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

Eosinophilic Gastritis Clinical Trial

— ENIGMA 2  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04322604
• Other study ID #: AK002-016
• Status: Completed
• Phase: Phase 3
• Start date: June 18, 2020
• Est. completion date: January 12, 2022

Study information

• Verified date: December 2023
• Source: Allakos Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: January 12, 2022
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duodenitis
• Enteritis
• Eosinophilia
• Eosinophilic Duodenitis
• Eosinophilic Esophagitis
• Eosinophilic Gastritis
• Gastritis
• Gastroenteritis

Intervention

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

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Allakos Investigational Site	Ann Arbor	Michigan
United States	Allakos Investigational Site	Atlanta	Georgia
United States	Allakos Investigational Site	Aurora	Colorado
United States	Allakos Investigational Site	Austin	Texas
United States	Allakos Investigational Site	Birmingham	Alabama
United States	Allakos Investigational Site	Boston	Massachusetts
United States	Allakos Investigational Site	Boston	Massachusetts
United States	Allakos Investigational Site	Boston	Massachusetts
United States	Allakos Investigational Site	Brandon	Florida
United States	Allakos Investigational Site	Bristol	Connecticut
United States	Allakos Investigational Site	Chapel Hill	North Carolina
United States	Allakos Investigational Site	Charlotte	North Carolina
United States	Allakos Investigational Site	Chattanooga	Tennessee
United States	Allakos Investigational Site	Chevy Chase	Maryland
United States	Allakos Investigational Site	Chicago	Illinois
United States	Allakos Investigational Site	Chula Vista	California
United States	Allakos Investigational Site	Cincinnati	Ohio
United States	Allakos Investigational Site	Cincinnati	Ohio
United States	Allakos Investigational Site	Cleveland	Ohio
United States	Allakos Investigational Site	Colorado Springs	Colorado
United States	Allakos Investigational Site	Crowley	Louisiana
United States	Allakos Investigational Site	Danville	Pennsylvania
United States	Allakos Investigational Site	Dayton	Ohio
United States	Allakos Investigational Site	Durham	North Carolina
United States	Allakos Investigational Site	Edgewater	Florida
United States	Allakos Investigational Site	Fairfax	Virginia
United States	Allakos Investigational Site	Gilbert	Arizona
United States	Allakos Investigational Site	Great Neck	New York
United States	Allakos Investigational Site	Hixson	Tennessee
United States	Allakos Investigational Site	Houston	Texas
United States	Allakos Investigational Site	Huntsville	Alabama
United States	Allakos Investigational Site	Jacksonville	Florida
United States	Allakos Investigational Site	Kansas City	Missouri
United States	Allakos Investigational Site	Kingsport	Tennessee
United States	Allakos Investigational Site	La Jolla	California
United States	Allakos Investigational Site	Las Vegas	Nevada
United States	Allakos Investigational Site	Little Rock	Arkansas
United States	Allakos Investigational Site	Mentor	Ohio
United States	Allakos Investigational Site	Miami	Florida
United States	Allakos Investigational Site	Murrieta	California
United States	Allakos Investigational Site	Nashville	Tennessee
United States	Allakos Investigational Site	New Port Richey	Florida
United States	Allakos Investigational Site	New York	New York
United States	Allakos Investigational Site	Oakland	California
United States	Allakos Investigational Site	Ogden	Utah
United States	Allakos Investigational Site	Oklahoma City	Oklahoma
United States	Allakos Investigational Site	Philadelphia	Pennsylvania
United States	Allakos Investigational Site	Phoenix	Arizona
United States	Allakos Investigational Site	Reno	Nevada
United States	Allakos Investigational Site	Riverton	Utah
United States	Allakos Investigational Site	Rochester	Minnesota
United States	Allakos Investigational Site	Rocky Mount	North Carolina
United States	Allakos Investigational Site	Salt Lake City	Utah
United States	Allakos Investigational Site	Sandy	Utah
United States	Allakos Investigational Site	Santa Monica	California
United States	Allakos Investigational Site	Scottsdale	Arizona
United States	Allakos Investigational Site	Spokane	Washington
United States	Allakos Investigational Site	Tustin	California
United States	Allakos Investigational Site	Ventura	California
United States	Allakos Investigational Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Allakos Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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