determined by central histology assessment of biopsies collected during the screening EGD + colonoscopy, without any other significant cause for the eosinophilia.
4. Completion of at least 4 daily PRO questionnaires per week for a minimum of 3 weeks during screening.
5. A weekly average score of abdominal pain, nausea, or diarrhea ≥3 on the PRO questionnaire (score from 0-10) for at least 2 weeks of screening and a weekly average TSS of ≥10 for at least 2 weeks of screening.
6. Inadequate or loss of response to, or intolerant to standard therapies for EoD symptoms, which could include PPI, antihistamines, systemic or topical corticosteroids, and/or diet, among others.
7. If patient is on pre-existing dietary restrictions, willingness to maintain dietary restrictions throughout the study.
8. Willing and able to comply with all study procedures and visit schedule including follow-up visits.
9. 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.

Exclusion Criteria:

1. Use of systemic or topical corticosteroids exceeding the equivalent of 10 mg/day prednisone within 4 weeks prior to the screening visit.
2. Baseline endoscopic biopsy with ≥30 eosinophils/hpf in 5 hpf in the gastric mucosa as determined by central histology assessment of biopsies collected during the screening EGD.
3. Change in the dose of corticosteroids (systemic or topical), PPI, leukotrienes, or diet therapy within 4 weeks prior to the screening visit.
4. Treatment with any immunosuppressive or immunomodulatory drugs that may interfere with the study within 12 weeks prior to the screening visit.
5. Prior exposure to AK002 or known hypersensitivity to any constituent of the study drug.
6. Active Helicobacter pylori infection, unless treated and confirmed to be negative by repeat EGD (for baseline eosinophil count) prior to randomization and symptoms remain consistent.
7. History of inflammatory bowel disease, other chronic inflammatory diseases in the colon (with the exception of eosinophilic colitis), celiac disease, achalasia, or esophageal surgery.
8. History of bleeding disorders and/or esophageal varices.
9. Other causes of duodenal eosinophilia or eosinophilic granulomatosis with polyangiitis.
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, patients with cancers that have been in remission for more than 5 years and are considered cured can be enrolled.
14. Treatment for a clinically significant helminthic parasitic infection within 6 months of screening.
15. Positive helminthic infection on Ova and Parasite (O&P) test.
16. Seropositive for Strongyloides stercoralis at screening.
17. Seropositive for HIV or hepatitis at screening, except for vaccinated patients or patients with past but resolved hepatitis, at screening.
18. 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. This exclusion criterion does not apply to all types and formulations of vaccines (including live attenuated vaccines) authorized by FDA or other regulatory authority for the prevention of COVID-19, which may be administered before, during, or after the study.
19. 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).
20. Known history of alcohol, drug, or other substance abuse or dependence that is considered by the Investigator to be ongoing and clinically significant.
21. 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
Experimental: 3.0 mg/kg of Lirentelimab (AK002); Subjects in this arm will receive 6 monthly doses of lirentelimab (AK002) at 3 mg/kg.	Drug: AK002; Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1(IgG1) monoclonal antibody directed against Siglec-8.; Other Names: Lirentelimab
Placebo Comparator: Placebo; Subjects in this arm will receive 6 monthly doses of placebo at 3 mg/kg.	Other: Placebo; Placebo

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 <=15 cells/HPF in 3 duodenal HPFs	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
Percent Change in Tissue Eosinophils From Baseline to Week 24	Tissue eosinophil count obtained in biopsy specimens from the duodenum using esophago-gastro-duodenoscopy (EGD)	Baseline to Week 24
Subjects Achieving Eosinophils Count ≤1 Cell/Hpf in 3 Highest Duodenal Hpf at Week 24	Tissue eosinophil count obtained in biopsy specimens from the duodenum using esophago-gastro-duodenoscopy (EGD)	At Week 24
Number of Treatment Responders	Treatment responders defined by >30% improvement in TSS and eosinophil count ≤15 cells per hpf in 3 duodenal hpf	At Weeks 23-24 and Week 24, Respectively
Subjects Who Achive ≥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): May 20, 2021
• Primary Completion (Actual): June 14, 2022
• Study Completion (Actual): January 9, 2023

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 23, 2021

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: Eosinophil; Eosinophilic gastrointestinal disorders; EGID; Eosinophilic; EoD
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Hypersensitivity; Esophageal Diseases; Esophagitis; Duodenal Diseases; Leukocyte Disorders; Eosinophilia; Enteritis; Gastroenteritis; Eosinophilic Esophagitis; Duodenitis
• Other Study ID Numbers: AK002-021

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
• product manufactured in and exported from the U.S.: No